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id="social-redesign-work-container"><div class="upload-header"><h2 class="ds2-5-heading-sans-serif-xs">Uploads</h2></div><div class="documents-container backbone-social-profile-documents" style="width: 100%;"><div class="u-taCenter"></div><div class="profile--tab_content_container js-tab-pane tab-pane active" id="all"><div class="profile--tab_heading_container js-section-heading" data-section="Papers" id="Papers"><h3 class="profile--tab_heading_container">Papers by Joana Tavares</h3></div><div class="js-work-strip profile--work_container" data-work-id="7143049"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143049/Differential_effects_of_polyamine_derivative_compounds_against_Leishmania_infantum_promastigotes_and_axenic_amastigotes"><img alt="Research paper thumbnail of Differential effects of polyamine derivative compounds against Leishmania infantum promastigotes and axenic amastigotes" class="work-thumbnail" src="https://attachments.academia-assets.com/48583896/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143049/Differential_effects_of_polyamine_derivative_compounds_against_Leishmania_infantum_promastigotes_and_axenic_amastigotes">Differential effects of polyamine derivative compounds against Leishmania infantum promastigotes and axenic amastigotes</a></div><div class="wp-workCard_item"><span>International Journal for Parasitology</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The natural polyamines are ubiquitous polycationic compounds that play important biological funct...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The natural polyamines are ubiquitous polycationic compounds that play important biological functions in cell growth and differentiation. In the case of protozoan species that are causative agents of important human diseases such as Leishmaniasis, an exogenous supply of polyamines supports parasite proliferation. In the present study, we have investigated the effect of three polyamine derivatives, (namely bisnaphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd) and spermine (BNIPSpm)), on the proliferative stages of Leishmania infantum, the causative agent of visceral leishmaniasis in the Mediterranean basin. A significant reduction of promastigotes and axenic amastigotes growth was observed in the presence of increasing concentrations of the drugs, although the mechanisms leading to the parasite growth arrest seems to be different. Indeed, by using a number of biochemical approaches to analyse the alterations that occurred during early stages of parasite-drug interaction (i.e. membrane phosphatidylserine exposure measured by annexin V binding, DNA fragmentation, deoxynucleotidyltranferase-mediated dUTP end labelin (TUNEL), mitochondrial transmembrane potential loss), we showed that the drugs had the capacity to induce the death of promastigotes by a mechanism that shares many features with metazoan apoptosis. Surprisingly, the amastigotes did not behave in a similar way to promastigotes. The drug inhibitory effect on amastigotes growth and the absence of propidium iodide labelling may suggest that the compounds are acting as cytostatic substances. Although, the mechanisms of action of these compounds have yet to be elucidated, the above data show for the first time that polyamine derivatives may act differentially on the Leishmania parasite stages. Further chemical modifications are needed to make the polyamine derivatives as well as other analogues able to target the amastigote stage of the parasite. q</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="4794fb7e519060791c6f32ccf48ecb89" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583896,"asset_id":7143049,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583896/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143049"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143049"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143049; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143049]").text(description); $(".js-view-count[data-work-id=7143049]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143049; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143049']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143049, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "4794fb7e519060791c6f32ccf48ecb89" } } $('.js-work-strip[data-work-id=7143049]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143049,"title":"Differential effects of polyamine derivative compounds against Leishmania infantum promastigotes and axenic amastigotes","translated_title":"","metadata":{"grobid_abstract":"The natural polyamines are ubiquitous polycationic compounds that play important biological functions in cell growth and differentiation. 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In the case of protozoan species that are causative agents of important human diseases such as Leishmaniasis, an exogenous supply of polyamines supports parasite proliferation. In the present study, we have investigated the effect of three polyamine derivatives, (namely bisnaphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd) and spermine (BNIPSpm)), on the proliferative stages of Leishmania infantum, the causative agent of visceral leishmaniasis in the Mediterranean basin. A significant reduction of promastigotes and axenic amastigotes growth was observed in the presence of increasing concentrations of the drugs, although the mechanisms leading to the parasite growth arrest seems to be different. Indeed, by using a number of biochemical approaches to analyse the alterations that occurred during early stages of parasite-drug interaction (i.e. membrane phosphatidylserine exposure measured by annexin V binding, DNA fragmentation, deoxynucleotidyltranferase-mediated dUTP end labelin (TUNEL), mitochondrial transmembrane potential loss), we showed that the drugs had the capacity to induce the death of promastigotes by a mechanism that shares many features with metazoan apoptosis. Surprisingly, the amastigotes did not behave in a similar way to promastigotes. The drug inhibitory effect on amastigotes growth and the absence of propidium iodide labelling may suggest that the compounds are acting as cytostatic substances. Although, the mechanisms of action of these compounds have yet to be elucidated, the above data show for the first time that polyamine derivatives may act differentially on the Leishmania parasite stages. Further chemical modifications are needed to make the polyamine derivatives as well as other analogues able to target the amastigote stage of the parasite. q","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583896,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583896/thumbnails/1.jpg","file_name":"j.ijpara.2005.01.00820160905-16660-3tgl77.pdf","download_url":"https://www.academia.edu/attachments/48583896/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Differential_effects_of_polyamine_deriva.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583896/j.ijpara.2005.01.00820160905-16660-3tgl77-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DDifferential_effects_of_polyamine_deriva.pdf\u0026Expires=1736775918\u0026Signature=g0j~katLqyz8RyztxYX1ADIx0m0MnWzkcpqiQrHXtWg89jNuGsQN8Ugm7cABuVwAOIK3ShhBv-ckXIXNtUJ~k~xhaLzDyfb~Uo3FlxrTgzQMqkFUHFpSfCLHLqH7bT8kCwn0R7EAEPD9wVnRV-sNIW1KQ-VZPfbTZ5Cp4yoAPyQYrTM7pqgfPhsSs1L9imHrjhREoLDfCkOjlplSOSUo81Mizu71j~hgPtSSWxhmmmo6G7wH1PnYDW5FZmSo9sdHGuKQ465aWLblggN5zVLmPX4~Z-cSP5ZTCErvfGM4vdOW5rtlbfzL2uXnE~vfkV7Lxdp13UMrkxgtwvWFDTGc7w__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":159,"name":"Microbiology","url":"https://www.academia.edu/Documents/in/Microbiology"},{"id":173,"name":"Zoology","url":"https://www.academia.edu/Documents/in/Zoology"},{"id":6599,"name":"Flow Cytometry","url":"https://www.academia.edu/Documents/in/Flow_Cytometry"},{"id":15719,"name":"Mitochondria","url":"https://www.academia.edu/Documents/in/Mitochondria"},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis"},{"id":83972,"name":"Permeability","url":"https://www.academia.edu/Documents/in/Permeability"},{"id":128004,"name":"Visceral Leishmaniasis","url":"https://www.academia.edu/Documents/in/Visceral_Leishmaniasis"},{"id":195950,"name":"Quinolones","url":"https://www.academia.edu/Documents/in/Quinolones"},{"id":323597,"name":"Fluorescent Antibody Technique","url":"https://www.academia.edu/Documents/in/Fluorescent_Antibody_Technique"},{"id":421780,"name":"Putrescine","url":"https://www.academia.edu/Documents/in/Putrescine"},{"id":421781,"name":"Spermine","url":"https://www.academia.edu/Documents/in/Spermine"},{"id":421782,"name":"Spermidine","url":"https://www.academia.edu/Documents/in/Spermidine"},{"id":537505,"name":"For","url":"https://www.academia.edu/Documents/in/For"},{"id":644860,"name":"Veterinary Sciences","url":"https://www.academia.edu/Documents/in/Veterinary_Sciences"},{"id":725615,"name":"Mechanism of action","url":"https://www.academia.edu/Documents/in/Mechanism_of_action"},{"id":789996,"name":"Leishmania infantum","url":"https://www.academia.edu/Documents/in/Leishmania_infantum"},{"id":833228,"name":"Human Disease","url":"https://www.academia.edu/Documents/in/Human_Disease"},{"id":966608,"name":"Mediterranean Basin","url":"https://www.academia.edu/Documents/in/Mediterranean_Basin"},{"id":979632,"name":"Drug Interaction","url":"https://www.academia.edu/Documents/in/Drug_Interaction"},{"id":1335154,"name":"Propidium Iodide","url":"https://www.academia.edu/Documents/in/Propidium_Iodide"},{"id":1418721,"name":"Chemical Modification","url":"https://www.academia.edu/Documents/in/Chemical_Modification"},{"id":1954130,"name":"Cell Growth","url":"https://www.academia.edu/Documents/in/Cell_Growth"},{"id":2256666,"name":"DNA fragmentation","url":"https://www.academia.edu/Documents/in/DNA_fragmentation"}],"urls":[{"id":2945792,"url":"http://www.sciencedirect.com/science/article/pii/S0020751905000391"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143048"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143048/Impact_of_Continuous_Axenic_Cultivation_in_Leishmania_infantum_Virulence"><img alt="Research paper thumbnail of Impact of Continuous Axenic Cultivation in Leishmania infantum Virulence" class="work-thumbnail" src="https://attachments.academia-assets.com/48583915/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143048/Impact_of_Continuous_Axenic_Cultivation_in_Leishmania_infantum_Virulence">Impact of Continuous Axenic Cultivation in Leishmania infantum Virulence</a></div><div class="wp-workCard_item"><span>PLOS Neglected Tropical Diseases</span><span>, 2012</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Experimental infections with visceral Leishmania spp. are frequently performed referring to stati...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Experimental infections with visceral Leishmania spp. are frequently performed referring to stationary parasite cultures that are comprised of a mixture of metacyclic and non-metacyclic parasites often with little regard to time of culture and metacyclic purification. This may lead to misleading or irreproducible experimental data. It is known that the maintenance of Leishmania spp. in vitro results in a progressive loss of virulence that can be reverted by passage in a mammalian host. In the present study, we aimed to characterize the loss of virulence in culture comparing the in vitro and in vivo infection and immunological profile of L. infantum stationary promastigotes submitted to successive periods of in vitro cultivation. To evaluate the effect of axenic in vitro culture in parasite virulence, we submitted L. infantum promastigotes to 4, 21 or 31 successive in vitro passages. Our results demonstrated a rapid and significant loss of parasite virulence when parasites are sustained in axenic culture. Strikingly, the parasite capacity to modulate macrophage activation decreased significantly with the augmentation of the number of in vitro passages. We validated these in vitro observations using an experimental murine model of infection. A significant correlation was found between higher parasite burdens and lower number of in vitro passages in infected Balb/c mice. Furthermore, we have demonstrated that the virulence deficit caused by successive in vitro passages results from an inadequate capacity to differentiate into amastigote forms. In conclusion, our data demonstrated that the use of parasites with distinct periods of axenic in vitro culture induce distinct infection rates and immunological responses and correlated this phenotype with a rapid loss of promastigote differentiation capacity. These results highlight the need for a standard operating protocol (SOP) when studying Leishmania species.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="6a9c6d129ead05d2d3bdd30be4d0ba51" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583915,"asset_id":7143048,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583915/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143048"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143048"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143048; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143048]").text(description); $(".js-view-count[data-work-id=7143048]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143048; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143048']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143048, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "6a9c6d129ead05d2d3bdd30be4d0ba51" } } $('.js-work-strip[data-work-id=7143048]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143048,"title":"Impact of Continuous Axenic Cultivation in Leishmania infantum Virulence","translated_title":"","metadata":{"grobid_abstract":"Experimental infections with visceral Leishmania spp. are frequently performed referring to stationary parasite cultures that are comprised of a mixture of metacyclic and non-metacyclic parasites often with little regard to time of culture and metacyclic purification. This may lead to misleading or irreproducible experimental data. It is known that the maintenance of Leishmania spp. in vitro results in a progressive loss of virulence that can be reverted by passage in a mammalian host. In the present study, we aimed to characterize the loss of virulence in culture comparing the in vitro and in vivo infection and immunological profile of L. infantum stationary promastigotes submitted to successive periods of in vitro cultivation. To evaluate the effect of axenic in vitro culture in parasite virulence, we submitted L. infantum promastigotes to 4, 21 or 31 successive in vitro passages. Our results demonstrated a rapid and significant loss of parasite virulence when parasites are sustained in axenic culture. Strikingly, the parasite capacity to modulate macrophage activation decreased significantly with the augmentation of the number of in vitro passages. We validated these in vitro observations using an experimental murine model of infection. A significant correlation was found between higher parasite burdens and lower number of in vitro passages in infected Balb/c mice. Furthermore, we have demonstrated that the virulence deficit caused by successive in vitro passages results from an inadequate capacity to differentiate into amastigote forms. In conclusion, our data demonstrated that the use of parasites with distinct periods of axenic in vitro culture induce distinct infection rates and immunological responses and correlated this phenotype with a rapid loss of promastigote differentiation capacity. These results highlight the need for a standard operating protocol (SOP) when studying Leishmania species.","publication_date":{"day":null,"month":null,"year":2012,"errors":{}},"publication_name":"PLOS Neglected Tropical Diseases","grobid_abstract_attachment_id":48583915},"translated_abstract":null,"internal_url":"https://www.academia.edu/7143048/Impact_of_Continuous_Axenic_Cultivation_in_Leishmania_infantum_Virulence","translated_internal_url":"","created_at":"2014-05-24T01:01:51.436-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583915,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583915/thumbnails/1.jpg","file_name":"Impact_of_continuous_axenic_cultivation_20160905-23542-g1leo1.pdf","download_url":"https://www.academia.edu/attachments/48583915/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Impact_of_Continuous_Axenic_Cultivation.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583915/Impact_of_continuous_axenic_cultivation_20160905-23542-g1leo1-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DImpact_of_Continuous_Axenic_Cultivation.pdf\u0026Expires=1736775918\u0026Signature=N3xajqY2-01Y1hhRgV3FNknhovcYgB9lbw8Yn2Jk4J-DwsiRUT~ZsodOogaWf9Vh1aCZIgI5rlQ4~fFfAMugjgm9NbdiR0rGPgmUuSvd5eD0Py9WpVcW3iCbl49lO5EvFOXLOhbNxcosbRDJ02xjzfR6LFWr5MDDF-BSNXvZXMmpHReRG0ePlkzbeqLYmUxt7AVJ9I5BgMVQ6E8yg50d-kw9B1v9t3z~~mdCYmi2tlMsmMbt03CFY5gh1IoOmQgfUuL~FeJPdEr9NE6c-c6qLqwRBw9saBaz~~3C2Qm7U0zTEzwYGiYKoB0twMcSbm~cSklKKkmPPjusF4oqfHOhdA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Impact_of_Continuous_Axenic_Cultivation_in_Leishmania_infantum_Virulence","translated_slug":"","page_count":12,"language":"en","content_type":"Work","summary":"Experimental infections with visceral Leishmania spp. are frequently performed referring to stationary parasite cultures that are comprised of a mixture of metacyclic and non-metacyclic parasites often with little regard to time of culture and metacyclic purification. This may lead to misleading or irreproducible experimental data. It is known that the maintenance of Leishmania spp. in vitro results in a progressive loss of virulence that can be reverted by passage in a mammalian host. In the present study, we aimed to characterize the loss of virulence in culture comparing the in vitro and in vivo infection and immunological profile of L. infantum stationary promastigotes submitted to successive periods of in vitro cultivation. To evaluate the effect of axenic in vitro culture in parasite virulence, we submitted L. infantum promastigotes to 4, 21 or 31 successive in vitro passages. Our results demonstrated a rapid and significant loss of parasite virulence when parasites are sustained in axenic culture. Strikingly, the parasite capacity to modulate macrophage activation decreased significantly with the augmentation of the number of in vitro passages. We validated these in vitro observations using an experimental murine model of infection. A significant correlation was found between higher parasite burdens and lower number of in vitro passages in infected Balb/c mice. Furthermore, we have demonstrated that the virulence deficit caused by successive in vitro passages results from an inadequate capacity to differentiate into amastigote forms. In conclusion, our data demonstrated that the use of parasites with distinct periods of axenic in vitro culture induce distinct infection rates and immunological responses and correlated this phenotype with a rapid loss of promastigote differentiation capacity. These results highlight the need for a standard operating protocol (SOP) when studying Leishmania species.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583915,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583915/thumbnails/1.jpg","file_name":"Impact_of_continuous_axenic_cultivation_20160905-23542-g1leo1.pdf","download_url":"https://www.academia.edu/attachments/48583915/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Impact_of_Continuous_Axenic_Cultivation.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583915/Impact_of_continuous_axenic_cultivation_20160905-23542-g1leo1-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DImpact_of_Continuous_Axenic_Cultivation.pdf\u0026Expires=1736775918\u0026Signature=N3xajqY2-01Y1hhRgV3FNknhovcYgB9lbw8Yn2Jk4J-DwsiRUT~ZsodOogaWf9Vh1aCZIgI5rlQ4~fFfAMugjgm9NbdiR0rGPgmUuSvd5eD0Py9WpVcW3iCbl49lO5EvFOXLOhbNxcosbRDJ02xjzfR6LFWr5MDDF-BSNXvZXMmpHReRG0ePlkzbeqLYmUxt7AVJ9I5BgMVQ6E8yg50d-kw9B1v9t3z~~mdCYmi2tlMsmMbt03CFY5gh1IoOmQgfUuL~FeJPdEr9NE6c-c6qLqwRBw9saBaz~~3C2Qm7U0zTEzwYGiYKoB0twMcSbm~cSklKKkmPPjusF4oqfHOhdA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":17491,"name":"Macrophages","url":"https://www.academia.edu/Documents/in/Macrophages"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":52873,"name":"Virulence","url":"https://www.academia.edu/Documents/in/Virulence"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":128004,"name":"Visceral Leishmaniasis","url":"https://www.academia.edu/Documents/in/Visceral_Leishmaniasis"},{"id":238630,"name":"Experimental Infection","url":"https://www.academia.edu/Documents/in/Experimental_Infection"},{"id":413750,"name":"In vitro culture","url":"https://www.academia.edu/Documents/in/In_vitro_culture"},{"id":789996,"name":"Leishmania infantum","url":"https://www.academia.edu/Documents/in/Leishmania_infantum"},{"id":951639,"name":"Murine Model","url":"https://www.academia.edu/Documents/in/Murine_Model"},{"id":1120502,"name":"Experimental Data","url":"https://www.academia.edu/Documents/in/Experimental_Data"}],"urls":[{"id":2945791,"url":"http://dx.doi.org/10.1371/journal.pntd.0001469"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143047"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143047/Leishmania_cytosolic_silent_information_regulatory_protein_2_deacetylase_induces_murine_B_cell_differentiation_and_in_vivo_production_of_specific_antibodies"><img alt="Research paper thumbnail of Leishmania cytosolic silent information regulatory protein 2 deacetylase induces murine B-cell differentiation and in vivo production of specific antibodies" class="work-thumbnail" src="https://attachments.academia-assets.com/48583901/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143047/Leishmania_cytosolic_silent_information_regulatory_protein_2_deacetylase_induces_murine_B_cell_differentiation_and_in_vivo_production_of_specific_antibodies">Leishmania cytosolic silent information regulatory protein 2 deacetylase induces murine B-cell differentiation and in vivo production of specific antibodies</a></div><div class="wp-workCard_item"><span>Immunology</span><span>, 2006</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">In previous studies, we identified a gene product belonging to the silent information regulatory ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">In previous studies, we identified a gene product belonging to the silent information regulatory 2 protein (SIR2) family. This protein is expressed by all Leishmania species so far examined (L. major, L. infantum, L. amazonensis, L. mexicana) and found to be crucial for parasite survival and virulence. In the present study, we investigated whether a Leishmania SIR2 recombinant protein (LmSIR2) would affect T- and B-cell functions in a murine model. In vitro treatment of spleen cells from normal BALB/c mice with LmSIR2 showed increased expression of CD69 on B cells. This effect was not abolished by the addition of polymyxin B. Intravenous injection of LmSIR2 into BALB/c mice induced increased spleen B cell number by a factor of about ≈1·6, whereas no modification occurred at the level of CD4+ and CD8+ cells. Furthermore, intraperitoneal injection of LmSIR2 alone without adjuvant into BALB/c mice or nude mice triggered the production of elevated levels of LmSIR2-specific antibodies. The analysis of specific isotype profiles showed a predominance of immunoglobulin G1 (IgG1) and IgG2a antibody responses in BALB/c mice, and IgM in nude mice. Moreover, the anti-LmSIR2 mouse antibodies in the presence of complement induced the in vitro lysis of L. infantum amastigotes. In the absence of complement, the antibodies induced significant inhibition of amastigotes developpement inside macrophages. Together, the current study provides the first evidence that a Leishmania protein belonging to the SIR2 family may play a role in the regulation of immune response through its capacity to trigger B-cell effector function.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="2ab547e26b2268331e1f58530be4c186" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583901,"asset_id":7143047,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583901/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143047"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143047"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143047; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143047]").text(description); $(".js-view-count[data-work-id=7143047]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143047; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143047']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143047, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "2ab547e26b2268331e1f58530be4c186" } } $('.js-work-strip[data-work-id=7143047]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143047,"title":"Leishmania cytosolic silent information regulatory protein 2 deacetylase induces murine B-cell differentiation and in vivo production of specific antibodies","translated_title":"","metadata":{"abstract":"In previous studies, we identified a gene product belonging to the silent information regulatory 2 protein (SIR2) family. This protein is expressed by all Leishmania species so far examined (L. major, L. infantum, L. amazonensis, L. mexicana) and found to be crucial for parasite survival and virulence. In the present study, we investigated whether a Leishmania SIR2 recombinant protein (LmSIR2) would affect T- and B-cell functions in a murine model. In vitro treatment of spleen cells from normal BALB/c mice with LmSIR2 showed increased expression of CD69 on B cells. This effect was not abolished by the addition of polymyxin B. Intravenous injection of LmSIR2 into BALB/c mice induced increased spleen B cell number by a factor of about ≈1·6, whereas no modification occurred at the level of CD4+ and CD8+ cells. Furthermore, intraperitoneal injection of LmSIR2 alone without adjuvant into BALB/c mice or nude mice triggered the production of elevated levels of LmSIR2-specific antibodies. The analysis of specific isotype profiles showed a predominance of immunoglobulin G1 (IgG1) and IgG2a antibody responses in BALB/c mice, and IgM in nude mice. Moreover, the anti-LmSIR2 mouse antibodies in the presence of complement induced the in vitro lysis of L. infantum amastigotes. In the absence of complement, the antibodies induced significant inhibition of amastigotes developpement inside macrophages. Together, the current study provides the first evidence that a Leishmania protein belonging to the SIR2 family may play a role in the regulation of immune response through its capacity to trigger B-cell effector function.","publication_date":{"day":null,"month":null,"year":2006,"errors":{}},"publication_name":"Immunology"},"translated_abstract":"In previous studies, we identified a gene product belonging to the silent information regulatory 2 protein (SIR2) family. This protein is expressed by all Leishmania species so far examined (L. major, L. infantum, L. amazonensis, L. mexicana) and found to be crucial for parasite survival and virulence. In the present study, we investigated whether a Leishmania SIR2 recombinant protein (LmSIR2) would affect T- and B-cell functions in a murine model. In vitro treatment of spleen cells from normal BALB/c mice with LmSIR2 showed increased expression of CD69 on B cells. This effect was not abolished by the addition of polymyxin B. Intravenous injection of LmSIR2 into BALB/c mice induced increased spleen B cell number by a factor of about ≈1·6, whereas no modification occurred at the level of CD4+ and CD8+ cells. Furthermore, intraperitoneal injection of LmSIR2 alone without adjuvant into BALB/c mice or nude mice triggered the production of elevated levels of LmSIR2-specific antibodies. The analysis of specific isotype profiles showed a predominance of immunoglobulin G1 (IgG1) and IgG2a antibody responses in BALB/c mice, and IgM in nude mice. Moreover, the anti-LmSIR2 mouse antibodies in the presence of complement induced the in vitro lysis of L. infantum amastigotes. In the absence of complement, the antibodies induced significant inhibition of amastigotes developpement inside macrophages. Together, the current study provides the first evidence that a Leishmania protein belonging to the SIR2 family may play a role in the regulation of immune response through its capacity to trigger B-cell effector function.","internal_url":"https://www.academia.edu/7143047/Leishmania_cytosolic_silent_information_regulatory_protein_2_deacetylase_induces_murine_B_cell_differentiation_and_in_vivo_production_of_specific_antibodies","translated_internal_url":"","created_at":"2014-05-24T01:01:51.146-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583901,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583901/thumbnails/1.jpg","file_name":"Leishmania_cytosolic_silent_information_20160905-30311-wsiq48.pdf","download_url":"https://www.academia.edu/attachments/48583901/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Leishmania_cytosolic_silent_information.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583901/Leishmania_cytosolic_silent_information_20160905-30311-wsiq48-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DLeishmania_cytosolic_silent_information.pdf\u0026Expires=1736775918\u0026Signature=EBm~FMwsIEHkOsUJ30pdRH9mIHJjKBhER5MwE--c26bphdihcDeWYu0wyrGoilqI6HcMn1NKQJ0At~ePuVlwt4w6vlxEpeshiar5RlTdJqU7UE~AGsCNV1ZAEOPZsyqporQP3zKlVRDVUMWvoPM2sXdZUFeLN~s1BC~7OqF8x-WPrs1l-Dkh1Dt-53aV9RYq4eKJv-ClwrHkFKyQMxWGC~LyBh4hle-65UMzSPsqMvUpcnsfd4I6FUxmM3m1BAIzEQGaiiupDV4UIPzkpk2WuzxHtrvHVYyWMWEqfHMb8OO0ywDFSQ8GGOKWLGTyJRXtCcTEC5udqTwOYCrAGy5-Iw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Leishmania_cytosolic_silent_information_regulatory_protein_2_deacetylase_induces_murine_B_cell_differentiation_and_in_vivo_production_of_specific_antibodies","translated_slug":"","page_count":12,"language":"en","content_type":"Work","summary":"In previous studies, we identified a gene product belonging to the silent information regulatory 2 protein (SIR2) family. This protein is expressed by all Leishmania species so far examined (L. major, L. infantum, L. amazonensis, L. mexicana) and found to be crucial for parasite survival and virulence. In the present study, we investigated whether a Leishmania SIR2 recombinant protein (LmSIR2) would affect T- and B-cell functions in a murine model. In vitro treatment of spleen cells from normal BALB/c mice with LmSIR2 showed increased expression of CD69 on B cells. This effect was not abolished by the addition of polymyxin B. Intravenous injection of LmSIR2 into BALB/c mice induced increased spleen B cell number by a factor of about ≈1·6, whereas no modification occurred at the level of CD4+ and CD8+ cells. Furthermore, intraperitoneal injection of LmSIR2 alone without adjuvant into BALB/c mice or nude mice triggered the production of elevated levels of LmSIR2-specific antibodies. The analysis of specific isotype profiles showed a predominance of immunoglobulin G1 (IgG1) and IgG2a antibody responses in BALB/c mice, and IgM in nude mice. Moreover, the anti-LmSIR2 mouse antibodies in the presence of complement induced the in vitro lysis of L. infantum amastigotes. In the absence of complement, the antibodies induced significant inhibition of amastigotes developpement inside macrophages. Together, the current study provides the first evidence that a Leishmania protein belonging to the SIR2 family may play a role in the regulation of immune response through its capacity to trigger B-cell effector function.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583901,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583901/thumbnails/1.jpg","file_name":"Leishmania_cytosolic_silent_information_20160905-30311-wsiq48.pdf","download_url":"https://www.academia.edu/attachments/48583901/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Leishmania_cytosolic_silent_information.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583901/Leishmania_cytosolic_silent_information_20160905-30311-wsiq48-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DLeishmania_cytosolic_silent_information.pdf\u0026Expires=1736775918\u0026Signature=EBm~FMwsIEHkOsUJ30pdRH9mIHJjKBhER5MwE--c26bphdihcDeWYu0wyrGoilqI6HcMn1NKQJ0At~ePuVlwt4w6vlxEpeshiar5RlTdJqU7UE~AGsCNV1ZAEOPZsyqporQP3zKlVRDVUMWvoPM2sXdZUFeLN~s1BC~7OqF8x-WPrs1l-Dkh1Dt-53aV9RYq4eKJv-ClwrHkFKyQMxWGC~LyBh4hle-65UMzSPsqMvUpcnsfd4I6FUxmM3m1BAIzEQGaiiupDV4UIPzkpk2WuzxHtrvHVYyWMWEqfHMb8OO0ywDFSQ8GGOKWLGTyJRXtCcTEC5udqTwOYCrAGy5-Iw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":1290,"name":"Immunology","url":"https://www.academia.edu/Documents/in/Immunology"},{"id":17491,"name":"Macrophages","url":"https://www.academia.edu/Documents/in/Macrophages"},{"id":49018,"name":"Spleen","url":"https://www.academia.edu/Documents/in/Spleen"},{"id":60436,"name":"Cell Differentiation","url":"https://www.academia.edu/Documents/in/Cell_Differentiation"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":208178,"name":"Sirtuins","url":"https://www.academia.edu/Documents/in/Sirtuins"},{"id":678853,"name":"B Lymphocytes","url":"https://www.academia.edu/Documents/in/B_Lymphocytes"},{"id":744838,"name":"Protozoan Proteins","url":"https://www.academia.edu/Documents/in/Protozoan_Proteins"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation"},{"id":789996,"name":"Leishmania infantum","url":"https://www.academia.edu/Documents/in/Leishmania_infantum"},{"id":990417,"name":"Recombinant Proteins","url":"https://www.academia.edu/Documents/in/Recombinant_Proteins"},{"id":1272906,"name":"Enzyme Linked Immunosorbent Assay","url":"https://www.academia.edu/Documents/in/Enzyme_Linked_Immunosorbent_Assay"},{"id":1716403,"name":"immunoglobulin G","url":"https://www.academia.edu/Documents/in/immunoglobulin_G"}],"urls":[{"id":2945790,"url":"http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2567.2006.02468.x"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143046"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143046/Immunological_alterations_induced_by_polyamine_derivatives_on_murine_splenocytes_and_human_mononuclear_cells"><img alt="Research paper thumbnail of Immunological alterations induced by polyamine derivatives on murine splenocytes and human mononuclear cells" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143046/Immunological_alterations_induced_by_polyamine_derivatives_on_murine_splenocytes_and_human_mononuclear_cells">Immunological alterations induced by polyamine derivatives on murine splenocytes and human mononuclear cells</a></div><div class="wp-workCard_item"><span>International Immunopharmacology</span><span>, 2004</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Three polyamine derivatives assigned as bis-naphthalimidopropyl putrescine (BNIPPut), spermidine ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Three polyamine derivatives assigned as bis-naphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd) and spermine (BNIPSpm) were studied to determine their effects on the proliferation of murine splenocytes and human peripheral blood mononuclear cells (PBMC) induced by the mitogens, Con A, LPS and PHA. All compounds showed a dose dependent inhibitory effect on mouse and human T cell proliferation induced by the mitogens, with BNIPPut exhibiting the most potent antiproliferative activity, followed by BNIPSpd and by BNIPSpm, respectively (Put &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Spd &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Spm), when considering human T cells. This suppressive activity also affects the capacity of mouse spleen cells to produce Th1 cytokines, namely IL-2 and INF-gamma after in vitro stimulation with Con A. The polyamine-induced inhibition also occurred in the case of LPS-stimulated B cells with a marked decrease of CD69 expression by these cells. Furthermore, the ability for these polyamine derivatives to induce apoptosis on Con A-stimulated splenocytes could be related to their antiproliferative activity.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143046"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143046"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143046; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143046]").text(description); $(".js-view-count[data-work-id=7143046]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143046; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143046']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143046, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=7143046]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143046,"title":"Immunological alterations induced by polyamine derivatives on murine splenocytes and human mononuclear cells","translated_title":"","metadata":{"abstract":"Three polyamine derivatives assigned as bis-naphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd) and spermine (BNIPSpm) were studied to determine their effects on the proliferation of murine splenocytes and human peripheral blood mononuclear cells (PBMC) induced by the mitogens, Con A, LPS and PHA. All compounds showed a dose dependent inhibitory effect on mouse and human T cell proliferation induced by the mitogens, with BNIPPut exhibiting the most potent antiproliferative activity, followed by BNIPSpd and by BNIPSpm, respectively (Put \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Spd \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Spm), when considering human T cells. This suppressive activity also affects the capacity of mouse spleen cells to produce Th1 cytokines, namely IL-2 and INF-gamma after in vitro stimulation with Con A. The polyamine-induced inhibition also occurred in the case of LPS-stimulated B cells with a marked decrease of CD69 expression by these cells. Furthermore, the ability for these polyamine derivatives to induce apoptosis on Con A-stimulated splenocytes could be related to their antiproliferative activity.","publication_date":{"day":null,"month":null,"year":2004,"errors":{}},"publication_name":"International Immunopharmacology"},"translated_abstract":"Three polyamine derivatives assigned as bis-naphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd) and spermine (BNIPSpm) were studied to determine their effects on the proliferation of murine splenocytes and human peripheral blood mononuclear cells (PBMC) induced by the mitogens, Con A, LPS and PHA. All compounds showed a dose dependent inhibitory effect on mouse and human T cell proliferation induced by the mitogens, with BNIPPut exhibiting the most potent antiproliferative activity, followed by BNIPSpd and by BNIPSpm, respectively (Put \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Spd \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Spm), when considering human T cells. This suppressive activity also affects the capacity of mouse spleen cells to produce Th1 cytokines, namely IL-2 and INF-gamma after in vitro stimulation with Con A. The polyamine-induced inhibition also occurred in the case of LPS-stimulated B cells with a marked decrease of CD69 expression by these cells. Furthermore, the ability for these polyamine derivatives to induce apoptosis on Con A-stimulated splenocytes could be related to their antiproliferative activity.","internal_url":"https://www.academia.edu/7143046/Immunological_alterations_induced_by_polyamine_derivatives_on_murine_splenocytes_and_human_mononuclear_cells","translated_internal_url":"","created_at":"2014-05-24T01:01:50.838-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Immunological_alterations_induced_by_polyamine_derivatives_on_murine_splenocytes_and_human_mononuclear_cells","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":"Three polyamine derivatives assigned as bis-naphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd) and spermine (BNIPSpm) were studied to determine their effects on the proliferation of murine splenocytes and human peripheral blood mononuclear cells (PBMC) induced by the mitogens, Con A, LPS and PHA. All compounds showed a dose dependent inhibitory effect on mouse and human T cell proliferation induced by the mitogens, with BNIPPut exhibiting the most potent antiproliferative activity, followed by BNIPSpd and by BNIPSpm, respectively (Put \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Spd \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Spm), when considering human T cells. This suppressive activity also affects the capacity of mouse spleen cells to produce Th1 cytokines, namely IL-2 and INF-gamma after in vitro stimulation with Con A. The polyamine-induced inhibition also occurred in the case of LPS-stimulated B cells with a marked decrease of CD69 expression by these cells. Furthermore, the ability for these polyamine derivatives to induce apoptosis on Con A-stimulated splenocytes could be related to their antiproliferative activity.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[],"research_interests":[{"id":6599,"name":"Flow Cytometry","url":"https://www.academia.edu/Documents/in/Flow_Cytometry"},{"id":9111,"name":"Cytokines","url":"https://www.academia.edu/Documents/in/Cytokines"},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis"},{"id":26699,"name":"Immunopharmacology","url":"https://www.academia.edu/Documents/in/Immunopharmacology"},{"id":49018,"name":"Spleen","url":"https://www.academia.edu/Documents/in/Spleen"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":195950,"name":"Quinolones","url":"https://www.academia.edu/Documents/in/Quinolones"},{"id":413195,"name":"Time Factors","url":"https://www.academia.edu/Documents/in/Time_Factors"},{"id":421782,"name":"Spermidine","url":"https://www.academia.edu/Documents/in/Spermidine"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation"},{"id":1272906,"name":"Enzyme Linked Immunosorbent Assay","url":"https://www.academia.edu/Documents/in/Enzyme_Linked_Immunosorbent_Assay"}],"urls":[{"id":2945789,"url":"http://www.sciencedirect.com/science/article/pii/S1567576904000608"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143044"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143044/The_Leishmania_infantum_cytosolic_SIR2_related_protein_1_LiSIR2RP1_is_an_NAD_dependent_deacetylase_and_ADP_ribosyltransferase"><img alt="Research paper thumbnail of The Leishmania infantum cytosolic SIR2-related protein 1 (LiSIR2RP1) is an NAD+-dependent deacetylase and ADP-ribosyltransferase" class="work-thumbnail" src="https://attachments.academia-assets.com/48583934/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143044/The_Leishmania_infantum_cytosolic_SIR2_related_protein_1_LiSIR2RP1_is_an_NAD_dependent_deacetylase_and_ADP_ribosyltransferase">The Leishmania infantum cytosolic SIR2-related protein 1 (LiSIR2RP1) is an NAD+-dependent deacetylase and ADP-ribosyltransferase</a></div><div class="wp-workCard_item"><span>Biochemical Journal</span><span>, 2008</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Proteins of the SIR2 (Silent Information Regulator 2) family are characterized by a conserved cat...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Proteins of the SIR2 (Silent Information Regulator 2) family are characterized by a conserved catalytic domain that exerts unique NAD + -dependent deacetylase activity on histones and various other cellular substrates. Previous reports from us have identified a Leishmania infantum gene encoding a cytosolic protein termed LiSIR2RP1 (Leishmania infantum SIR2-related protein 1) that belongs to the SIR2 family. Targeted disruption of one LiSIR2RP1 gene allele led to decreased amastigote virulence, in vitro as well as in vivo. In the present study, attempts were made for the first time to explore and characterize the enzymatic functions of LiSIR2RP1. The LiSIR2RP1 exhibited robust NAD + -dependent deacetylase and ADP-ribosyltransferase activities. Moreover, LiSIR2RP1 is capable of deacetylating tubulin, either in dimers or, when present, in taxol-stabilized microtubules or in promastigote and amastigote extracts. Furthermore, the immunostaining of parasites revealed a partial co-localization of α-tubulin and LiSIR2RP1 with punctate labelling, seen on the periphery of both promastigote and amastigote stages. Isolated parasite cyto-skeleton reacted with antibodies showed that part of LiSIR2RP1 is associated to the cytoskeleton network of both promastigote and amastigote forms. Moreover, the Western blot analysis of the soluble and insoluble fractions of the detergent of promastigote and amastigote forms revealed the presence of α-tubulin in the insoluble fraction, and the LiSIR2RP1 distributed in both soluble and insoluble fractions of promastigotes as well as amastigotes. Collectively, the results of the present study demonstrate that LiSIR2RP1 is an NAD + -dependent deacetylase that also exerts an ADP-ribosyltransferase activity. The fact that tubulin could be among the targets of LiSIR2RP1 may have significant implications during the remodelling of the morphology of the parasite and its interaction with the host cell.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="aa64525e1f18ae8c169db2dc9d2f33a4" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583934,"asset_id":7143044,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583934/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143044"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143044"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143044; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143044]").text(description); $(".js-view-count[data-work-id=7143044]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143044; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143044']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143044, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "aa64525e1f18ae8c169db2dc9d2f33a4" } } $('.js-work-strip[data-work-id=7143044]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143044,"title":"The Leishmania infantum cytosolic SIR2-related protein 1 (LiSIR2RP1) is an NAD+-dependent deacetylase and ADP-ribosyltransferase","translated_title":"","metadata":{"grobid_abstract":"Proteins of the SIR2 (Silent Information Regulator 2) family are characterized by a conserved catalytic domain that exerts unique NAD + -dependent deacetylase activity on histones and various other cellular substrates. Previous reports from us have identified a Leishmania infantum gene encoding a cytosolic protein termed LiSIR2RP1 (Leishmania infantum SIR2-related protein 1) that belongs to the SIR2 family. Targeted disruption of one LiSIR2RP1 gene allele led to decreased amastigote virulence, in vitro as well as in vivo. In the present study, attempts were made for the first time to explore and characterize the enzymatic functions of LiSIR2RP1. The LiSIR2RP1 exhibited robust NAD + -dependent deacetylase and ADP-ribosyltransferase activities. Moreover, LiSIR2RP1 is capable of deacetylating tubulin, either in dimers or, when present, in taxol-stabilized microtubules or in promastigote and amastigote extracts. Furthermore, the immunostaining of parasites revealed a partial co-localization of α-tubulin and LiSIR2RP1 with punctate labelling, seen on the periphery of both promastigote and amastigote stages. Isolated parasite cyto-skeleton reacted with antibodies showed that part of LiSIR2RP1 is associated to the cytoskeleton network of both promastigote and amastigote forms. Moreover, the Western blot analysis of the soluble and insoluble fractions of the detergent of promastigote and amastigote forms revealed the presence of α-tubulin in the insoluble fraction, and the LiSIR2RP1 distributed in both soluble and insoluble fractions of promastigotes as well as amastigotes. Collectively, the results of the present study demonstrate that LiSIR2RP1 is an NAD + -dependent deacetylase that also exerts an ADP-ribosyltransferase activity. The fact that tubulin could be among the targets of LiSIR2RP1 may have significant implications during the remodelling of the morphology of the parasite and its interaction with the host cell.","publication_date":{"day":null,"month":null,"year":2008,"errors":{}},"publication_name":"Biochemical Journal","grobid_abstract_attachment_id":48583934},"translated_abstract":null,"internal_url":"https://www.academia.edu/7143044/The_Leishmania_infantum_cytosolic_SIR2_related_protein_1_LiSIR2RP1_is_an_NAD_dependent_deacetylase_and_ADP_ribosyltransferase","translated_internal_url":"","created_at":"2014-05-24T01:01:50.535-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583934,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583934/thumbnails/1.jpg","file_name":"The_Leishmania_infantum_cytosolic_SIR2-r20160905-26881-qza57w.pdf","download_url":"https://www.academia.edu/attachments/48583934/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"The_Leishmania_infantum_cytosolic_SIR2_r.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583934/The_Leishmania_infantum_cytosolic_SIR2-r20160905-26881-qza57w-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DThe_Leishmania_infantum_cytosolic_SIR2_r.pdf\u0026Expires=1736775918\u0026Signature=MOoSzh-BjSfUTQsrcLIMc7Afzs7VQ8FFkPyBTJiJEwqJWBXuc-L624fJjv5KT5YSyW3RC-I65zz7ZGxr0qK~Bl64NMZSiS~i43RbdkpxLB0iCDKHkwJU2JMWxXh5ZOT~Mv1wD5Ck5QyEyUprK2x69ZyUAcInZ719E3nCT2NCx1vv8eoSRcelW0uofudqeCBLxYTE5agLNHTIyYMLuR-HkWrYjTovNkmVgKZLMaGwSJn34K7kHhzlAlwS3JBrKxfSU1Wpp8~MAbAtpp7MGAqO-MQrEOw8R6WpjdkZ7n0pqrNV0etytsTOAdKq13T7dz9OETTLXjSQ9Y-CSaPogbSfYQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"The_Leishmania_infantum_cytosolic_SIR2_related_protein_1_LiSIR2RP1_is_an_NAD_dependent_deacetylase_and_ADP_ribosyltransferase","translated_slug":"","page_count":10,"language":"en","content_type":"Work","summary":"Proteins of the SIR2 (Silent Information Regulator 2) family are characterized by a conserved catalytic domain that exerts unique NAD + -dependent deacetylase activity on histones and various other cellular substrates. Previous reports from us have identified a Leishmania infantum gene encoding a cytosolic protein termed LiSIR2RP1 (Leishmania infantum SIR2-related protein 1) that belongs to the SIR2 family. Targeted disruption of one LiSIR2RP1 gene allele led to decreased amastigote virulence, in vitro as well as in vivo. In the present study, attempts were made for the first time to explore and characterize the enzymatic functions of LiSIR2RP1. The LiSIR2RP1 exhibited robust NAD + -dependent deacetylase and ADP-ribosyltransferase activities. Moreover, LiSIR2RP1 is capable of deacetylating tubulin, either in dimers or, when present, in taxol-stabilized microtubules or in promastigote and amastigote extracts. Furthermore, the immunostaining of parasites revealed a partial co-localization of α-tubulin and LiSIR2RP1 with punctate labelling, seen on the periphery of both promastigote and amastigote stages. Isolated parasite cyto-skeleton reacted with antibodies showed that part of LiSIR2RP1 is associated to the cytoskeleton network of both promastigote and amastigote forms. Moreover, the Western blot analysis of the soluble and insoluble fractions of the detergent of promastigote and amastigote forms revealed the presence of α-tubulin in the insoluble fraction, and the LiSIR2RP1 distributed in both soluble and insoluble fractions of promastigotes as well as amastigotes. Collectively, the results of the present study demonstrate that LiSIR2RP1 is an NAD + -dependent deacetylase that also exerts an ADP-ribosyltransferase activity. The fact that tubulin could be among the targets of LiSIR2RP1 may have significant implications during the remodelling of the morphology of the parasite and its interaction with the host cell.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583934,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583934/thumbnails/1.jpg","file_name":"The_Leishmania_infantum_cytosolic_SIR2-r20160905-26881-qza57w.pdf","download_url":"https://www.academia.edu/attachments/48583934/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"The_Leishmania_infantum_cytosolic_SIR2_r.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583934/The_Leishmania_infantum_cytosolic_SIR2-r20160905-26881-qza57w-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DThe_Leishmania_infantum_cytosolic_SIR2_r.pdf\u0026Expires=1736775918\u0026Signature=MOoSzh-BjSfUTQsrcLIMc7Afzs7VQ8FFkPyBTJiJEwqJWBXuc-L624fJjv5KT5YSyW3RC-I65zz7ZGxr0qK~Bl64NMZSiS~i43RbdkpxLB0iCDKHkwJU2JMWxXh5ZOT~Mv1wD5Ck5QyEyUprK2x69ZyUAcInZ719E3nCT2NCx1vv8eoSRcelW0uofudqeCBLxYTE5agLNHTIyYMLuR-HkWrYjTovNkmVgKZLMaGwSJn34K7kHhzlAlwS3JBrKxfSU1Wpp8~MAbAtpp7MGAqO-MQrEOw8R6WpjdkZ7n0pqrNV0etytsTOAdKq13T7dz9OETTLXjSQ9Y-CSaPogbSfYQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":37508,"name":"Cytoskeleton","url":"https://www.academia.edu/Documents/in/Cytoskeleton"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":94271,"name":"Parasite","url":"https://www.academia.edu/Documents/in/Parasite"},{"id":176525,"name":"Biochemical","url":"https://www.academia.edu/Documents/in/Biochemical"},{"id":208178,"name":"Sirtuins","url":"https://www.academia.edu/Documents/in/Sirtuins"},{"id":260118,"name":"CHEMICAL SCIENCES","url":"https://www.academia.edu/Documents/in/CHEMICAL_SCIENCES"},{"id":533598,"name":"Tubulin","url":"https://www.academia.edu/Documents/in/Tubulin"},{"id":744838,"name":"Protozoan Proteins","url":"https://www.academia.edu/Documents/in/Protozoan_Proteins"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation"},{"id":789996,"name":"Leishmania infantum","url":"https://www.academia.edu/Documents/in/Leishmania_infantum"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival"}],"urls":[{"id":2945787,"url":"http://www.biochemj.org/bj/415/bj4150377.htm"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143043"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143043/Bisnaphthalimidopropyl_Derivatives_as_Inhibitors_of_Leishmania_SIR2_Related_Protein%C3%A2_1"><img alt="Research paper thumbnail of Bisnaphthalimidopropyl Derivatives as Inhibitors of Leishmania SIR2 Related Proteinâ 1" class="work-thumbnail" src="https://attachments.academia-assets.com/48583911/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143043/Bisnaphthalimidopropyl_Derivatives_as_Inhibitors_of_Leishmania_SIR2_Related_Protein%C3%A2_1">Bisnaphthalimidopropyl Derivatives as Inhibitors of Leishmania SIR2 Related Proteinâ 1</a></div><div class="wp-workCard_item"><span>Chemmedchem</span><span>, 2010</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The NAD+-dependent deacetylases, namely sirtuins, are involved in the regulation of a variety of ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The NAD+-dependent deacetylases, namely sirtuins, are involved in the regulation of a variety of biological processes such as gene silencing, DNA repair, longevity, metabolism, apoptosis, and development. An enzyme from the parasite Leishmania infantum that belongs to this family, LiSIR2RP1, is a NAD+-dependent tubulin deacetylase and an ADP-ribosyltransferase. This enzyme's involvement in L. infantum virulence and survival underscores its potential as a drug target. Our search for selective inhibitors of LiSIR2RP1 has led, for the first time, to the identification of the antiparasitic and anticancer bisnaphthalimidopropyl (BNIP) alkyl di- and triamines (IC50 values in the single-digit micromolar range for the most potent compounds). Structure–activity studies were conducted with 12 BNIP derivatives that differ in the length of the central alkyl chain, which links the two naphthalimidopropyl moieties. The most active and selective compound is the BNIP diaminononane (BNIPDanon), with IC50 values of 5.7 and 97.4 μM against the parasite and human forms (SIRT1) of the enzyme, respectively. Furthermore, this compound is an NAD+-competitive inhibitor that interacts differently with the parasite and human enzymes, as determined by docking analysis, which might explain its selectivity toward the parasitic enzyme.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="c0346087a5eb129102a51d1f7fa597d2" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583911,"asset_id":7143043,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583911/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143043"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143043"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143043; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143043]").text(description); $(".js-view-count[data-work-id=7143043]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143043; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143043']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143043, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "c0346087a5eb129102a51d1f7fa597d2" } } $('.js-work-strip[data-work-id=7143043]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143043,"title":"Bisnaphthalimidopropyl Derivatives as Inhibitors of Leishmania SIR2 Related Proteinâ 1","translated_title":"","metadata":{"abstract":"The NAD+-dependent deacetylases, namely sirtuins, are involved in the regulation of a variety of biological processes such as gene silencing, DNA repair, longevity, metabolism, apoptosis, and development. An enzyme from the parasite Leishmania infantum that belongs to this family, LiSIR2RP1, is a NAD+-dependent tubulin deacetylase and an ADP-ribosyltransferase. This enzyme's involvement in L. infantum virulence and survival underscores its potential as a drug target. Our search for selective inhibitors of LiSIR2RP1 has led, for the first time, to the identification of the antiparasitic and anticancer bisnaphthalimidopropyl (BNIP) alkyl di- and triamines (IC50 values in the single-digit micromolar range for the most potent compounds). Structure–activity studies were conducted with 12 BNIP derivatives that differ in the length of the central alkyl chain, which links the two naphthalimidopropyl moieties. The most active and selective compound is the BNIP diaminononane (BNIPDanon), with IC50 values of 5.7 and 97.4 μM against the parasite and human forms (SIRT1) of the enzyme, respectively. Furthermore, this compound is an NAD+-competitive inhibitor that interacts differently with the parasite and human enzymes, as determined by docking analysis, which might explain its selectivity toward the parasitic enzyme.","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"Chemmedchem"},"translated_abstract":"The NAD+-dependent deacetylases, namely sirtuins, are involved in the regulation of a variety of biological processes such as gene silencing, DNA repair, longevity, metabolism, apoptosis, and development. An enzyme from the parasite Leishmania infantum that belongs to this family, LiSIR2RP1, is a NAD+-dependent tubulin deacetylase and an ADP-ribosyltransferase. This enzyme's involvement in L. infantum virulence and survival underscores its potential as a drug target. Our search for selective inhibitors of LiSIR2RP1 has led, for the first time, to the identification of the antiparasitic and anticancer bisnaphthalimidopropyl (BNIP) alkyl di- and triamines (IC50 values in the single-digit micromolar range for the most potent compounds). Structure–activity studies were conducted with 12 BNIP derivatives that differ in the length of the central alkyl chain, which links the two naphthalimidopropyl moieties. The most active and selective compound is the BNIP diaminononane (BNIPDanon), with IC50 values of 5.7 and 97.4 μM against the parasite and human forms (SIRT1) of the enzyme, respectively. Furthermore, this compound is an NAD+-competitive inhibitor that interacts differently with the parasite and human enzymes, as determined by docking analysis, which might explain its selectivity toward the parasitic enzyme.","internal_url":"https://www.academia.edu/7143043/Bisnaphthalimidopropyl_Derivatives_as_Inhibitors_of_Leishmania_SIR2_Related_Protein%C3%A2_1","translated_internal_url":"","created_at":"2014-05-24T01:01:50.146-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583911,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583911/thumbnails/1.jpg","file_name":"Bisnaphthalimidopropyl_derivatives_as_in20160905-30903-yng3yz.pdf","download_url":"https://www.academia.edu/attachments/48583911/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Bisnaphthalimidopropyl_Derivatives_as_In.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583911/Bisnaphthalimidopropyl_derivatives_as_in20160905-30903-yng3yz-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DBisnaphthalimidopropyl_Derivatives_as_In.pdf\u0026Expires=1736775918\u0026Signature=X~erieiHVeEXtmLeepbMtL96rJC8LLDTfKDlxZILt9QTJ4ZMnplKtxLAYayzdZwjc~cWE~ZXTbF4glrDqlQpeVb9ICCgz9ej1VgVeDwnn~dZGRavkIPWfBYqoTeMejBOaCxtArhj4Alk~wQqDCBMeh~aytITULWF5iOPGDHcQcPszZlpZOcz992EVh7l21rsuU6kQpVlzKjIptoS4DhIUG41f7hRqOvx49voPE7chVtOPkm-4PlbXzASB1TWsO9tFtunsWJu1A8YIVd4TAEv7rcZ~Zz-VUO7rsDcTpNJZ4HLCbrKtd840LV2kYHiRIFawdAzNebASZ9UFwNxiRAoFg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Bisnaphthalimidopropyl_Derivatives_as_Inhibitors_of_Leishmania_SIR2_Related_Proteinâ_1","translated_slug":"","page_count":8,"language":"en","content_type":"Work","summary":"The NAD+-dependent deacetylases, namely sirtuins, are involved in the regulation of a variety of biological processes such as gene silencing, DNA repair, longevity, metabolism, apoptosis, and development. An enzyme from the parasite Leishmania infantum that belongs to this family, LiSIR2RP1, is a NAD+-dependent tubulin deacetylase and an ADP-ribosyltransferase. This enzyme's involvement in L. infantum virulence and survival underscores its potential as a drug target. Our search for selective inhibitors of LiSIR2RP1 has led, for the first time, to the identification of the antiparasitic and anticancer bisnaphthalimidopropyl (BNIP) alkyl di- and triamines (IC50 values in the single-digit micromolar range for the most potent compounds). Structure–activity studies were conducted with 12 BNIP derivatives that differ in the length of the central alkyl chain, which links the two naphthalimidopropyl moieties. The most active and selective compound is the BNIP diaminononane (BNIPDanon), with IC50 values of 5.7 and 97.4 μM against the parasite and human forms (SIRT1) of the enzyme, respectively. Furthermore, this compound is an NAD+-competitive inhibitor that interacts differently with the parasite and human enzymes, as determined by docking analysis, which might explain its selectivity toward the parasitic enzyme.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583911,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583911/thumbnails/1.jpg","file_name":"Bisnaphthalimidopropyl_derivatives_as_in20160905-30903-yng3yz.pdf","download_url":"https://www.academia.edu/attachments/48583911/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Bisnaphthalimidopropyl_Derivatives_as_In.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583911/Bisnaphthalimidopropyl_derivatives_as_in20160905-30903-yng3yz-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DBisnaphthalimidopropyl_Derivatives_as_In.pdf\u0026Expires=1736775918\u0026Signature=X~erieiHVeEXtmLeepbMtL96rJC8LLDTfKDlxZILt9QTJ4ZMnplKtxLAYayzdZwjc~cWE~ZXTbF4glrDqlQpeVb9ICCgz9ej1VgVeDwnn~dZGRavkIPWfBYqoTeMejBOaCxtArhj4Alk~wQqDCBMeh~aytITULWF5iOPGDHcQcPszZlpZOcz992EVh7l21rsuU6kQpVlzKjIptoS4DhIUG41f7hRqOvx49voPE7chVtOPkm-4PlbXzASB1TWsO9tFtunsWJu1A8YIVd4TAEv7rcZ~Zz-VUO7rsDcTpNJZ4HLCbrKtd840LV2kYHiRIFawdAzNebASZ9UFwNxiRAoFg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":531,"name":"Organic Chemistry","url":"https://www.academia.edu/Documents/in/Organic_Chemistry"},{"id":4987,"name":"Kinetics","url":"https://www.academia.edu/Documents/in/Kinetics"},{"id":12981,"name":"Enzyme Inhibitors","url":"https://www.academia.edu/Documents/in/Enzyme_Inhibitors"},{"id":69542,"name":"Computer Simulation","url":"https://www.academia.edu/Documents/in/Computer_Simulation"},{"id":147032,"name":"Naphthalimides","url":"https://www.academia.edu/Documents/in/Naphthalimides"},{"id":208178,"name":"Sirtuins","url":"https://www.academia.edu/Documents/in/Sirtuins"},{"id":213876,"name":"Docking","url":"https://www.academia.edu/Documents/in/Docking"},{"id":789996,"name":"Leishmania infantum","url":"https://www.academia.edu/Documents/in/Leishmania_infantum"},{"id":967839,"name":"Structure activity Relationship","url":"https://www.academia.edu/Documents/in/Structure_activity_Relationship"},{"id":1179557,"name":"Sirtuin","url":"https://www.academia.edu/Documents/in/Sirtuin"}],"urls":[{"id":2945786,"url":"http://doi.wiley.com/10.1002/cmdc.200900367"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143042"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143042/Antibodies_against_a_Leishmania_infantum_peroxiredoxin_as_a_possible_marker_for_diagnosis_of_visceral_leishmaniasis_and_for_monitoring_the_efficacy_of_treatment"><img alt="Research paper thumbnail of Antibodies against a Leishmania infantum peroxiredoxin as a possible marker for diagnosis of visceral leishmaniasis and for monitoring the efficacy of treatment" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143042/Antibodies_against_a_Leishmania_infantum_peroxiredoxin_as_a_possible_marker_for_diagnosis_of_visceral_leishmaniasis_and_for_monitoring_the_efficacy_of_treatment">Antibodies against a Leishmania infantum peroxiredoxin as a possible marker for diagnosis of visceral leishmaniasis and for monitoring the efficacy of treatment</a></div><div class="wp-workCard_item"><span>Immunology Letters</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Diagnosis of leishmaniasis is frequently based on serological methods, such as direct agglutinati...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Diagnosis of leishmaniasis is frequently based on serological methods, such as direct agglutination, immunofluorescence tests and ELISA assays with Leishmania total extracts, as antigen, however due to highly inconclusive results, more reliable tests are needed. In the present study, the prevalence of antibodies to a number of recombinant proteins (LmSIR2, LmS3a, LimTXNPx, LicTXNPx and LiTXN1) highly conserved among Leishmania species, were evaluated by ELISA in Leishmania infantum infected children from an endemic area of Portugal. We found that sera from children patients had antibodies against the different recombinant proteins, LicTXNPx presented the highest immuno-reactivity compared to the other and the most often recognized in the case of acute visceral leishmaniasis (VL). Moreover, in children treated with meglumine antimoniate or amphotericin B, antibodies against some of the recombinant proteins declined, whereas conventional serology using crude extracts showed little or no difference between the pre- and post-treatment values. The highest reduction was observed in the case of antibodies against the LicTXNPx protein. These results suggest that the antibodies against LicTXNPx might be a useful constituent of a defined serological test for the diagnosis and the monitoring of the therapeutic response in VL. The monitoring and follow-up in a large-scale field trials of such marker in areas where leishmaniasis is endemic will lend support to this.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143042"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143042"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143042; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143042]").text(description); $(".js-view-count[data-work-id=7143042]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143042; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143042']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143042, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=7143042]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143042,"title":"Antibodies against a Leishmania infantum peroxiredoxin as a possible marker for diagnosis of visceral leishmaniasis and for monitoring the efficacy of treatment","translated_title":"","metadata":{"abstract":"Diagnosis of leishmaniasis is frequently based on serological methods, such as direct agglutination, immunofluorescence tests and ELISA assays with Leishmania total extracts, as antigen, however due to highly inconclusive results, more reliable tests are needed. In the present study, the prevalence of antibodies to a number of recombinant proteins (LmSIR2, LmS3a, LimTXNPx, LicTXNPx and LiTXN1) highly conserved among Leishmania species, were evaluated by ELISA in Leishmania infantum infected children from an endemic area of Portugal. We found that sera from children patients had antibodies against the different recombinant proteins, LicTXNPx presented the highest immuno-reactivity compared to the other and the most often recognized in the case of acute visceral leishmaniasis (VL). Moreover, in children treated with meglumine antimoniate or amphotericin B, antibodies against some of the recombinant proteins declined, whereas conventional serology using crude extracts showed little or no difference between the pre- and post-treatment values. The highest reduction was observed in the case of antibodies against the LicTXNPx protein. These results suggest that the antibodies against LicTXNPx might be a useful constituent of a defined serological test for the diagnosis and the monitoring of the therapeutic response in VL. The monitoring and follow-up in a large-scale field trials of such marker in areas where leishmaniasis is endemic will lend support to this.","publication_date":{"day":null,"month":null,"year":2005,"errors":{}},"publication_name":"Immunology Letters"},"translated_abstract":"Diagnosis of leishmaniasis is frequently based on serological methods, such as direct agglutination, immunofluorescence tests and ELISA assays with Leishmania total extracts, as antigen, however due to highly inconclusive results, more reliable tests are needed. In the present study, the prevalence of antibodies to a number of recombinant proteins (LmSIR2, LmS3a, LimTXNPx, LicTXNPx and LiTXN1) highly conserved among Leishmania species, were evaluated by ELISA in Leishmania infantum infected children from an endemic area of Portugal. We found that sera from children patients had antibodies against the different recombinant proteins, LicTXNPx presented the highest immuno-reactivity compared to the other and the most often recognized in the case of acute visceral leishmaniasis (VL). Moreover, in children treated with meglumine antimoniate or amphotericin B, antibodies against some of the recombinant proteins declined, whereas conventional serology using crude extracts showed little or no difference between the pre- and post-treatment values. The highest reduction was observed in the case of antibodies against the LicTXNPx protein. These results suggest that the antibodies against LicTXNPx might be a useful constituent of a defined serological test for the diagnosis and the monitoring of the therapeutic response in VL. The monitoring and follow-up in a large-scale field trials of such marker in areas where leishmaniasis is endemic will lend support to this.","internal_url":"https://www.academia.edu/7143042/Antibodies_against_a_Leishmania_infantum_peroxiredoxin_as_a_possible_marker_for_diagnosis_of_visceral_leishmaniasis_and_for_monitoring_the_efficacy_of_treatment","translated_internal_url":"","created_at":"2014-05-24T01:01:49.819-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Antibodies_against_a_Leishmania_infantum_peroxiredoxin_as_a_possible_marker_for_diagnosis_of_visceral_leishmaniasis_and_for_monitoring_the_efficacy_of_treatment","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":"Diagnosis of leishmaniasis is frequently based on serological methods, such as direct agglutination, immunofluorescence tests and ELISA assays with Leishmania total extracts, as antigen, however due to highly inconclusive results, more reliable tests are needed. In the present study, the prevalence of antibodies to a number of recombinant proteins (LmSIR2, LmS3a, LimTXNPx, LicTXNPx and LiTXN1) highly conserved among Leishmania species, were evaluated by ELISA in Leishmania infantum infected children from an endemic area of Portugal. We found that sera from children patients had antibodies against the different recombinant proteins, LicTXNPx presented the highest immuno-reactivity compared to the other and the most often recognized in the case of acute visceral leishmaniasis (VL). Moreover, in children treated with meglumine antimoniate or amphotericin B, antibodies against some of the recombinant proteins declined, whereas conventional serology using crude extracts showed little or no difference between the pre- and post-treatment values. The highest reduction was observed in the case of antibodies against the LicTXNPx protein. These results suggest that the antibodies against LicTXNPx might be a useful constituent of a defined serological test for the diagnosis and the monitoring of the therapeutic response in VL. The monitoring and follow-up in a large-scale field trials of such marker in areas where leishmaniasis is endemic will lend support to this.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[],"research_interests":[{"id":1290,"name":"Immunology","url":"https://www.academia.edu/Documents/in/Immunology"},{"id":64933,"name":"Child","url":"https://www.academia.edu/Documents/in/Child"},{"id":128004,"name":"Visceral Leishmaniasis","url":"https://www.academia.edu/Documents/in/Visceral_Leishmaniasis"},{"id":320165,"name":"Field Trial","url":"https://www.academia.edu/Documents/in/Field_Trial"},{"id":568482,"name":"Biological markers","url":"https://www.academia.edu/Documents/in/Biological_markers"},{"id":758278,"name":"Large Scale","url":"https://www.academia.edu/Documents/in/Large_Scale"},{"id":789996,"name":"Leishmania infantum","url":"https://www.academia.edu/Documents/in/Leishmania_infantum"},{"id":959510,"name":"Recombinant Protein","url":"https://www.academia.edu/Documents/in/Recombinant_Protein"},{"id":1716403,"name":"immunoglobulin G","url":"https://www.academia.edu/Documents/in/immunoglobulin_G"},{"id":2211535,"name":"Peroxiredoxins","url":"https://www.academia.edu/Documents/in/Peroxiredoxins"}],"urls":[{"id":2945785,"url":"http://www.sciencedirect.com/science/article/pii/S0165247805001057"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143041"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143041/Immune_Response_Regulation_by_Leishmania_Secreted_and_Nonsecreted_Antigens"><img alt="Research paper thumbnail of Immune Response Regulation by Leishmania Secreted and Nonsecreted Antigens" class="work-thumbnail" src="https://attachments.academia-assets.com/48583923/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143041/Immune_Response_Regulation_by_Leishmania_Secreted_and_Nonsecreted_Antigens">Immune Response Regulation by Leishmania Secreted and Nonsecreted Antigens</a></div><div class="wp-workCard_item"><span>Journal of Biomedicine and Biotechnology</span><span>, 2007</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Leishmania infection consists in two sequential events, the host cell colonization followed by th...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Leishmania infection consists in two sequential events, the host cell colonization followed by the proliferation/dissemination of the parasite. In this review, we discuss the importance of two distinct sets of molecules, the secreted and/or surface and the nonsecreted antigens. The importance of the immune response against secreted and surface antigens is noted in the establishment of the infection and we dissect the contribution of the nonsecreted antigens in the immunopathology associated with leishmaniasis, showing the importance of these panantigens during the course of the infection. As a further example of proteins belonging to these two different groups, we include several laboratorial observations on Leishmania Sir2 and LicTXNPx as excreted/secreted proteins and LmS3arp and LimTXNPx as nonsecreted/panantigens. The role of these two groups of antigens in the immune response observed during the infection is discussed.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="6491f53c5b831867ad14bab3bcdc3e23" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583923,"asset_id":7143041,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583923/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143041"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143041"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143041; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143041]").text(description); $(".js-view-count[data-work-id=7143041]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143041; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143041']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143041, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "6491f53c5b831867ad14bab3bcdc3e23" } } $('.js-work-strip[data-work-id=7143041]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143041,"title":"Immune Response Regulation by Leishmania Secreted and Nonsecreted Antigens","translated_title":"","metadata":{"grobid_abstract":"Leishmania infection consists in two sequential events, the host cell colonization followed by the proliferation/dissemination of the parasite. In this review, we discuss the importance of two distinct sets of molecules, the secreted and/or surface and the nonsecreted antigens. The importance of the immune response against secreted and surface antigens is noted in the establishment of the infection and we dissect the contribution of the nonsecreted antigens in the immunopathology associated with leishmaniasis, showing the importance of these panantigens during the course of the infection. As a further example of proteins belonging to these two different groups, we include several laboratorial observations on Leishmania Sir2 and LicTXNPx as excreted/secreted proteins and LmS3arp and LimTXNPx as nonsecreted/panantigens. The role of these two groups of antigens in the immune response observed during the infection is discussed.","publication_date":{"day":null,"month":null,"year":2007,"errors":{}},"publication_name":"Journal of Biomedicine and Biotechnology","grobid_abstract_attachment_id":48583923},"translated_abstract":null,"internal_url":"https://www.academia.edu/7143041/Immune_Response_Regulation_by_Leishmania_Secreted_and_Nonsecreted_Antigens","translated_internal_url":"","created_at":"2014-05-24T01:01:49.529-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583923,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583923/thumbnails/1.jpg","file_name":"Immune_response_regulation_by_leishmania20160905-28746-1zzr7w.pdf","download_url":"https://www.academia.edu/attachments/48583923/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Immune_Response_Regulation_by_Leishmania.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583923/Immune_response_regulation_by_leishmania20160905-28746-1zzr7w-libre.pdf?1473073947=\u0026response-content-disposition=attachment%3B+filename%3DImmune_Response_Regulation_by_Leishmania.pdf\u0026Expires=1736775918\u0026Signature=fba9JdVXMf9htOejxMQ~54YQ66VJpaiGyNVxjxuDwShnSS8ll2tQXcHz1QIEiD9oM5SqN5UIXYuURbYTnuNtVJapMtYoDOxu6HGWrIWvlz1UIj89E3YAqEMZyuOhgSs0S7Ox-2yGkaQbao9rfZ1vNrd9TYvpvjdag~siil~OxselhDJPMB3zf8fQ13BMMen5-gpOZQVoqKR-2JOpMNBlKqd~i05kSr8nwJV74TSIS0fvUR8ZU6NsXgUp~6qglt8O~sQhBawe2NB-9JF3duhX1i4~Rkfl1oBFPEMGHdCAQ4QWfHZ2jVoy9HMNvU-rxCa~wHjGExzYNj0Zzs0w-yvdrg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Immune_Response_Regulation_by_Leishmania_Secreted_and_Nonsecreted_Antigens","translated_slug":"","page_count":10,"language":"en","content_type":"Work","summary":"Leishmania infection consists in two sequential events, the host cell colonization followed by the proliferation/dissemination of the parasite. In this review, we discuss the importance of two distinct sets of molecules, the secreted and/or surface and the nonsecreted antigens. The importance of the immune response against secreted and surface antigens is noted in the establishment of the infection and we dissect the contribution of the nonsecreted antigens in the immunopathology associated with leishmaniasis, showing the importance of these panantigens during the course of the infection. As a further example of proteins belonging to these two different groups, we include several laboratorial observations on Leishmania Sir2 and LicTXNPx as excreted/secreted proteins and LmS3arp and LimTXNPx as nonsecreted/panantigens. The role of these two groups of antigens in the immune response observed during the infection is discussed.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583923,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583923/thumbnails/1.jpg","file_name":"Immune_response_regulation_by_leishmania20160905-28746-1zzr7w.pdf","download_url":"https://www.academia.edu/attachments/48583923/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Immune_Response_Regulation_by_Leishmania.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583923/Immune_response_regulation_by_leishmania20160905-28746-1zzr7w-libre.pdf?1473073947=\u0026response-content-disposition=attachment%3B+filename%3DImmune_Response_Regulation_by_Leishmania.pdf\u0026Expires=1736775918\u0026Signature=fba9JdVXMf9htOejxMQ~54YQ66VJpaiGyNVxjxuDwShnSS8ll2tQXcHz1QIEiD9oM5SqN5UIXYuURbYTnuNtVJapMtYoDOxu6HGWrIWvlz1UIj89E3YAqEMZyuOhgSs0S7Ox-2yGkaQbao9rfZ1vNrd9TYvpvjdag~siil~OxselhDJPMB3zf8fQ13BMMen5-gpOZQVoqKR-2JOpMNBlKqd~i05kSr8nwJV74TSIS0fvUR8ZU6NsXgUp~6qglt8O~sQhBawe2NB-9JF3duhX1i4~Rkfl1oBFPEMGHdCAQ4QWfHZ2jVoy9HMNvU-rxCa~wHjGExzYNj0Zzs0w-yvdrg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":923,"name":"Technology","url":"https://www.academia.edu/Documents/in/Technology"},{"id":1066,"name":"Biomedicine","url":"https://www.academia.edu/Documents/in/Biomedicine"},{"id":2702,"name":"Immune response","url":"https://www.academia.edu/Documents/in/Immune_response"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":222543,"name":"Biomed","url":"https://www.academia.edu/Documents/in/Biomed"}],"urls":[{"id":2945784,"url":"http://www.hindawi.com/journals/jbb/2007/085154.pdf"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143040"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143040/Activation_of_Phosphatidylinositol_3Kinase_Akt_and_Impairment_of_Nuclear_Factor_%CE%BAB"><img alt="Research paper thumbnail of Activation of Phosphatidylinositol 3Kinase/Akt and Impairment of Nuclear Factor-κB" class="work-thumbnail" src="https://attachments.academia-assets.com/48583913/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143040/Activation_of_Phosphatidylinositol_3Kinase_Akt_and_Impairment_of_Nuclear_Factor_%CE%BAB">Activation of Phosphatidylinositol 3Kinase/Akt and Impairment of Nuclear Factor-κB</a></div><div class="wp-workCard_item"><span>American Journal of Pathology</span><span>, 2010</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Supported by Fundaç ã o para a Ciê ncia e a Tecnologia (FCT) and Fundo Europeu de Desenvolvimento...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Supported by Fundaç ã o para a Ciê ncia e a Tecnologia (FCT) and Fundo Europeu de Desenvolvimento Regional (FEDER) Ciê ncia Bone marrow-dendritic cells (BMDCs) were derived as described previously. In brief, bone marrow from femurs and tibiae of 10-to 12-week-old BALB/c mice were flushed with RPMI 1640, using syringes and 25-gauge needles. The tissue was resuspended, and BMDCs were obtained by seeding 5 ϫ 10 6 bone marrow cells in 25 ml of RPMIc supplemented with 50 mol/L 2-mercaptoethanol (Sigma Chemical Co.) and 200 U/ml of granulocyte macrophage-colony-stimulating factor (GM-CSF) (PeproTech, Rocky Hill, NJ) (DC medium).</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="65762f2053d856e3ce9edf44d951b02e" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583913,"asset_id":7143040,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583913/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143040"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143040"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143040; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143040]").text(description); $(".js-view-count[data-work-id=7143040]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143040; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143040']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143040, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "65762f2053d856e3ce9edf44d951b02e" } } $('.js-work-strip[data-work-id=7143040]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143040,"title":"Activation of Phosphatidylinositol 3Kinase/Akt and Impairment of Nuclear Factor-κB","translated_title":"","metadata":{"grobid_abstract":"Supported by Fundaç ã o para a Ciê ncia e a Tecnologia (FCT) and Fundo Europeu de Desenvolvimento Regional (FEDER) Ciê ncia Bone marrow-dendritic cells (BMDCs) were derived as described previously. In brief, bone marrow from femurs and tibiae of 10-to 12-week-old BALB/c mice were flushed with RPMI 1640, using syringes and 25-gauge needles. The tissue was resuspended, and BMDCs were obtained by seeding 5 ϫ 10 6 bone marrow cells in 25 ml of RPMIc supplemented with 50 mol/L 2-mercaptoethanol (Sigma Chemical Co.) and 200 U/ml of granulocyte macrophage-colony-stimulating factor (GM-CSF) (PeproTech, Rocky Hill, NJ) (DC medium).","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"American Journal of Pathology","grobid_abstract_attachment_id":48583913},"translated_abstract":null,"internal_url":"https://www.academia.edu/7143040/Activation_of_Phosphatidylinositol_3Kinase_Akt_and_Impairment_of_Nuclear_Factor_%CE%BAB","translated_internal_url":"","created_at":"2014-05-24T01:01:49.188-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583913,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583913/thumbnails/1.jpg","file_name":"Activation_of_phosphatidylinositol_3-kin20160905-16660-9jtm19.pdf","download_url":"https://www.academia.edu/attachments/48583913/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Activation_of_Phosphatidylinositol_3Kina.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583913/Activation_of_phosphatidylinositol_3-kin20160905-16660-9jtm19-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DActivation_of_Phosphatidylinositol_3Kina.pdf\u0026Expires=1736775918\u0026Signature=PtmrLBqZHb7AC7IeRJhFH6QKVbn4kEZzgUnEMtSAMduP4mUaCzWK43CpvDVTAie4bmmnuf2hKBFUHTNhDFq1hiakZ-6l5cBgscPTrkT6bV8O-~gpK~joDW0flVKSGew73nI~DCH9HEPJ2moQ9V8ASBf1plbjNeVKEmsBsByuIjFkhjSYvbWCK8RxqshXDdThkxsu4sENq0Ay7wTwjy4gSkB9DTfpNqzDeY-c9W-WorutEpkKTacrWeIhaOPlS~QUWdKVCenFiOc11CMnvYpBMIyAPK1wMWSZSAYQmrJ3fXjwSxD6BbTtyC8J4gAIU8bBbRUX1OWaX1qv49vkExz4QA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Activation_of_Phosphatidylinositol_3Kinase_Akt_and_Impairment_of_Nuclear_Factor_κB","translated_slug":"","page_count":14,"language":"en","content_type":"Work","summary":"Supported by Fundaç ã o para a Ciê ncia e a Tecnologia (FCT) and Fundo Europeu de Desenvolvimento Regional (FEDER) Ciê ncia Bone marrow-dendritic cells (BMDCs) were derived as described previously. In brief, bone marrow from femurs and tibiae of 10-to 12-week-old BALB/c mice were flushed with RPMI 1640, using syringes and 25-gauge needles. 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nanoparticles" class="work-thumbnail" src="https://attachments.academia-assets.com/48583940/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143039/Immune_response_by_nasal_delivery_of_hepatitis_B_surface_antigen_and_codelivery_of_a_CpG_ODN_in_alginate_coated_chitosan_nanoparticles">Immune response by nasal delivery of hepatitis B surface antigen and codelivery of a CpG ODN in alginate coated chitosan nanoparticles</a></div><div class="wp-workCard_item"><span>European Journal of Pharmaceutics and Biopharmaceutics</span><span>, 2008</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Alginate coated chitosan nanoparticles were previously developed with the aim of protecting the a...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Alginate coated chitosan nanoparticles were previously developed with the aim of protecting the antigen, adsorbed on the surface of those chitosan nanoparticles, from enzymatic degradation at mucosal surfaces. In this work, this new delivery system was loaded with the recombinant hepatitis B surface antigen (HBsAg) and applied to mice by the intranasal route. Adjuvant effect of the delivery system was studied by measuring anti-HBsAg IgG in serum, anti-HBsAg sIgA in faeces extracts or nasal and vaginal secretions and interferon-c production in supernatants of the spleen cells. The mice were primed with 10 lg of the vaccine associated or not with nanoparticles and associated or not with 10 lg CpG oligodeoxynucleotide (ODN) followed by two sequential boosts at three week intervals. The association of HBsAg with the alginate coated chitosan nanoparticles, administered intranasally to the mice, gave rise to the humoral mucosal immune response. Humoral systemic immune response was not induced by the HBsAg loaded nanoparticles alone. The generation of Th1-biased antigen-specific systemic antibodies, however, was observed when HBsAg loaded nanoparticles were applied together with a second adjuvant, the immunopotentiator, CpG ODN. Moreover, all intranasally vaccinated groups showed higher interferon-c production when compared to naïve mice.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="f6ffc4d4ed4335092b349bd3b07b9333" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583940,"asset_id":7143039,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583940/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143039"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143039"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143039; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143039]").text(description); $(".js-view-count[data-work-id=7143039]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143039; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143039']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143039, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "f6ffc4d4ed4335092b349bd3b07b9333" } } $('.js-work-strip[data-work-id=7143039]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143039,"title":"Immune response by nasal delivery of hepatitis B surface antigen and codelivery of a CpG ODN in alginate coated chitosan nanoparticles","translated_title":"","metadata":{"ai_title_tag":"Nasal Delivery of HBsAg via Chitosan Nanoparticles and CpG ODN","grobid_abstract":"Alginate coated chitosan nanoparticles were previously developed with the aim of protecting the antigen, adsorbed on the surface of those chitosan nanoparticles, from enzymatic degradation at mucosal surfaces. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143038"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143038/Structure_Function_Analysis_of_Leishmania_Sirtuin_An_Ensemble_of_In_Silico_and_Biochemical_Studies"><img alt="Research paper thumbnail of Structure Function Analysis of Leishmania Sirtuin: An Ensemble of In Silico and Biochemical Studies" class="work-thumbnail" src="https://attachments.academia-assets.com/48583889/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143038/Structure_Function_Analysis_of_Leishmania_Sirtuin_An_Ensemble_of_In_Silico_and_Biochemical_Studies">Structure Function Analysis of Leishmania Sirtuin: An Ensemble of In Silico and Biochemical Studies</a></div><div class="wp-workCard_item"><span>Chemical Biology & Drug Design</span><span>, 2008</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Novel anti-leishmanial target LmSir2 has few subtle but prudent structural differences in ligand ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Novel anti-leishmanial target LmSir2 has few subtle but prudent structural differences in ligand binding and catalytic domain as compared to its human counterpart. In silico screening and validation followed by in vitro deacetylation and cell killing assays described herein give a proof of concept for development of strategies exploiting such minor differences for screening libraries of small molecules to identify selective inhibitors.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="8a75798a0c3d95fd671fdd321f19f7f7" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583889,"asset_id":7143038,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583889/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143038"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143038"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143038; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143038]").text(description); $(".js-view-count[data-work-id=7143038]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143038; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143038']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143038, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "8a75798a0c3d95fd671fdd321f19f7f7" } } $('.js-work-strip[data-work-id=7143038]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143038,"title":"Structure Function Analysis of Leishmania Sirtuin: An Ensemble of In Silico and Biochemical Studies","translated_title":"","metadata":{"abstract":"Novel anti-leishmanial target LmSir2 has few subtle but prudent structural differences in ligand binding and catalytic domain as compared to its human counterpart. 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DPH fluorescence quenching studies revealed that the NSAIDs studied were able to efficiently quench the probe located in membrane hydrocarbon region. Fluorescence anisotropy measurements were also made to investigate the effects on membrane fluidity resulting from the interaction between the drugs and membrane systems. All the anti-inflammatory drugs studied show an increase in the membrane fluidity in a concentration dependent manner. Results obtained provide an insight into NSAIDs capacity to be inserted in lipid bilayers and alter the lipid dynamics. The induced changes in lipid dynamics may modulate the activity of inflammatory enzymes or may be related with deleterious topical action of NSAIDs on gastric phospholipid fluidity. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 3195–3206, 2008</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143037"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143037"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143037; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143037]").text(description); $(".js-view-count[data-work-id=7143037]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143037; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143037']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143037, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=7143037]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143037,"title":"Effect of nonsteroidal anti‐inflammatory drugs on the cellular membrane fluidity","translated_title":"","metadata":{"abstract":"In this work, fluorescence measurements were performed using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) to evaluate the effects of the interaction of nonsteroidal anti-inflammatory drugs—NSAIDs (meloxicam, lornoxicam, and nimesulide) with several membrane systems (liposomes with and without cholesterol, mouse splenocytes, mouse macrophages cell line—J774, human leukemia monocyte cell line—THP-1, and human granulocytes and mononuclear cells). DPH fluorescence quenching studies revealed that the NSAIDs studied were able to efficiently quench the probe located in membrane hydrocarbon region. Fluorescence anisotropy measurements were also made to investigate the effects on membrane fluidity resulting from the interaction between the drugs and membrane systems. All the anti-inflammatory drugs studied show an increase in the membrane fluidity in a concentration dependent manner. Results obtained provide an insight into NSAIDs capacity to be inserted in lipid bilayers and alter the lipid dynamics. The induced changes in lipid dynamics may modulate the activity of inflammatory enzymes or may be related with deleterious topical action of NSAIDs on gastric phospholipid fluidity. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 3195–3206, 2008","publication_date":{"day":null,"month":null,"year":2008,"errors":{}},"publication_name":"Journal of Pharmaceutical Sciences"},"translated_abstract":"In this work, fluorescence measurements were performed using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) to evaluate the effects of the interaction of nonsteroidal anti-inflammatory drugs—NSAIDs (meloxicam, lornoxicam, and nimesulide) with several membrane systems (liposomes with and without cholesterol, mouse splenocytes, mouse macrophages cell line—J774, human leukemia monocyte cell line—THP-1, and human granulocytes and mononuclear cells). DPH fluorescence quenching studies revealed that the NSAIDs studied were able to efficiently quench the probe located in membrane hydrocarbon region. Fluorescence anisotropy measurements were also made to investigate the effects on membrane fluidity resulting from the interaction between the drugs and membrane systems. All the anti-inflammatory drugs studied show an increase in the membrane fluidity in a concentration dependent manner. Results obtained provide an insight into NSAIDs capacity to be inserted in lipid bilayers and alter the lipid dynamics. The induced changes in lipid dynamics may modulate the activity of inflammatory enzymes or may be related with deleterious topical action of NSAIDs on gastric phospholipid fluidity. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 3195–3206, 2008","internal_url":"https://www.academia.edu/7143037/Effect_of_nonsteroidal_anti_inflammatory_drugs_on_the_cellular_membrane_fluidity","translated_internal_url":"","created_at":"2014-05-24T01:01:48.522-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Effect_of_nonsteroidal_anti_inflammatory_drugs_on_the_cellular_membrane_fluidity","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":"In this work, fluorescence measurements were performed using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) to evaluate the effects of the interaction of nonsteroidal anti-inflammatory drugs—NSAIDs (meloxicam, lornoxicam, and nimesulide) with several membrane systems (liposomes with and without cholesterol, mouse splenocytes, mouse macrophages cell line—J774, human leukemia monocyte cell line—THP-1, and human granulocytes and mononuclear cells). DPH fluorescence quenching studies revealed that the NSAIDs studied were able to efficiently quench the probe located in membrane hydrocarbon region. Fluorescence anisotropy measurements were also made to investigate the effects on membrane fluidity resulting from the interaction between the drugs and membrane systems. All the anti-inflammatory drugs studied show an increase in the membrane fluidity in a concentration dependent manner. Results obtained provide an insight into NSAIDs capacity to be inserted in lipid bilayers and alter the lipid dynamics. The induced changes in lipid dynamics may modulate the activity of inflammatory enzymes or may be related with deleterious topical action of NSAIDs on gastric phospholipid fluidity. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 3195–3206, 2008","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[],"research_interests":[{"id":89956,"name":"Pharmaceutical Sciences","url":"https://www.academia.edu/Documents/in/Pharmaceutical_Sciences"}],"urls":[{"id":2945780,"url":"http://doi.wiley.com/10.1002/jps.21218"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143036"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143036/Antibodies_against_a_peroxiredoxin_as_a_possible_marker_for_diagnosis_of_visceral_leishmaniasis_and_for_monitoring_the_efficacy_of_treatment"><img alt="Research paper thumbnail of Antibodies against a peroxiredoxin as a possible marker for diagnosis of visceral leishmaniasis and for monitoring the efficacy of treatment" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143036/Antibodies_against_a_peroxiredoxin_as_a_possible_marker_for_diagnosis_of_visceral_leishmaniasis_and_for_monitoring_the_efficacy_of_treatment">Antibodies against a peroxiredoxin as a possible marker for diagnosis of visceral leishmaniasis and for monitoring the efficacy of treatment</a></div><div class="wp-workCard_item"><span>Immunology Letters</span><span>, 2005</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143036"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143036"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143036; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143036]").text(description); $(".js-view-count[data-work-id=7143036]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143036; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143036']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143036, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143035"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143035/Targeted_disruption_of_cytosolic_SIR2_deacetylase_discloses_its_essential_role_in_Leishmania_survival_and_proliferation"><img alt="Research paper thumbnail of Targeted disruption of cytosolic SIR2 deacetylase discloses its essential role in Leishmania survival and proliferation" class="work-thumbnail" src="https://attachments.academia-assets.com/48583953/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143035/Targeted_disruption_of_cytosolic_SIR2_deacetylase_discloses_its_essential_role_in_Leishmania_survival_and_proliferation">Targeted disruption of cytosolic SIR2 deacetylase discloses its essential role in Leishmania survival and proliferation</a></div><div class="wp-workCard_item"><span>Gene</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Proteins of the SIR2 family are characterized by a conserved catalytic domain that exerts unique ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Proteins of the SIR2 family are characterized by a conserved catalytic domain that exerts unique NAD-dependent deacetylase activity on histone and various other cellular substrates. Functional analyses of such proteins have been carried out in a number of prokaryotes and eukaryotes organisms but until now, none have described an essential function for any SIR2 genes. Here using genetic approach, we report that a cytosolic SIR2 homolog in Leishmania is determinant to parasite survival. L. infantum promastigote tolerates deletion of one wild-type LiSIR2 allele (LiSIR2+/−) but achievement of null chromosomal mutants (LiSIR2−/−) requires episomal rescue. Accordingly, plasmid cure shows that these parasites maintain episome even in absence of drug pressure. Though single LiSIR2 gene disruption (LiSIR2+/−) does not affect the growth of parasite in the promastigote form, axenic amastigotes display a marked reduction in their capacity to multiply in vitro inside macrophages and in vivo in Balb/c mice. Taken together these data support a stage specific requirement and/or activity of the Leishmania cytosolic SIR2 protein and reveal an unrelated essential function for the life cycle of this unicellular pathogenic organism. The lack of an effective vaccine against leishmaniasis, and the need for alternative drug treatments, makes LiSIR2 protein a new attractive therapeutic target. Gene 363 (2005) 85 -96 <a href="http://www.elsevier.com/locate/gene" rel="nofollow">www.elsevier.com/locate/gene</a> Abbreviations: LiSIR2, Leishmania infantum Silent Information Regulatory gene homologue; pXG-BSDLiSIR2 plasmid, plamid which confers resistance to Blasticidin and carrying the LiSIR2 gene; PFGE, Pulse field gel electrophoresis; NAD, nicotinamide-adenine dinucleotide; HDAC, histone deacetylase; WT, wild type parasite clone; neo and hyg, the neomycin phosphotransferase and the hygromicin phosphotransferase cassettes, respectively; ORF, open reading frame. ⁎ Corresponding author. Tel./</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="52e5f8a54450b83393277614402949af" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583953,"asset_id":7143035,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583953/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143035"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143035"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143035; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143035]").text(description); $(".js-view-count[data-work-id=7143035]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143035; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143035']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143035, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "52e5f8a54450b83393277614402949af" } } $('.js-work-strip[data-work-id=7143035]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143035,"title":"Targeted disruption of cytosolic SIR2 deacetylase discloses its essential role in Leishmania survival and proliferation","translated_title":"","metadata":{"ai_title_tag":"Role of Cytosolic SIR2 in Leishmania Survival and Proliferation","grobid_abstract":"Proteins of the SIR2 family are characterized by a conserved catalytic domain that exerts unique NAD-dependent deacetylase activity on histone and various other cellular substrates. Functional analyses of such proteins have been carried out in a number of prokaryotes and eukaryotes organisms but until now, none have described an essential function for any SIR2 genes. Here using genetic approach, we report that a cytosolic SIR2 homolog in Leishmania is determinant to parasite survival. L. infantum promastigote tolerates deletion of one wild-type LiSIR2 allele (LiSIR2+/−) but achievement of null chromosomal mutants (LiSIR2−/−) requires episomal rescue. Accordingly, plasmid cure shows that these parasites maintain episome even in absence of drug pressure. Though single LiSIR2 gene disruption (LiSIR2+/−) does not affect the growth of parasite in the promastigote form, axenic amastigotes display a marked reduction in their capacity to multiply in vitro inside macrophages and in vivo in Balb/c mice. Taken together these data support a stage specific requirement and/or activity of the Leishmania cytosolic SIR2 protein and reveal an unrelated essential function for the life cycle of this unicellular pathogenic organism. The lack of an effective vaccine against leishmaniasis, and the need for alternative drug treatments, makes LiSIR2 protein a new attractive therapeutic target. Gene 363 (2005) 85 -96 www.elsevier.com/locate/gene Abbreviations: LiSIR2, Leishmania infantum Silent Information Regulatory gene homologue; pXG-BSDLiSIR2 plasmid, plamid which confers resistance to Blasticidin and carrying the LiSIR2 gene; PFGE, Pulse field gel electrophoresis; NAD, nicotinamide-adenine dinucleotide; HDAC, histone deacetylase; WT, wild type parasite clone; neo and hyg, the neomycin phosphotransferase and the hygromicin phosphotransferase cassettes, respectively; ORF, open reading frame. ⁎ Corresponding author. Tel./","publication_date":{"day":null,"month":null,"year":2005,"errors":{}},"publication_name":"Gene","grobid_abstract_attachment_id":48583953},"translated_abstract":null,"internal_url":"https://www.academia.edu/7143035/Targeted_disruption_of_cytosolic_SIR2_deacetylase_discloses_its_essential_role_in_Leishmania_survival_and_proliferation","translated_internal_url":"","created_at":"2014-05-24T01:01:48.034-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583953,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583953/thumbnails/1.jpg","file_name":"Targeted_disruption_of_cytosolic_SIR2_de20160905-30903-zdb7ox.pdf","download_url":"https://www.academia.edu/attachments/48583953/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Targeted_disruption_of_cytosolic_SIR2_de.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583953/Targeted_disruption_of_cytosolic_SIR2_de20160905-30903-zdb7ox-libre.pdf?1473073944=\u0026response-content-disposition=attachment%3B+filename%3DTargeted_disruption_of_cytosolic_SIR2_de.pdf\u0026Expires=1736775918\u0026Signature=Dr2hd8SBclJBzVcv8RRUivCqOvg8CMKBxsZgACbUBQeRpqKdFJ8XW64tVuXdykNYEO-QR8~pBWbt3MJKdSm3xoN24BwseQfwihgCLGuC3VBwZBWCpq2O6Avig8vtp1BJX11oUDv-OUdjwbe-JADspL3a4XBNHvQShz7kJQgcWcFFtA-fb-7yg30y5HOmQr07AviGw3b1mE4A9TFRE6qHikPBRcwDe9h0EvYbZ0OIFbETowziBbkRHrWqCe4rQKyPvlY3K0X6moab~fgXU43D8ThzX5efR-2TDhHJeXw8oSjALHUfVnXvGpA0AVrDVqhTymH9uwAr9e~C6~5hljAyrg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Targeted_disruption_of_cytosolic_SIR2_deacetylase_discloses_its_essential_role_in_Leishmania_survival_and_proliferation","translated_slug":"","page_count":12,"language":"en","content_type":"Work","summary":"Proteins of the SIR2 family are characterized by a conserved catalytic domain that exerts unique NAD-dependent deacetylase activity on histone and various other cellular substrates. Functional analyses of such proteins have been carried out in a number of prokaryotes and eukaryotes organisms but until now, none have described an essential function for any SIR2 genes. Here using genetic approach, we report that a cytosolic SIR2 homolog in Leishmania is determinant to parasite survival. L. infantum promastigote tolerates deletion of one wild-type LiSIR2 allele (LiSIR2+/−) but achievement of null chromosomal mutants (LiSIR2−/−) requires episomal rescue. Accordingly, plasmid cure shows that these parasites maintain episome even in absence of drug pressure. Though single LiSIR2 gene disruption (LiSIR2+/−) does not affect the growth of parasite in the promastigote form, axenic amastigotes display a marked reduction in their capacity to multiply in vitro inside macrophages and in vivo in Balb/c mice. Taken together these data support a stage specific requirement and/or activity of the Leishmania cytosolic SIR2 protein and reveal an unrelated essential function for the life cycle of this unicellular pathogenic organism. The lack of an effective vaccine against leishmaniasis, and the need for alternative drug treatments, makes LiSIR2 protein a new attractive therapeutic target. Gene 363 (2005) 85 -96 www.elsevier.com/locate/gene Abbreviations: LiSIR2, Leishmania infantum Silent Information Regulatory gene homologue; pXG-BSDLiSIR2 plasmid, plamid which confers resistance to Blasticidin and carrying the LiSIR2 gene; PFGE, Pulse field gel electrophoresis; NAD, nicotinamide-adenine dinucleotide; HDAC, histone deacetylase; WT, wild type parasite clone; neo and hyg, the neomycin phosphotransferase and the hygromicin phosphotransferase cassettes, respectively; ORF, open reading frame. ⁎ Corresponding author. 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In the case of protozoan species that are causative agents of important human diseases such as Leishmaniasis, an exogenous supply of polyamines supports parasite proliferation. In the present study, we have investigated the effect of three polyamine derivatives, (namely bisnaphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd) and spermine (BNIPSpm)), on the proliferative stages of Leishmania infantum, the causative agent of visceral leishmaniasis in the Mediterranean basin. A significant reduction of promastigotes and axenic amastigotes growth was observed in the presence of increasing concentrations of the drugs, although the mechanisms leading to the parasite growth arrest seems to be different. Indeed, by using a number of biochemical approaches to analyse the alterations that occurred during early stages of parasite-drug interaction (i.e. membrane phosphatidylserine exposure measured by annexin V binding, DNA fragmentation, deoxynucleotidyltranferase-mediated dUTP end labelin (TUNEL), mitochondrial transmembrane potential loss), we showed that the drugs had the capacity to induce the death of promastigotes by a mechanism that shares many features with metazoan apoptosis. Surprisingly, the amastigotes did not behave in a similar way to promastigotes. The drug inhibitory effect on amastigotes growth and the absence of propidium iodide labelling may suggest that the compounds are acting as cytostatic substances. Although, the mechanisms of action of these compounds have yet to be elucidated, the above data show for the first time that polyamine derivatives may act differentially on the Leishmania parasite stages. Further chemical modifications are needed to make the polyamine derivatives as well as other analogues able to target the amastigote stage of the parasite. q</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="b7904a893a506074592e8bd5afd0a4ac" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583932,"asset_id":7143034,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583932/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143034"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143034"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143034; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143034]").text(description); $(".js-view-count[data-work-id=7143034]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143034; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143034']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143034, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "b7904a893a506074592e8bd5afd0a4ac" } } $('.js-work-strip[data-work-id=7143034]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143034,"title":"Differential effects of polyamine derivative compounds against promastigotes and axenic amastigotes","translated_title":"","metadata":{"grobid_abstract":"The natural polyamines are ubiquitous polycationic compounds that play important biological functions in cell growth and differentiation. 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Indeed, by using a number of biochemical approaches to analyse the alterations that occurred during early stages of parasite-drug interaction (i.e. membrane phosphatidylserine exposure measured by annexin V binding, DNA fragmentation, deoxynucleotidyltranferase-mediated dUTP end labelin (TUNEL), mitochondrial transmembrane potential loss), we showed that the drugs had the capacity to induce the death of promastigotes by a mechanism that shares many features with metazoan apoptosis. Surprisingly, the amastigotes did not behave in a similar way to promastigotes. The drug inhibitory effect on amastigotes growth and the absence of propidium iodide labelling may suggest that the compounds are acting as cytostatic substances. Although, the mechanisms of action of these compounds have yet to be elucidated, the above data show for the first time that polyamine derivatives may act differentially on the Leishmania parasite stages. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143033"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143033/Evaluation_of_the_immune_response_following_a_short_oral_vaccination_schedule_with_hepatitis_B_antigen_encapsulated_into_alginate_coated_chitosan_nanoparticles"><img alt="Research paper thumbnail of Evaluation of the immune response following a short oral vaccination schedule with hepatitis B antigen encapsulated into alginate-coated chitosan nanoparticles" class="work-thumbnail" src="https://attachments.academia-assets.com/48583981/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143033/Evaluation_of_the_immune_response_following_a_short_oral_vaccination_schedule_with_hepatitis_B_antigen_encapsulated_into_alginate_coated_chitosan_nanoparticles">Evaluation of the immune response following a short oral vaccination schedule with hepatitis B antigen encapsulated into alginate-coated chitosan nanoparticles</a></div><div class="wp-workCard_item"><span>European Journal of Pharmaceutical Sciences</span><span>, 2007</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Hepatitis B surface antigen CpG oligodeoxynucleotide Alginate-coated chitosan nanoparticles Vacci...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Hepatitis B surface antigen CpG oligodeoxynucleotide Alginate-coated chitosan nanoparticles Vaccines a b s t r a c t The purpose of this work was to assess the ability of recombinant hepatitis B vaccine, encapsulated in alginate-coated chitosan nanoparticles, to induce local and systemic immune responses following oral vaccination. The antigen was administered either alone or in combination with the immunopotentiator, synthetic oligodeoxynucleotide containing immunostimulatory CpG motif (CpG ODN) as adjuvant, and associated or not with the alginate-coated chitosan nanoparticles. After two immunizations the group I (HBsAg associated with nanoparticles) and the group VI (HBsAg and CpG, both associated with nanoparticles) showed enhanced immune responses. Both groups showed significant higher values of the CD69 expression in CD4+ and CD8+ T-lymphocytes and lower values of this marker in B lymphocytes. Moreover, a strongest proliferative response of the splenocytes, ex vivo stimulated with concanavalin A, was observed in the same groups. Although with a presence of non-responder mice within the groups, only mice of the groups I and VI elicited the generation of anti-HBsAg antibodies detected in serum (IgG) and in the intestinal washings (sIgA). The results demonstrated that coated chitosan nanoparticles might have potential for being used as a deliver system for oral vaccination with the recombinant hepatitis B surface antigen. (O. Borges).</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="ca2d7c7d0bc091339b4e357b57a4a9c2" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583981,"asset_id":7143033,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583981/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143033"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143033"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143033; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143033]").text(description); $(".js-view-count[data-work-id=7143033]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143033; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143033']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143033, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "ca2d7c7d0bc091339b4e357b57a4a9c2" } } $('.js-work-strip[data-work-id=7143033]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143033,"title":"Evaluation of the immune response following a short oral vaccination schedule with hepatitis B antigen encapsulated into alginate-coated chitosan nanoparticles","translated_title":"","metadata":{"grobid_abstract":"Hepatitis B surface antigen CpG oligodeoxynucleotide Alginate-coated chitosan nanoparticles Vaccines a b s t r a c t The purpose of this work was to assess the ability of recombinant hepatitis B vaccine, encapsulated in alginate-coated chitosan nanoparticles, to induce local and systemic immune responses following oral vaccination. The antigen was administered either alone or in combination with the immunopotentiator, synthetic oligodeoxynucleotide containing immunostimulatory CpG motif (CpG ODN) as adjuvant, and associated or not with the alginate-coated chitosan nanoparticles. After two immunizations the group I (HBsAg associated with nanoparticles) and the group VI (HBsAg and CpG, both associated with nanoparticles) showed enhanced immune responses. Both groups showed significant higher values of the CD69 expression in CD4+ and CD8+ T-lymphocytes and lower values of this marker in B lymphocytes. Moreover, a strongest proliferative response of the splenocytes, ex vivo stimulated with concanavalin A, was observed in the same groups. Although with a presence of non-responder mice within the groups, only mice of the groups I and VI elicited the generation of anti-HBsAg antibodies detected in serum (IgG) and in the intestinal washings (sIgA). 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The antigen was administered either alone or in combination with the immunopotentiator, synthetic oligodeoxynucleotide containing immunostimulatory CpG motif (CpG ODN) as adjuvant, and associated or not with the alginate-coated chitosan nanoparticles. After two immunizations the group I (HBsAg associated with nanoparticles) and the group VI (HBsAg and CpG, both associated with nanoparticles) showed enhanced immune responses. Both groups showed significant higher values of the CD69 expression in CD4+ and CD8+ T-lymphocytes and lower values of this marker in B lymphocytes. Moreover, a strongest proliferative response of the splenocytes, ex vivo stimulated with concanavalin A, was observed in the same groups. Although with a presence of non-responder mice within the groups, only mice of the groups I and VI elicited the generation of anti-HBsAg antibodies detected in serum (IgG) and in the intestinal washings (sIgA). 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Borges).","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583981,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583981/thumbnails/1.jpg","file_name":"Evaluation_of_the_immune_response_follow20160905-16653-1dn9udf.pdf","download_url":"https://www.academia.edu/attachments/48583981/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Evaluation_of_the_immune_response_follow.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583981/Evaluation_of_the_immune_response_follow20160905-16653-1dn9udf-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DEvaluation_of_the_immune_response_follow.pdf\u0026Expires=1736775918\u0026Signature=JVWdAuXAmT6Xea8RjkYdTDWLTkZiyjSLLR-LTtom5ZDhki-s2N15HGYTJ5fBLYuA2-lPA1ASXDgpCbMJK3aXDF4FsAxmwRjfUrD8803t7vCC6WTy0qsh1w7jqMIXGhC0j37gnO-R-KzkP~TM3tkA3CVIT86ormsPuku5MIWOrrqTRYvhbheEKKy40ApaDXZlQCTyQQYTp9~OuMSOhaYG3p94mthRTYC8fX5EtdLajZxdkkAKLklU3wwRzbHh2kFJcb15JRVIJO23piJA2U8nlDj9t3r1X1fbIRiQyjTwxGA8URPxICrJzXjlPzNdsgDQLL~Vb9VTaHMFbCdlpJQQtQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":2702,"name":"Immune response","url":"https://www.academia.edu/Documents/in/Immune_response"},{"id":9130,"name":"Chitosan","url":"https://www.academia.edu/Documents/in/Chitosan"},{"id":13621,"name":"Nanoparticles","url":"https://www.academia.edu/Documents/in/Nanoparticles"},{"id":63331,"name":"Hepatitis B","url":"https://www.academia.edu/Documents/in/Hepatitis_B"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":179934,"name":"Vaccination","url":"https://www.academia.edu/Documents/in/Vaccination"},{"id":279027,"name":"European","url":"https://www.academia.edu/Documents/in/European"},{"id":387484,"name":"Alginates","url":"https://www.academia.edu/Documents/in/Alginates"},{"id":678853,"name":"B Lymphocytes","url":"https://www.academia.edu/Documents/in/B_Lymphocytes"},{"id":990417,"name":"Recombinant Proteins","url":"https://www.academia.edu/Documents/in/Recombinant_Proteins"},{"id":1135812,"name":"Drug Compounding","url":"https://www.academia.edu/Documents/in/Drug_Compounding"},{"id":1334751,"name":"Hepatitis B Vaccine","url":"https://www.academia.edu/Documents/in/Hepatitis_B_Vaccine"},{"id":1529194,"name":"Hepatitis B Vaccines","url":"https://www.academia.edu/Documents/in/Hepatitis_B_Vaccines"},{"id":1944473,"name":"Oral Vaccination","url":"https://www.academia.edu/Documents/in/Oral_Vaccination"}],"urls":[{"id":2945776,"url":"http://www.sciencedirect.com/science/article/pii/S0928098707003284"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143032"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143032/Host_Cell_Phenotypic_Variability_Induced_by_Trypanosomatid_Parasite_Released_Immunomodulatory_Factors_Physiopathological_Implications"><img alt="Research paper thumbnail of Host Cell Phenotypic Variability Induced by Trypanosomatid-Parasite-Released Immunomodulatory Factors: Physiopathological Implications" class="work-thumbnail" src="https://attachments.academia-assets.com/48583885/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143032/Host_Cell_Phenotypic_Variability_Induced_by_Trypanosomatid_Parasite_Released_Immunomodulatory_Factors_Physiopathological_Implications">Host Cell Phenotypic Variability Induced by Trypanosomatid-Parasite-Released Immunomodulatory Factors: Physiopathological Implications</a></div><div class="wp-workCard_item"><span>Journal of Biomedicine and Biotechnology</span><span>, 2004</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The parasitic protozoa Trypanosoma cruzi and Leishmania sp release a variety of molecules into th...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The parasitic protozoa Trypanosoma cruzi and Leishmania sp release a variety of molecules into their mammalian hosts (ESA: excretory-secretory products). The effects of these ESA on the host cell function may participate in the establishment of a successful infection, in which the parasite persists for a sufficient period of time to complete its life cycle. A number of regulatory components or processes originating from the parasite that control or regulate the metabolism and the growth of host cell have been identified. The purpose of the present review is to analyze some of the current data related to the parasite ESA that interfere with the host cell physiology. Special attention is given to members of conserved protein families demonstrating remarkable diversity and plasticity of function (ie, glutathione S-transferases and related molecules; members of the trans-sialidase and mucin family; and members of the ribosomal protein family). The identification of parasite target molecules and the elucidation of their mode of action toward the host cell represents a step forward in efforts aimed at an immunotherapeutic or pharmacological control of parasitic infection.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="dbc3cfb4c2904aeb83f9ed40de26a963" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583885,"asset_id":7143032,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583885/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143032"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143032"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143032; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143032]").text(description); $(".js-view-count[data-work-id=7143032]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143032; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143032']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143032, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "dbc3cfb4c2904aeb83f9ed40de26a963" } } $('.js-work-strip[data-work-id=7143032]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143032,"title":"Host Cell Phenotypic Variability Induced by Trypanosomatid-Parasite-Released Immunomodulatory Factors: Physiopathological Implications","translated_title":"","metadata":{"grobid_abstract":"The parasitic protozoa Trypanosoma cruzi and Leishmania sp release a variety of molecules into their mammalian hosts (ESA: excretory-secretory products). The effects of these ESA on the host cell function may participate in the establishment of a successful infection, in which the parasite persists for a sufficient period of time to complete its life cycle. A number of regulatory components or processes originating from the parasite that control or regulate the metabolism and the growth of host cell have been identified. The purpose of the present review is to analyze some of the current data related to the parasite ESA that interfere with the host cell physiology. Special attention is given to members of conserved protein families demonstrating remarkable diversity and plasticity of function (ie, glutathione S-transferases and related molecules; members of the trans-sialidase and mucin family; and members of the ribosomal protein family). The identification of parasite target molecules and the elucidation of their mode of action toward the host cell represents a step forward in efforts aimed at an immunotherapeutic or pharmacological control of parasitic infection.","publication_date":{"day":null,"month":null,"year":2004,"errors":{}},"publication_name":"Journal of Biomedicine and Biotechnology","grobid_abstract_attachment_id":48583885},"translated_abstract":null,"internal_url":"https://www.academia.edu/7143032/Host_Cell_Phenotypic_Variability_Induced_by_Trypanosomatid_Parasite_Released_Immunomodulatory_Factors_Physiopathological_Implications","translated_internal_url":"","created_at":"2014-05-24T01:01:47.105-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583885,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583885/thumbnails/1.jpg","file_name":"280740.pdf","download_url":"https://www.academia.edu/attachments/48583885/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Host_Cell_Phenotypic_Variability_Induced.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583885/280740-libre.pdf?1473073947=\u0026response-content-disposition=attachment%3B+filename%3DHost_Cell_Phenotypic_Variability_Induced.pdf\u0026Expires=1736775918\u0026Signature=EgfDcuD-9n5uueqLIrmkfsB~C0M24Yn1M8w4OmfizVmc7XlziT5FAz0hQ4RbgwaBp-~a-xCK9DO-TTWu9zLnk11q6NKwbZqr4-en-vF-iLA9UM6S60zPkZTIlvgCOXfTdEJ5qIKqyZneDSwQN~QUcJLIyNG7vZ3nebzb3n46w368nUz42Tk2E~Mjr7TnEtKOb1OwOPcx6C9huqFHMzoxiuzY0joiFrxy04aMzhW4kMSqAAs0NWlbZo0zYNcATbRw1uSHRU1NCGN7Qyow5nolg-xzqOM3gXMlEkSWUvspU-~jwgYYUZGAUiE0gUGlWl7Qdku47I9RjdVmjaF6oGLNHw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Host_Cell_Phenotypic_Variability_Induced_by_Trypanosomatid_Parasite_Released_Immunomodulatory_Factors_Physiopathological_Implications","translated_slug":"","page_count":9,"language":"en","content_type":"Work","summary":"The parasitic protozoa Trypanosoma cruzi and Leishmania sp release a variety of molecules into their mammalian hosts (ESA: excretory-secretory products). The effects of these ESA on the host cell function may participate in the establishment of a successful infection, in which the parasite persists for a sufficient period of time to complete its life cycle. A number of regulatory components or processes originating from the parasite that control or regulate the metabolism and the growth of host cell have been identified. The purpose of the present review is to analyze some of the current data related to the parasite ESA that interfere with the host cell physiology. Special attention is given to members of conserved protein families demonstrating remarkable diversity and plasticity of function (ie, glutathione S-transferases and related molecules; members of the trans-sialidase and mucin family; and members of the ribosomal protein family). The identification of parasite target molecules and the elucidation of their mode of action toward the host cell represents a step forward in efforts aimed at an immunotherapeutic or pharmacological control of parasitic infection.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583885,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583885/thumbnails/1.jpg","file_name":"280740.pdf","download_url":"https://www.academia.edu/attachments/48583885/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Host_Cell_Phenotypic_Variability_Induced.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583885/280740-libre.pdf?1473073947=\u0026response-content-disposition=attachment%3B+filename%3DHost_Cell_Phenotypic_Variability_Induced.pdf\u0026Expires=1736775918\u0026Signature=EgfDcuD-9n5uueqLIrmkfsB~C0M24Yn1M8w4OmfizVmc7XlziT5FAz0hQ4RbgwaBp-~a-xCK9DO-TTWu9zLnk11q6NKwbZqr4-en-vF-iLA9UM6S60zPkZTIlvgCOXfTdEJ5qIKqyZneDSwQN~QUcJLIyNG7vZ3nebzb3n46w368nUz42Tk2E~Mjr7TnEtKOb1OwOPcx6C9huqFHMzoxiuzY0joiFrxy04aMzhW4kMSqAAs0NWlbZo0zYNcATbRw1uSHRU1NCGN7Qyow5nolg-xzqOM3gXMlEkSWUvspU-~jwgYYUZGAUiE0gUGlWl7Qdku47I9RjdVmjaF6oGLNHw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":923,"name":"Technology","url":"https://www.academia.edu/Documents/in/Technology"},{"id":1066,"name":"Biomedicine","url":"https://www.academia.edu/Documents/in/Biomedicine"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":222543,"name":"Biomed","url":"https://www.academia.edu/Documents/in/Biomed"}],"urls":[{"id":2945775,"url":"http://www.hindawi.com/journals/jbb/2004/280740.pdf"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143031"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143031/Recognition_of_Leishmania_Parasites_by_Innate_Immunity"><img alt="Research paper thumbnail of Recognition of Leishmania Parasites by Innate Immunity" class="work-thumbnail" src="https://attachments.academia-assets.com/48583957/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143031/Recognition_of_Leishmania_Parasites_by_Innate_Immunity">Recognition of Leishmania Parasites by Innate Immunity</a></div><div class="wp-workCard_item"><span>Immunology, Endocrine & Metabolic Agents - Medicinal Chemistry (formerly Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents)</span><span>, 2009</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The host innate immune system represents the first line of defense against invasive pathogens. Du...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The host innate immune system represents the first line of defense against invasive pathogens. During the crucial early stages of infection, the host innate immune system must be able to rapidly detect and respond to foreign pathogens, enabling an efficient and successful adaptative immune response. Leishmania parasites are obligate intracellular eukaryotic pathogens living inside cells of the mononuclear phagocytic system. Recent data has proven distinct roles of various phagocytic cells, such as neutrophils, macrophages and dendritic cells during Leishmania infection. There is growing evidence that Leishmania modifies antigen presentation, apoptosis and immunoregulatory functions on these cells, leading to persistent and chronic infection. At the molecular level, the Toll-like receptors (TLR) family is a major player in the early host-pathogen interaction. The TLRs expressed intracellularly or at the surface of the cells involved in the innate immune response recognize conserved structures on foreign pathogens, such as Leishmania, playing a pivotal role in triggering innate and adaptative immune responses. Nonetheless, the same TLRs can be considered as a potential strategic target used by these organisms for their own advantage. In this review, we discussed the findings on the cellular processes involved in the innate host defense against intracellular pathogens, focusing on the Leishmania infection, from the initial host-parasite interactions involved in the parasite recognition to the mechanisms employed to eliminate the pathogen, presenting new data on the role of TLR2 in visceral leishmaniasis.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="3f2d177a2294a9246b2369815de39a30" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583957,"asset_id":7143031,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583957/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143031"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143031"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143031; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143031]").text(description); $(".js-view-count[data-work-id=7143031]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143031; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143031']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143031, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "3f2d177a2294a9246b2369815de39a30" } } $('.js-work-strip[data-work-id=7143031]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143031,"title":"Recognition of Leishmania Parasites by Innate Immunity","translated_title":"","metadata":{"grobid_abstract":"The host innate immune system represents the first line of defense against invasive pathogens. 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The TLRs expressed intracellularly or at the surface of the cells involved in the innate immune response recognize conserved structures on foreign pathogens, such as Leishmania, playing a pivotal role in triggering innate and adaptative immune responses. Nonetheless, the same TLRs can be considered as a potential strategic target used by these organisms for their own advantage. In this review, we discussed the findings on the cellular processes involved in the innate host defense against intracellular pathogens, focusing on the Leishmania infection, from the initial host-parasite interactions involved in the parasite recognition to the mechanisms employed to eliminate the pathogen, presenting new data on the role of TLR2 in visceral leishmaniasis.","publication_date":{"day":null,"month":null,"year":2009,"errors":{}},"publication_name":"Immunology, Endocrine \u0026 Metabolic Agents - Medicinal Chemistry (formerly Current Medicinal Chemistry - Immunology, Endocrine \u0026 Metabolic Agents)","grobid_abstract_attachment_id":48583957},"translated_abstract":null,"internal_url":"https://www.academia.edu/7143031/Recognition_of_Leishmania_Parasites_by_Innate_Immunity","translated_internal_url":"","created_at":"2014-05-24T01:01:46.848-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583957,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583957/thumbnails/1.jpg","file_name":"Recognition_of_Leishmania_Parasites_by_I20160905-4206-1pcsvlu.pdf","download_url":"https://www.academia.edu/attachments/48583957/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Recognition_of_Leishmania_Parasites_by_I.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583957/Recognition_of_Leishmania_Parasites_by_I20160905-4206-1pcsvlu-libre.pdf?1473073953=\u0026response-content-disposition=attachment%3B+filename%3DRecognition_of_Leishmania_Parasites_by_I.pdf\u0026Expires=1736775918\u0026Signature=dfadb0Nn4R7xIUO-TzJ0eZ76LO~Fblxl644bV5C-lCmiV-N1t4QgwAvJmZU9Ok2c0VeXXq2ewjwj2vwcAslwLjHEOWgetT9y4yppnr0SzZAJckgezTjgOC0RVOGji18~Ygzzmf8XJWz614O8PuxAc28O2Uezw5pHYEzc9i1wK6fG1sfx5RYRVetSMs3b8IAFhgktDIjykGPe0CF3hKTf-U47l~2aVPGCqHlQtBFvfcZxqo2c7i9Va0DyOhL0wdXpuHWbj6elgX30e9dV-eTR9lLoPDsjqkzKD~VeyVyVuLJqVY~twf4OW2nKnSrYRvp~2axAynECQnaOPoDyqccFpQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Recognition_of_Leishmania_Parasites_by_Innate_Immunity","translated_slug":"","page_count":18,"language":"en","content_type":"Work","summary":"The host innate immune system represents the first line of defense against invasive pathogens. 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The TLRs expressed intracellularly or at the surface of the cells involved in the innate immune response recognize conserved structures on foreign pathogens, such as Leishmania, playing a pivotal role in triggering innate and adaptative immune responses. Nonetheless, the same TLRs can be considered as a potential strategic target used by these organisms for their own advantage. In this review, we discussed the findings on the cellular processes involved in the innate host defense against intracellular pathogens, focusing on the Leishmania infection, from the initial host-parasite interactions involved in the parasite recognition to the mechanisms employed to eliminate the pathogen, presenting new data on the role of TLR2 in visceral leishmaniasis.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583957,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583957/thumbnails/1.jpg","file_name":"Recognition_of_Leishmania_Parasites_by_I20160905-4206-1pcsvlu.pdf","download_url":"https://www.academia.edu/attachments/48583957/download_file?st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Recognition_of_Leishmania_Parasites_by_I.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583957/Recognition_of_Leishmania_Parasites_by_I20160905-4206-1pcsvlu-libre.pdf?1473073953=\u0026response-content-disposition=attachment%3B+filename%3DRecognition_of_Leishmania_Parasites_by_I.pdf\u0026Expires=1736775918\u0026Signature=dfadb0Nn4R7xIUO-TzJ0eZ76LO~Fblxl644bV5C-lCmiV-N1t4QgwAvJmZU9Ok2c0VeXXq2ewjwj2vwcAslwLjHEOWgetT9y4yppnr0SzZAJckgezTjgOC0RVOGji18~Ygzzmf8XJWz614O8PuxAc28O2Uezw5pHYEzc9i1wK6fG1sfx5RYRVetSMs3b8IAFhgktDIjykGPe0CF3hKTf-U47l~2aVPGCqHlQtBFvfcZxqo2c7i9Va0DyOhL0wdXpuHWbj6elgX30e9dV-eTR9lLoPDsjqkzKD~VeyVyVuLJqVY~twf4OW2nKnSrYRvp~2axAynECQnaOPoDyqccFpQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":24706,"name":"Innate immunity","url":"https://www.academia.edu/Documents/in/Innate_immunity"},{"id":126964,"name":"Endocrine","url":"https://www.academia.edu/Documents/in/Endocrine"}],"urls":[{"id":2945774,"url":"http://openurl.ingenta.com/content/xref?genre=article\u0026issn=1871-5222\u0026volume=9\u0026issue=2\u0026spage=106"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143030"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143030/Effect_of_anti_inflammatory_drugs_on_splenocyte_membrane_fluidity"><img alt="Research paper thumbnail of Effect of anti-inflammatory drugs on splenocyte membrane fluidity" class="work-thumbnail" src="https://attachments.academia-assets.com/48583897/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143030/Effect_of_anti_inflammatory_drugs_on_splenocyte_membrane_fluidity">Effect of anti-inflammatory drugs on splenocyte membrane fluidity</a></div><div class="wp-workCard_item"><span>Analytical Biochemistry</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">In this study, Xuorescence anisotropy measurements were performed using the Xuorescent probe 1,6-...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">In this study, Xuorescence anisotropy measurements were performed using the Xuorescent probe 1,6-diphenyl-1,3,5-hexatriene to investigate the eVects on membrane Xuidity resulting from the interaction between nonsteroidal anti-inXammatory drugs (NSA-IDs)-indomethacin, diclofenac, piroxicam, tenoxicam, indoprofen, clonixin, and etodolac-and mouse splenocyte membranes. This study was performed in splenocyte membranes because most of the Xuidity studies have been performed in membrane models; thus, clear correlations of the pharmacological action of drugs with molecular eVects at the cellular membrane level were lacking. Besides providing a basis for studying the molecular mechanism of pharmacological action of NSAIDs, this research provides a data analysis of steady-state anisotropy measurements, taking into account that the probe itself strongly inXuences the data given that this problem is usually overlooked. Results show that the anti-inXammatory drugs indomethacin, diclofenac, piroxicam, and tenoxicam increase the membrane Xuidity in a concentration-dependent manner. Their order of eVectiveness reXected in their respective IC 50 values (concentration of each NSAID required to increase the Xuidizing eVect ratio by 50%) is as follows: tenoxicam > piroxicam > indomethacin > clonixin. For the other drugs, the perturbation in membrane Xuidity is not evident under these circumstances. </span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="3319b971e112a72e47a80d72b4fe3932" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583897,"asset_id":7143030,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583897/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143030"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143030"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143030; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143030]").text(description); $(".js-view-count[data-work-id=7143030]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143030; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143030']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143030, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "3319b971e112a72e47a80d72b4fe3932" } } $('.js-work-strip[data-work-id=7143030]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143030,"title":"Effect of anti-inflammatory drugs on splenocyte membrane fluidity","translated_title":"","metadata":{"grobid_abstract":"In this study, Xuorescence anisotropy measurements were performed using the Xuorescent probe 1,6-diphenyl-1,3,5-hexatriene to investigate the eVects on membrane Xuidity resulting from the interaction between nonsteroidal anti-inXammatory drugs (NSA-IDs)-indomethacin, diclofenac, piroxicam, tenoxicam, indoprofen, clonixin, and etodolac-and mouse splenocyte membranes. This study was performed in splenocyte membranes because most of the Xuidity studies have been performed in membrane models; thus, clear correlations of the pharmacological action of drugs with molecular eVects at the cellular membrane level were lacking. Besides providing a basis for studying the molecular mechanism of pharmacological action of NSAIDs, this research provides a data analysis of steady-state anisotropy measurements, taking into account that the probe itself strongly inXuences the data given that this problem is usually overlooked. Results show that the anti-inXammatory drugs indomethacin, diclofenac, piroxicam, and tenoxicam increase the membrane Xuidity in a concentration-dependent manner. Their order of eVectiveness reXected in their respective IC 50 values (concentration of each NSAID required to increase the Xuidizing eVect ratio by 50%) is as follows: tenoxicam \u003e piroxicam \u003e indomethacin \u003e clonixin. For the other drugs, the perturbation in membrane Xuidity is not evident under these circumstances. ","publication_date":{"day":null,"month":null,"year":2005,"errors":{}},"publication_name":"Analytical Biochemistry","grobid_abstract_attachment_id":48583897},"translated_abstract":null,"internal_url":"https://www.academia.edu/7143030/Effect_of_anti_inflammatory_drugs_on_splenocyte_membrane_fluidity","translated_internal_url":"","created_at":"2014-05-24T01:01:46.515-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583897,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583897/thumbnails/1.jpg","file_name":"j.ab.2004.12.02320160905-26881-3567ip.pdf","download_url":"https://www.academia.edu/attachments/48583897/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Effect_of_anti_inflammatory_drugs_on_spl.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583897/j.ab.2004.12.02320160905-26881-3567ip-libre.pdf?1473073946=\u0026response-content-disposition=attachment%3B+filename%3DEffect_of_anti_inflammatory_drugs_on_spl.pdf\u0026Expires=1736775919\u0026Signature=VoMKScCUNXimEkirSDSa~TyeuZhyEBR3mae4Dt1DBomMS6yH8d831Ae4ERZdJiOG-FLgcBM9aKFflk8yusfFg-Ot16X2YDb6pHADordeCb4WRbT6kQbVS-CP2ObhtuvOUaqYeAYJyO2FEJ4~U4GV7pjWCfp2AypDxErezCPe4wqsqgIQOjoxgprlJ1911CwaFR8PzpcZlBnchZggVFsierXyhi50auiBlHglnlLlIDght~yjZOze27ylNFNBGzs1GNOkEwkUJm6f4NRud0HpOq2b0w6N5tBwaaq~KgN61CbrwQ~jookqRQqAD~SfM9Uia5UnMryR36bfZZQ-jpBsLg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Effect_of_anti_inflammatory_drugs_on_splenocyte_membrane_fluidity","translated_slug":"","page_count":6,"language":"en","content_type":"Work","summary":"In this study, Xuorescence anisotropy measurements were performed using the Xuorescent probe 1,6-diphenyl-1,3,5-hexatriene to investigate the eVects on membrane Xuidity resulting from the interaction between nonsteroidal anti-inXammatory drugs (NSA-IDs)-indomethacin, diclofenac, piroxicam, tenoxicam, indoprofen, clonixin, and etodolac-and mouse splenocyte membranes. This study was performed in splenocyte membranes because most of the Xuidity studies have been performed in membrane models; thus, clear correlations of the pharmacological action of drugs with molecular eVects at the cellular membrane level were lacking. Besides providing a basis for studying the molecular mechanism of pharmacological action of NSAIDs, this research provides a data analysis of steady-state anisotropy measurements, taking into account that the probe itself strongly inXuences the data given that this problem is usually overlooked. Results show that the anti-inXammatory drugs indomethacin, diclofenac, piroxicam, and tenoxicam increase the membrane Xuidity in a concentration-dependent manner. Their order of eVectiveness reXected in their respective IC 50 values (concentration of each NSAID required to increase the Xuidizing eVect ratio by 50%) is as follows: tenoxicam \u003e piroxicam \u003e indomethacin \u003e clonixin. For the other drugs, the perturbation in membrane Xuidity is not evident under these circumstances. ","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583897,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583897/thumbnails/1.jpg","file_name":"j.ab.2004.12.02320160905-26881-3567ip.pdf","download_url":"https://www.academia.edu/attachments/48583897/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Effect_of_anti_inflammatory_drugs_on_spl.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583897/j.ab.2004.12.02320160905-26881-3567ip-libre.pdf?1473073946=\u0026response-content-disposition=attachment%3B+filename%3DEffect_of_anti_inflammatory_drugs_on_spl.pdf\u0026Expires=1736775919\u0026Signature=VoMKScCUNXimEkirSDSa~TyeuZhyEBR3mae4Dt1DBomMS6yH8d831Ae4ERZdJiOG-FLgcBM9aKFflk8yusfFg-Ot16X2YDb6pHADordeCb4WRbT6kQbVS-CP2ObhtuvOUaqYeAYJyO2FEJ4~U4GV7pjWCfp2AypDxErezCPe4wqsqgIQOjoxgprlJ1911CwaFR8PzpcZlBnchZggVFsierXyhi50auiBlHglnlLlIDght~yjZOze27ylNFNBGzs1GNOkEwkUJm6f4NRud0HpOq2b0w6N5tBwaaq~KgN61CbrwQ~jookqRQqAD~SfM9Uia5UnMryR36bfZZQ-jpBsLg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":524,"name":"Analytical Chemistry","url":"https://www.academia.edu/Documents/in/Analytical_Chemistry"},{"id":4205,"name":"Data Analysis","url":"https://www.academia.edu/Documents/in/Data_Analysis"},{"id":18529,"name":"Fluorescent Dyes and Reagents","url":"https://www.academia.edu/Documents/in/Fluorescent_Dyes_and_Reagents"},{"id":35637,"name":"Molecular Mechanics","url":"https://www.academia.edu/Documents/in/Molecular_Mechanics"},{"id":49018,"name":"Spleen","url":"https://www.academia.edu/Documents/in/Spleen"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":132569,"name":"Analytical","url":"https://www.academia.edu/Documents/in/Analytical"},{"id":204350,"name":"Anti-inflammatory agents","url":"https://www.academia.edu/Documents/in/Anti-inflammatory_agents"},{"id":234860,"name":"Steady state","url":"https://www.academia.edu/Documents/in/Steady_state"},{"id":452441,"name":"Fluorescent probes","url":"https://www.academia.edu/Documents/in/Fluorescent_probes"},{"id":539887,"name":"Fluorescence polarization","url":"https://www.academia.edu/Documents/in/Fluorescence_polarization"},{"id":639922,"name":"Fluorescence anisotropy","url":"https://www.academia.edu/Documents/in/Fluorescence_anisotropy"},{"id":806387,"name":"Analytical Biochemistry","url":"https://www.academia.edu/Documents/in/Analytical_Biochemistry"},{"id":1465015,"name":"Membrane Fluidity","url":"https://www.academia.edu/Documents/in/Membrane_Fluidity"},{"id":1681026,"name":"Biochemistry and cell biology","url":"https://www.academia.edu/Documents/in/Biochemistry_and_cell_biology"},{"id":2468093,"name":"Cell Membrane","url":"https://www.academia.edu/Documents/in/Cell_Membrane"}],"urls":[{"id":2945773,"url":"http://www.sciencedirect.com/science/article/pii/S0003269705000035"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143029"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143029/Characterization_of_the_anti_Leishmania_effect_induced_by_cisplatin_an_anticancer_drug"><img alt="Research paper thumbnail of Characterization of the anti- Leishmania effect induced by cisplatin, an anticancer drug" class="work-thumbnail" src="https://attachments.academia-assets.com/48583900/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143029/Characterization_of_the_anti_Leishmania_effect_induced_by_cisplatin_an_anticancer_drug">Characterization of the anti- Leishmania effect induced by cisplatin, an anticancer drug</a></div><div class="wp-workCard_item"><span>Acta Tropica</span><span>, 2007</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The cis-diamminedichloroplatinum(II), known as cis-DDP or cisplatin is a widely used drug in canc...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The cis-diamminedichloroplatinum(II), known as cis-DDP or cisplatin is a widely used drug in cancer chemotherapy. Although a recent study has shown the anti-Leishmania activity of some cis-DDP derivatives, the cytotoxic properties were measured only on promastigotes, the insect vector form of the parasite. In this study the effect of cis-DDP on promastigotes and amastigotes, the vertebrate stage of the parasite is reported. The IC 50 , determined by flow cytometry, after 72 h of drug incubation was four times higher, 7.73 ± 1.03 M in the case of promastigotes compared to axenic amastigotes, 1.88 ± 0.10 M. In intracellular amastigotes the IC 50 , determined by counting the parasite index was 1.85 ± 0.22 M. By using flow cytometry, two patterns of cell cycle changes was observed: cis-DDP treated promastigotes and amastigotes accumulated in S phase and G2 phase, respectively. The cis-DDP response was also found to involve an "apoptosis-like" death of both promastigotes and amastigotes. However, DNA fragmentation was only detected in promastigote forms. In contrast mitochondrial transmembrane potential loss was observed for both stages of the parasite. Upon incubation of parasites with the drug an increase on GSH and GSSG levels and reactive oxygen species could be detected in the case of promastigote. Moreover, a slight increase of GSH level was detected on amastigote form. Taken together, these observations indicate that amastigotes are more sensitive to cis-DDP when compared to promastigotes. However, the signaling pathways leading to cell death could be different.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="15219008d08ca50dc378eb820181e5c2" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583900,"asset_id":7143029,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583900/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143029"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143029"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143029; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143029]").text(description); $(".js-view-count[data-work-id=7143029]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143029; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143029']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143029, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "15219008d08ca50dc378eb820181e5c2" } } $('.js-work-strip[data-work-id=7143029]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143029,"title":"Characterization of the anti- Leishmania effect induced by cisplatin, an anticancer drug","translated_title":"","metadata":{"ai_title_tag":"Cisplatin's Differential Anti-Leishmania Effects on Life Stages","grobid_abstract":"The cis-diamminedichloroplatinum(II), known as cis-DDP or cisplatin is a widely used drug in cancer chemotherapy. Although a recent study has shown the anti-Leishmania activity of some cis-DDP derivatives, the cytotoxic properties were measured only on promastigotes, the insect vector form of the parasite. In this study the effect of cis-DDP on promastigotes and amastigotes, the vertebrate stage of the parasite is reported. The IC 50 , determined by flow cytometry, after 72 h of drug incubation was four times higher, 7.73 ± 1.03 M in the case of promastigotes compared to axenic amastigotes, 1.88 ± 0.10 M. In intracellular amastigotes the IC 50 , determined by counting the parasite index was 1.85 ± 0.22 M. By using flow cytometry, two patterns of cell cycle changes was observed: cis-DDP treated promastigotes and amastigotes accumulated in S phase and G2 phase, respectively. The cis-DDP response was also found to involve an \"apoptosis-like\" death of both promastigotes and amastigotes. However, DNA fragmentation was only detected in promastigote forms. In contrast mitochondrial transmembrane potential loss was observed for both stages of the parasite. Upon incubation of parasites with the drug an increase on GSH and GSSG levels and reactive oxygen species could be detected in the case of promastigote. Moreover, a slight increase of GSH level was detected on amastigote form. Taken together, these observations indicate that amastigotes are more sensitive to cis-DDP when compared to promastigotes. However, the signaling pathways leading to cell death could be different.","publication_date":{"day":null,"month":null,"year":2007,"errors":{}},"publication_name":"Acta Tropica","grobid_abstract_attachment_id":48583900},"translated_abstract":null,"internal_url":"https://www.academia.edu/7143029/Characterization_of_the_anti_Leishmania_effect_induced_by_cisplatin_an_anticancer_drug","translated_internal_url":"","created_at":"2014-05-24T01:01:46.141-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583900,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583900/thumbnails/1.jpg","file_name":"j.actatropica.2007.05.01720160905-19689-1chtuzx.pdf","download_url":"https://www.academia.edu/attachments/48583900/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Characterization_of_the_anti_Leishmania.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583900/j.actatropica.2007.05.01720160905-19689-1chtuzx-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DCharacterization_of_the_anti_Leishmania.pdf\u0026Expires=1736775919\u0026Signature=f7WRYgrH8gddZw-jYZfp1cl7v3mWAHVEOyWy2wx5CP1boyZ~magasZRer3InULt7UP4b2EDPoI7nSFTU3XIaAZXk6TIR--pMXR0CNP6wYTH4lWZujRAB7FdydPyiH7VFKkPyieI61H4BK3iPABEhivMmhG4u0S2gvTQkTQr7b4RFAiPXGLmeRnsfgWeVZmKGtqP0qDq-E8IW~d3Gc0U~jzjThRqxALILl27mAxG~qtfh4jMTI4e7lUY0DI3-wMZH7nUlSsuGnZO5WVf1BEqj1rb5Bzr4TH5UIyRZfTj8rXOL0E77hAFdItg~d-Esk9-EYemTEVM4QERrdt9zFU1wrg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Characterization_of_the_anti_Leishmania_effect_induced_by_cisplatin_an_anticancer_drug","translated_slug":"","page_count":9,"language":"en","content_type":"Work","summary":"The cis-diamminedichloroplatinum(II), known as cis-DDP or cisplatin is a widely used drug in cancer chemotherapy. Although a recent study has shown the anti-Leishmania activity of some cis-DDP derivatives, the cytotoxic properties were measured only on promastigotes, the insect vector form of the parasite. In this study the effect of cis-DDP on promastigotes and amastigotes, the vertebrate stage of the parasite is reported. The IC 50 , determined by flow cytometry, after 72 h of drug incubation was four times higher, 7.73 ± 1.03 M in the case of promastigotes compared to axenic amastigotes, 1.88 ± 0.10 M. In intracellular amastigotes the IC 50 , determined by counting the parasite index was 1.85 ± 0.22 M. By using flow cytometry, two patterns of cell cycle changes was observed: cis-DDP treated promastigotes and amastigotes accumulated in S phase and G2 phase, respectively. The cis-DDP response was also found to involve an \"apoptosis-like\" death of both promastigotes and amastigotes. However, DNA fragmentation was only detected in promastigote forms. In contrast mitochondrial transmembrane potential loss was observed for both stages of the parasite. Upon incubation of parasites with the drug an increase on GSH and GSSG levels and reactive oxygen species could be detected in the case of promastigote. Moreover, a slight increase of GSH level was detected on amastigote form. Taken together, these observations indicate that amastigotes are more sensitive to cis-DDP when compared to promastigotes. However, the signaling pathways leading to cell death could be different.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583900,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583900/thumbnails/1.jpg","file_name":"j.actatropica.2007.05.01720160905-19689-1chtuzx.pdf","download_url":"https://www.academia.edu/attachments/48583900/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Characterization_of_the_anti_Leishmania.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583900/j.actatropica.2007.05.01720160905-19689-1chtuzx-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DCharacterization_of_the_anti_Leishmania.pdf\u0026Expires=1736775919\u0026Signature=f7WRYgrH8gddZw-jYZfp1cl7v3mWAHVEOyWy2wx5CP1boyZ~magasZRer3InULt7UP4b2EDPoI7nSFTU3XIaAZXk6TIR--pMXR0CNP6wYTH4lWZujRAB7FdydPyiH7VFKkPyieI61H4BK3iPABEhivMmhG4u0S2gvTQkTQr7b4RFAiPXGLmeRnsfgWeVZmKGtqP0qDq-E8IW~d3Gc0U~jzjThRqxALILl27mAxG~qtfh4jMTI4e7lUY0DI3-wMZH7nUlSsuGnZO5WVf1BEqj1rb5Bzr4TH5UIyRZfTj8rXOL0E77hAFdItg~d-Esk9-EYemTEVM4QERrdt9zFU1wrg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":6599,"name":"Flow Cytometry","url":"https://www.academia.edu/Documents/in/Flow_Cytometry"},{"id":9113,"name":"Cell Cycle","url":"https://www.academia.edu/Documents/in/Cell_Cycle"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":82978,"name":"Reactive Oxygen Species","url":"https://www.academia.edu/Documents/in/Reactive_Oxygen_Species"},{"id":112576,"name":"Cell Death","url":"https://www.academia.edu/Documents/in/Cell_Death"},{"id":118450,"name":"Glutathione","url":"https://www.academia.edu/Documents/in/Glutathione"},{"id":128004,"name":"Visceral Leishmaniasis","url":"https://www.academia.edu/Documents/in/Visceral_Leishmaniasis"},{"id":163353,"name":"Cancer Chemotherapy","url":"https://www.academia.edu/Documents/in/Cancer_Chemotherapy"},{"id":276781,"name":"Cisplatin","url":"https://www.academia.edu/Documents/in/Cisplatin"},{"id":749302,"name":"Indexation","url":"https://www.academia.edu/Documents/in/Indexation"},{"id":789996,"name":"Leishmania infantum","url":"https://www.academia.edu/Documents/in/Leishmania_infantum"},{"id":1212103,"name":"Antineoplastic Agents","url":"https://www.academia.edu/Documents/in/Antineoplastic_Agents"},{"id":1777414,"name":"Anticancer Drug","url":"https://www.academia.edu/Documents/in/Anticancer_Drug"},{"id":2256666,"name":"DNA fragmentation","url":"https://www.academia.edu/Documents/in/DNA_fragmentation"}],"urls":[{"id":2945772,"url":"http://www.sciencedirect.com/science/article/pii/S0001706X07001374"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> </div><div class="profile--tab_content_container js-tab-pane tab-pane" data-section-id="1462592" id="papers"><div class="js-work-strip profile--work_container" data-work-id="7143049"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143049/Differential_effects_of_polyamine_derivative_compounds_against_Leishmania_infantum_promastigotes_and_axenic_amastigotes"><img alt="Research paper thumbnail of Differential effects of polyamine derivative compounds against Leishmania infantum promastigotes and axenic amastigotes" class="work-thumbnail" src="https://attachments.academia-assets.com/48583896/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143049/Differential_effects_of_polyamine_derivative_compounds_against_Leishmania_infantum_promastigotes_and_axenic_amastigotes">Differential effects of polyamine derivative compounds against Leishmania infantum promastigotes and axenic amastigotes</a></div><div class="wp-workCard_item"><span>International Journal for Parasitology</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The natural polyamines are ubiquitous polycationic compounds that play important biological funct...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The natural polyamines are ubiquitous polycationic compounds that play important biological functions in cell growth and differentiation. In the case of protozoan species that are causative agents of important human diseases such as Leishmaniasis, an exogenous supply of polyamines supports parasite proliferation. In the present study, we have investigated the effect of three polyamine derivatives, (namely bisnaphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd) and spermine (BNIPSpm)), on the proliferative stages of Leishmania infantum, the causative agent of visceral leishmaniasis in the Mediterranean basin. A significant reduction of promastigotes and axenic amastigotes growth was observed in the presence of increasing concentrations of the drugs, although the mechanisms leading to the parasite growth arrest seems to be different. Indeed, by using a number of biochemical approaches to analyse the alterations that occurred during early stages of parasite-drug interaction (i.e. membrane phosphatidylserine exposure measured by annexin V binding, DNA fragmentation, deoxynucleotidyltranferase-mediated dUTP end labelin (TUNEL), mitochondrial transmembrane potential loss), we showed that the drugs had the capacity to induce the death of promastigotes by a mechanism that shares many features with metazoan apoptosis. Surprisingly, the amastigotes did not behave in a similar way to promastigotes. The drug inhibitory effect on amastigotes growth and the absence of propidium iodide labelling may suggest that the compounds are acting as cytostatic substances. Although, the mechanisms of action of these compounds have yet to be elucidated, the above data show for the first time that polyamine derivatives may act differentially on the Leishmania parasite stages. Further chemical modifications are needed to make the polyamine derivatives as well as other analogues able to target the amastigote stage of the parasite. q</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="4794fb7e519060791c6f32ccf48ecb89" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583896,"asset_id":7143049,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583896/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143049"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143049"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143049; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143049]").text(description); $(".js-view-count[data-work-id=7143049]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143049; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143049']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143049, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "4794fb7e519060791c6f32ccf48ecb89" } } $('.js-work-strip[data-work-id=7143049]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143049,"title":"Differential effects of polyamine derivative compounds against Leishmania infantum promastigotes and axenic amastigotes","translated_title":"","metadata":{"grobid_abstract":"The natural polyamines are ubiquitous polycationic compounds that play important biological functions in cell growth and differentiation. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143048"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143048/Impact_of_Continuous_Axenic_Cultivation_in_Leishmania_infantum_Virulence"><img alt="Research paper thumbnail of Impact of Continuous Axenic Cultivation in Leishmania infantum Virulence" class="work-thumbnail" src="https://attachments.academia-assets.com/48583915/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143048/Impact_of_Continuous_Axenic_Cultivation_in_Leishmania_infantum_Virulence">Impact of Continuous Axenic Cultivation in Leishmania infantum Virulence</a></div><div class="wp-workCard_item"><span>PLOS Neglected Tropical Diseases</span><span>, 2012</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Experimental infections with visceral Leishmania spp. are frequently performed referring to stati...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Experimental infections with visceral Leishmania spp. are frequently performed referring to stationary parasite cultures that are comprised of a mixture of metacyclic and non-metacyclic parasites often with little regard to time of culture and metacyclic purification. This may lead to misleading or irreproducible experimental data. It is known that the maintenance of Leishmania spp. in vitro results in a progressive loss of virulence that can be reverted by passage in a mammalian host. In the present study, we aimed to characterize the loss of virulence in culture comparing the in vitro and in vivo infection and immunological profile of L. infantum stationary promastigotes submitted to successive periods of in vitro cultivation. To evaluate the effect of axenic in vitro culture in parasite virulence, we submitted L. infantum promastigotes to 4, 21 or 31 successive in vitro passages. Our results demonstrated a rapid and significant loss of parasite virulence when parasites are sustained in axenic culture. Strikingly, the parasite capacity to modulate macrophage activation decreased significantly with the augmentation of the number of in vitro passages. We validated these in vitro observations using an experimental murine model of infection. A significant correlation was found between higher parasite burdens and lower number of in vitro passages in infected Balb/c mice. Furthermore, we have demonstrated that the virulence deficit caused by successive in vitro passages results from an inadequate capacity to differentiate into amastigote forms. In conclusion, our data demonstrated that the use of parasites with distinct periods of axenic in vitro culture induce distinct infection rates and immunological responses and correlated this phenotype with a rapid loss of promastigote differentiation capacity. These results highlight the need for a standard operating protocol (SOP) when studying Leishmania species.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="6a9c6d129ead05d2d3bdd30be4d0ba51" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583915,"asset_id":7143048,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583915/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143048"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143048"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143048; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143048]").text(description); $(".js-view-count[data-work-id=7143048]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143048; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143048']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143048, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "6a9c6d129ead05d2d3bdd30be4d0ba51" } } $('.js-work-strip[data-work-id=7143048]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143048,"title":"Impact of Continuous Axenic Cultivation in Leishmania infantum Virulence","translated_title":"","metadata":{"grobid_abstract":"Experimental infections with visceral Leishmania spp. are frequently performed referring to stationary parasite cultures that are comprised of a mixture of metacyclic and non-metacyclic parasites often with little regard to time of culture and metacyclic purification. 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A significant correlation was found between higher parasite burdens and lower number of in vitro passages in infected Balb/c mice. Furthermore, we have demonstrated that the virulence deficit caused by successive in vitro passages results from an inadequate capacity to differentiate into amastigote forms. In conclusion, our data demonstrated that the use of parasites with distinct periods of axenic in vitro culture induce distinct infection rates and immunological responses and correlated this phenotype with a rapid loss of promastigote differentiation capacity. 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This may lead to misleading or irreproducible experimental data. It is known that the maintenance of Leishmania spp. in vitro results in a progressive loss of virulence that can be reverted by passage in a mammalian host. In the present study, we aimed to characterize the loss of virulence in culture comparing the in vitro and in vivo infection and immunological profile of L. infantum stationary promastigotes submitted to successive periods of in vitro cultivation. To evaluate the effect of axenic in vitro culture in parasite virulence, we submitted L. infantum promastigotes to 4, 21 or 31 successive in vitro passages. Our results demonstrated a rapid and significant loss of parasite virulence when parasites are sustained in axenic culture. Strikingly, the parasite capacity to modulate macrophage activation decreased significantly with the augmentation of the number of in vitro passages. We validated these in vitro observations using an experimental murine model of infection. A significant correlation was found between higher parasite burdens and lower number of in vitro passages in infected Balb/c mice. Furthermore, we have demonstrated that the virulence deficit caused by successive in vitro passages results from an inadequate capacity to differentiate into amastigote forms. In conclusion, our data demonstrated that the use of parasites with distinct periods of axenic in vitro culture induce distinct infection rates and immunological responses and correlated this phenotype with a rapid loss of promastigote differentiation capacity. These results highlight the need for a standard operating protocol (SOP) when studying Leishmania species.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583915,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583915/thumbnails/1.jpg","file_name":"Impact_of_continuous_axenic_cultivation_20160905-23542-g1leo1.pdf","download_url":"https://www.academia.edu/attachments/48583915/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Impact_of_Continuous_Axenic_Cultivation.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583915/Impact_of_continuous_axenic_cultivation_20160905-23542-g1leo1-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DImpact_of_Continuous_Axenic_Cultivation.pdf\u0026Expires=1736775918\u0026Signature=N3xajqY2-01Y1hhRgV3FNknhovcYgB9lbw8Yn2Jk4J-DwsiRUT~ZsodOogaWf9Vh1aCZIgI5rlQ4~fFfAMugjgm9NbdiR0rGPgmUuSvd5eD0Py9WpVcW3iCbl49lO5EvFOXLOhbNxcosbRDJ02xjzfR6LFWr5MDDF-BSNXvZXMmpHReRG0ePlkzbeqLYmUxt7AVJ9I5BgMVQ6E8yg50d-kw9B1v9t3z~~mdCYmi2tlMsmMbt03CFY5gh1IoOmQgfUuL~FeJPdEr9NE6c-c6qLqwRBw9saBaz~~3C2Qm7U0zTEzwYGiYKoB0twMcSbm~cSklKKkmPPjusF4oqfHOhdA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":17491,"name":"Macrophages","url":"https://www.academia.edu/Documents/in/Macrophages"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":52873,"name":"Virulence","url":"https://www.academia.edu/Documents/in/Virulence"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":128004,"name":"Visceral Leishmaniasis","url":"https://www.academia.edu/Documents/in/Visceral_Leishmaniasis"},{"id":238630,"name":"Experimental Infection","url":"https://www.academia.edu/Documents/in/Experimental_Infection"},{"id":413750,"name":"In vitro culture","url":"https://www.academia.edu/Documents/in/In_vitro_culture"},{"id":789996,"name":"Leishmania infantum","url":"https://www.academia.edu/Documents/in/Leishmania_infantum"},{"id":951639,"name":"Murine Model","url":"https://www.academia.edu/Documents/in/Murine_Model"},{"id":1120502,"name":"Experimental Data","url":"https://www.academia.edu/Documents/in/Experimental_Data"}],"urls":[{"id":2945791,"url":"http://dx.doi.org/10.1371/journal.pntd.0001469"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143047"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143047/Leishmania_cytosolic_silent_information_regulatory_protein_2_deacetylase_induces_murine_B_cell_differentiation_and_in_vivo_production_of_specific_antibodies"><img alt="Research paper thumbnail of Leishmania cytosolic silent information regulatory protein 2 deacetylase induces murine B-cell differentiation and in vivo production of specific antibodies" class="work-thumbnail" src="https://attachments.academia-assets.com/48583901/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143047/Leishmania_cytosolic_silent_information_regulatory_protein_2_deacetylase_induces_murine_B_cell_differentiation_and_in_vivo_production_of_specific_antibodies">Leishmania cytosolic silent information regulatory protein 2 deacetylase induces murine B-cell differentiation and in vivo production of specific antibodies</a></div><div class="wp-workCard_item"><span>Immunology</span><span>, 2006</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">In previous studies, we identified a gene product belonging to the silent information regulatory ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">In previous studies, we identified a gene product belonging to the silent information regulatory 2 protein (SIR2) family. This protein is expressed by all Leishmania species so far examined (L. major, L. infantum, L. amazonensis, L. mexicana) and found to be crucial for parasite survival and virulence. In the present study, we investigated whether a Leishmania SIR2 recombinant protein (LmSIR2) would affect T- and B-cell functions in a murine model. In vitro treatment of spleen cells from normal BALB/c mice with LmSIR2 showed increased expression of CD69 on B cells. This effect was not abolished by the addition of polymyxin B. Intravenous injection of LmSIR2 into BALB/c mice induced increased spleen B cell number by a factor of about ≈1·6, whereas no modification occurred at the level of CD4+ and CD8+ cells. Furthermore, intraperitoneal injection of LmSIR2 alone without adjuvant into BALB/c mice or nude mice triggered the production of elevated levels of LmSIR2-specific antibodies. The analysis of specific isotype profiles showed a predominance of immunoglobulin G1 (IgG1) and IgG2a antibody responses in BALB/c mice, and IgM in nude mice. Moreover, the anti-LmSIR2 mouse antibodies in the presence of complement induced the in vitro lysis of L. infantum amastigotes. In the absence of complement, the antibodies induced significant inhibition of amastigotes developpement inside macrophages. Together, the current study provides the first evidence that a Leishmania protein belonging to the SIR2 family may play a role in the regulation of immune response through its capacity to trigger B-cell effector function.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="2ab547e26b2268331e1f58530be4c186" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583901,"asset_id":7143047,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583901/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143047"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143047"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143047; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143047]").text(description); $(".js-view-count[data-work-id=7143047]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143047; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143047']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143047, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "2ab547e26b2268331e1f58530be4c186" } } $('.js-work-strip[data-work-id=7143047]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143047,"title":"Leishmania cytosolic silent information regulatory protein 2 deacetylase induces murine B-cell differentiation and in vivo production of specific antibodies","translated_title":"","metadata":{"abstract":"In previous studies, we identified a gene product belonging to the silent information regulatory 2 protein (SIR2) family. This protein is expressed by all Leishmania species so far examined (L. major, L. infantum, L. amazonensis, L. mexicana) and found to be crucial for parasite survival and virulence. In the present study, we investigated whether a Leishmania SIR2 recombinant protein (LmSIR2) would affect T- and B-cell functions in a murine model. In vitro treatment of spleen cells from normal BALB/c mice with LmSIR2 showed increased expression of CD69 on B cells. This effect was not abolished by the addition of polymyxin B. Intravenous injection of LmSIR2 into BALB/c mice induced increased spleen B cell number by a factor of about ≈1·6, whereas no modification occurred at the level of CD4+ and CD8+ cells. Furthermore, intraperitoneal injection of LmSIR2 alone without adjuvant into BALB/c mice or nude mice triggered the production of elevated levels of LmSIR2-specific antibodies. The analysis of specific isotype profiles showed a predominance of immunoglobulin G1 (IgG1) and IgG2a antibody responses in BALB/c mice, and IgM in nude mice. Moreover, the anti-LmSIR2 mouse antibodies in the presence of complement induced the in vitro lysis of L. infantum amastigotes. In the absence of complement, the antibodies induced significant inhibition of amastigotes developpement inside macrophages. Together, the current study provides the first evidence that a Leishmania protein belonging to the SIR2 family may play a role in the regulation of immune response through its capacity to trigger B-cell effector function.","publication_date":{"day":null,"month":null,"year":2006,"errors":{}},"publication_name":"Immunology"},"translated_abstract":"In previous studies, we identified a gene product belonging to the silent information regulatory 2 protein (SIR2) family. This protein is expressed by all Leishmania species so far examined (L. major, L. infantum, L. amazonensis, L. mexicana) and found to be crucial for parasite survival and virulence. In the present study, we investigated whether a Leishmania SIR2 recombinant protein (LmSIR2) would affect T- and B-cell functions in a murine model. In vitro treatment of spleen cells from normal BALB/c mice with LmSIR2 showed increased expression of CD69 on B cells. This effect was not abolished by the addition of polymyxin B. Intravenous injection of LmSIR2 into BALB/c mice induced increased spleen B cell number by a factor of about ≈1·6, whereas no modification occurred at the level of CD4+ and CD8+ cells. Furthermore, intraperitoneal injection of LmSIR2 alone without adjuvant into BALB/c mice or nude mice triggered the production of elevated levels of LmSIR2-specific antibodies. The analysis of specific isotype profiles showed a predominance of immunoglobulin G1 (IgG1) and IgG2a antibody responses in BALB/c mice, and IgM in nude mice. Moreover, the anti-LmSIR2 mouse antibodies in the presence of complement induced the in vitro lysis of L. infantum amastigotes. In the absence of complement, the antibodies induced significant inhibition of amastigotes developpement inside macrophages. Together, the current study provides the first evidence that a Leishmania protein belonging to the SIR2 family may play a role in the regulation of immune response through its capacity to trigger B-cell effector function.","internal_url":"https://www.academia.edu/7143047/Leishmania_cytosolic_silent_information_regulatory_protein_2_deacetylase_induces_murine_B_cell_differentiation_and_in_vivo_production_of_specific_antibodies","translated_internal_url":"","created_at":"2014-05-24T01:01:51.146-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583901,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583901/thumbnails/1.jpg","file_name":"Leishmania_cytosolic_silent_information_20160905-30311-wsiq48.pdf","download_url":"https://www.academia.edu/attachments/48583901/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Leishmania_cytosolic_silent_information.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583901/Leishmania_cytosolic_silent_information_20160905-30311-wsiq48-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DLeishmania_cytosolic_silent_information.pdf\u0026Expires=1736775918\u0026Signature=EBm~FMwsIEHkOsUJ30pdRH9mIHJjKBhER5MwE--c26bphdihcDeWYu0wyrGoilqI6HcMn1NKQJ0At~ePuVlwt4w6vlxEpeshiar5RlTdJqU7UE~AGsCNV1ZAEOPZsyqporQP3zKlVRDVUMWvoPM2sXdZUFeLN~s1BC~7OqF8x-WPrs1l-Dkh1Dt-53aV9RYq4eKJv-ClwrHkFKyQMxWGC~LyBh4hle-65UMzSPsqMvUpcnsfd4I6FUxmM3m1BAIzEQGaiiupDV4UIPzkpk2WuzxHtrvHVYyWMWEqfHMb8OO0ywDFSQ8GGOKWLGTyJRXtCcTEC5udqTwOYCrAGy5-Iw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Leishmania_cytosolic_silent_information_regulatory_protein_2_deacetylase_induces_murine_B_cell_differentiation_and_in_vivo_production_of_specific_antibodies","translated_slug":"","page_count":12,"language":"en","content_type":"Work","summary":"In previous studies, we identified a gene product belonging to the silent information regulatory 2 protein (SIR2) family. This protein is expressed by all Leishmania species so far examined (L. major, L. infantum, L. amazonensis, L. mexicana) and found to be crucial for parasite survival and virulence. In the present study, we investigated whether a Leishmania SIR2 recombinant protein (LmSIR2) would affect T- and B-cell functions in a murine model. In vitro treatment of spleen cells from normal BALB/c mice with LmSIR2 showed increased expression of CD69 on B cells. This effect was not abolished by the addition of polymyxin B. Intravenous injection of LmSIR2 into BALB/c mice induced increased spleen B cell number by a factor of about ≈1·6, whereas no modification occurred at the level of CD4+ and CD8+ cells. Furthermore, intraperitoneal injection of LmSIR2 alone without adjuvant into BALB/c mice or nude mice triggered the production of elevated levels of LmSIR2-specific antibodies. The analysis of specific isotype profiles showed a predominance of immunoglobulin G1 (IgG1) and IgG2a antibody responses in BALB/c mice, and IgM in nude mice. Moreover, the anti-LmSIR2 mouse antibodies in the presence of complement induced the in vitro lysis of L. infantum amastigotes. In the absence of complement, the antibodies induced significant inhibition of amastigotes developpement inside macrophages. Together, the current study provides the first evidence that a Leishmania protein belonging to the SIR2 family may play a role in the regulation of immune response through its capacity to trigger B-cell effector function.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583901,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583901/thumbnails/1.jpg","file_name":"Leishmania_cytosolic_silent_information_20160905-30311-wsiq48.pdf","download_url":"https://www.academia.edu/attachments/48583901/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Leishmania_cytosolic_silent_information.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583901/Leishmania_cytosolic_silent_information_20160905-30311-wsiq48-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DLeishmania_cytosolic_silent_information.pdf\u0026Expires=1736775918\u0026Signature=EBm~FMwsIEHkOsUJ30pdRH9mIHJjKBhER5MwE--c26bphdihcDeWYu0wyrGoilqI6HcMn1NKQJ0At~ePuVlwt4w6vlxEpeshiar5RlTdJqU7UE~AGsCNV1ZAEOPZsyqporQP3zKlVRDVUMWvoPM2sXdZUFeLN~s1BC~7OqF8x-WPrs1l-Dkh1Dt-53aV9RYq4eKJv-ClwrHkFKyQMxWGC~LyBh4hle-65UMzSPsqMvUpcnsfd4I6FUxmM3m1BAIzEQGaiiupDV4UIPzkpk2WuzxHtrvHVYyWMWEqfHMb8OO0ywDFSQ8GGOKWLGTyJRXtCcTEC5udqTwOYCrAGy5-Iw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":1290,"name":"Immunology","url":"https://www.academia.edu/Documents/in/Immunology"},{"id":17491,"name":"Macrophages","url":"https://www.academia.edu/Documents/in/Macrophages"},{"id":49018,"name":"Spleen","url":"https://www.academia.edu/Documents/in/Spleen"},{"id":60436,"name":"Cell Differentiation","url":"https://www.academia.edu/Documents/in/Cell_Differentiation"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":208178,"name":"Sirtuins","url":"https://www.academia.edu/Documents/in/Sirtuins"},{"id":678853,"name":"B Lymphocytes","url":"https://www.academia.edu/Documents/in/B_Lymphocytes"},{"id":744838,"name":"Protozoan Proteins","url":"https://www.academia.edu/Documents/in/Protozoan_Proteins"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation"},{"id":789996,"name":"Leishmania infantum","url":"https://www.academia.edu/Documents/in/Leishmania_infantum"},{"id":990417,"name":"Recombinant Proteins","url":"https://www.academia.edu/Documents/in/Recombinant_Proteins"},{"id":1272906,"name":"Enzyme Linked Immunosorbent Assay","url":"https://www.academia.edu/Documents/in/Enzyme_Linked_Immunosorbent_Assay"},{"id":1716403,"name":"immunoglobulin G","url":"https://www.academia.edu/Documents/in/immunoglobulin_G"}],"urls":[{"id":2945790,"url":"http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2567.2006.02468.x"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143046"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143046/Immunological_alterations_induced_by_polyamine_derivatives_on_murine_splenocytes_and_human_mononuclear_cells"><img alt="Research paper thumbnail of Immunological alterations induced by polyamine derivatives on murine splenocytes and human mononuclear cells" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143046/Immunological_alterations_induced_by_polyamine_derivatives_on_murine_splenocytes_and_human_mononuclear_cells">Immunological alterations induced by polyamine derivatives on murine splenocytes and human mononuclear cells</a></div><div class="wp-workCard_item"><span>International Immunopharmacology</span><span>, 2004</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Three polyamine derivatives assigned as bis-naphthalimidopropyl putrescine (BNIPPut), spermidine ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Three polyamine derivatives assigned as bis-naphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd) and spermine (BNIPSpm) were studied to determine their effects on the proliferation of murine splenocytes and human peripheral blood mononuclear cells (PBMC) induced by the mitogens, Con A, LPS and PHA. All compounds showed a dose dependent inhibitory effect on mouse and human T cell proliferation induced by the mitogens, with BNIPPut exhibiting the most potent antiproliferative activity, followed by BNIPSpd and by BNIPSpm, respectively (Put &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Spd &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Spm), when considering human T cells. This suppressive activity also affects the capacity of mouse spleen cells to produce Th1 cytokines, namely IL-2 and INF-gamma after in vitro stimulation with Con A. The polyamine-induced inhibition also occurred in the case of LPS-stimulated B cells with a marked decrease of CD69 expression by these cells. Furthermore, the ability for these polyamine derivatives to induce apoptosis on Con A-stimulated splenocytes could be related to their antiproliferative activity.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143046"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143046"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143046; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143046]").text(description); $(".js-view-count[data-work-id=7143046]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143046; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143046']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143046, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=7143046]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143046,"title":"Immunological alterations induced by polyamine derivatives on murine splenocytes and human mononuclear cells","translated_title":"","metadata":{"abstract":"Three polyamine derivatives assigned as bis-naphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd) and spermine (BNIPSpm) were studied to determine their effects on the proliferation of murine splenocytes and human peripheral blood mononuclear cells (PBMC) induced by the mitogens, Con A, LPS and PHA. All compounds showed a dose dependent inhibitory effect on mouse and human T cell proliferation induced by the mitogens, with BNIPPut exhibiting the most potent antiproliferative activity, followed by BNIPSpd and by BNIPSpm, respectively (Put \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Spd \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Spm), when considering human T cells. This suppressive activity also affects the capacity of mouse spleen cells to produce Th1 cytokines, namely IL-2 and INF-gamma after in vitro stimulation with Con A. The polyamine-induced inhibition also occurred in the case of LPS-stimulated B cells with a marked decrease of CD69 expression by these cells. Furthermore, the ability for these polyamine derivatives to induce apoptosis on Con A-stimulated splenocytes could be related to their antiproliferative activity.","publication_date":{"day":null,"month":null,"year":2004,"errors":{}},"publication_name":"International Immunopharmacology"},"translated_abstract":"Three polyamine derivatives assigned as bis-naphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd) and spermine (BNIPSpm) were studied to determine their effects on the proliferation of murine splenocytes and human peripheral blood mononuclear cells (PBMC) induced by the mitogens, Con A, LPS and PHA. All compounds showed a dose dependent inhibitory effect on mouse and human T cell proliferation induced by the mitogens, with BNIPPut exhibiting the most potent antiproliferative activity, followed by BNIPSpd and by BNIPSpm, respectively (Put \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Spd \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Spm), when considering human T cells. This suppressive activity also affects the capacity of mouse spleen cells to produce Th1 cytokines, namely IL-2 and INF-gamma after in vitro stimulation with Con A. The polyamine-induced inhibition also occurred in the case of LPS-stimulated B cells with a marked decrease of CD69 expression by these cells. Furthermore, the ability for these polyamine derivatives to induce apoptosis on Con A-stimulated splenocytes could be related to their antiproliferative activity.","internal_url":"https://www.academia.edu/7143046/Immunological_alterations_induced_by_polyamine_derivatives_on_murine_splenocytes_and_human_mononuclear_cells","translated_internal_url":"","created_at":"2014-05-24T01:01:50.838-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Immunological_alterations_induced_by_polyamine_derivatives_on_murine_splenocytes_and_human_mononuclear_cells","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":"Three polyamine derivatives assigned as bis-naphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd) and spermine (BNIPSpm) were studied to determine their effects on the proliferation of murine splenocytes and human peripheral blood mononuclear cells (PBMC) induced by the mitogens, Con A, LPS and PHA. All compounds showed a dose dependent inhibitory effect on mouse and human T cell proliferation induced by the mitogens, with BNIPPut exhibiting the most potent antiproliferative activity, followed by BNIPSpd and by BNIPSpm, respectively (Put \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Spd \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Spm), when considering human T cells. This suppressive activity also affects the capacity of mouse spleen cells to produce Th1 cytokines, namely IL-2 and INF-gamma after in vitro stimulation with Con A. The polyamine-induced inhibition also occurred in the case of LPS-stimulated B cells with a marked decrease of CD69 expression by these cells. Furthermore, the ability for these polyamine derivatives to induce apoptosis on Con A-stimulated splenocytes could be related to their antiproliferative activity.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[],"research_interests":[{"id":6599,"name":"Flow Cytometry","url":"https://www.academia.edu/Documents/in/Flow_Cytometry"},{"id":9111,"name":"Cytokines","url":"https://www.academia.edu/Documents/in/Cytokines"},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis"},{"id":26699,"name":"Immunopharmacology","url":"https://www.academia.edu/Documents/in/Immunopharmacology"},{"id":49018,"name":"Spleen","url":"https://www.academia.edu/Documents/in/Spleen"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":195950,"name":"Quinolones","url":"https://www.academia.edu/Documents/in/Quinolones"},{"id":413195,"name":"Time Factors","url":"https://www.academia.edu/Documents/in/Time_Factors"},{"id":421782,"name":"Spermidine","url":"https://www.academia.edu/Documents/in/Spermidine"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation"},{"id":1272906,"name":"Enzyme Linked Immunosorbent Assay","url":"https://www.academia.edu/Documents/in/Enzyme_Linked_Immunosorbent_Assay"}],"urls":[{"id":2945789,"url":"http://www.sciencedirect.com/science/article/pii/S1567576904000608"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143044"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143044/The_Leishmania_infantum_cytosolic_SIR2_related_protein_1_LiSIR2RP1_is_an_NAD_dependent_deacetylase_and_ADP_ribosyltransferase"><img alt="Research paper thumbnail of The Leishmania infantum cytosolic SIR2-related protein 1 (LiSIR2RP1) is an NAD+-dependent deacetylase and ADP-ribosyltransferase" class="work-thumbnail" src="https://attachments.academia-assets.com/48583934/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143044/The_Leishmania_infantum_cytosolic_SIR2_related_protein_1_LiSIR2RP1_is_an_NAD_dependent_deacetylase_and_ADP_ribosyltransferase">The Leishmania infantum cytosolic SIR2-related protein 1 (LiSIR2RP1) is an NAD+-dependent deacetylase and ADP-ribosyltransferase</a></div><div class="wp-workCard_item"><span>Biochemical Journal</span><span>, 2008</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Proteins of the SIR2 (Silent Information Regulator 2) family are characterized by a conserved cat...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Proteins of the SIR2 (Silent Information Regulator 2) family are characterized by a conserved catalytic domain that exerts unique NAD + -dependent deacetylase activity on histones and various other cellular substrates. Previous reports from us have identified a Leishmania infantum gene encoding a cytosolic protein termed LiSIR2RP1 (Leishmania infantum SIR2-related protein 1) that belongs to the SIR2 family. Targeted disruption of one LiSIR2RP1 gene allele led to decreased amastigote virulence, in vitro as well as in vivo. In the present study, attempts were made for the first time to explore and characterize the enzymatic functions of LiSIR2RP1. The LiSIR2RP1 exhibited robust NAD + -dependent deacetylase and ADP-ribosyltransferase activities. Moreover, LiSIR2RP1 is capable of deacetylating tubulin, either in dimers or, when present, in taxol-stabilized microtubules or in promastigote and amastigote extracts. Furthermore, the immunostaining of parasites revealed a partial co-localization of α-tubulin and LiSIR2RP1 with punctate labelling, seen on the periphery of both promastigote and amastigote stages. Isolated parasite cyto-skeleton reacted with antibodies showed that part of LiSIR2RP1 is associated to the cytoskeleton network of both promastigote and amastigote forms. Moreover, the Western blot analysis of the soluble and insoluble fractions of the detergent of promastigote and amastigote forms revealed the presence of α-tubulin in the insoluble fraction, and the LiSIR2RP1 distributed in both soluble and insoluble fractions of promastigotes as well as amastigotes. Collectively, the results of the present study demonstrate that LiSIR2RP1 is an NAD + -dependent deacetylase that also exerts an ADP-ribosyltransferase activity. The fact that tubulin could be among the targets of LiSIR2RP1 may have significant implications during the remodelling of the morphology of the parasite and its interaction with the host cell.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="aa64525e1f18ae8c169db2dc9d2f33a4" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583934,"asset_id":7143044,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583934/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143044"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143044"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143044; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143044]").text(description); $(".js-view-count[data-work-id=7143044]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143044; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143044']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143044, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "aa64525e1f18ae8c169db2dc9d2f33a4" } } $('.js-work-strip[data-work-id=7143044]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143044,"title":"The Leishmania infantum cytosolic SIR2-related protein 1 (LiSIR2RP1) is an NAD+-dependent deacetylase and ADP-ribosyltransferase","translated_title":"","metadata":{"grobid_abstract":"Proteins of the SIR2 (Silent Information Regulator 2) family are characterized by a conserved catalytic domain that exerts unique NAD + -dependent deacetylase activity on histones and various other cellular substrates. Previous reports from us have identified a Leishmania infantum gene encoding a cytosolic protein termed LiSIR2RP1 (Leishmania infantum SIR2-related protein 1) that belongs to the SIR2 family. Targeted disruption of one LiSIR2RP1 gene allele led to decreased amastigote virulence, in vitro as well as in vivo. In the present study, attempts were made for the first time to explore and characterize the enzymatic functions of LiSIR2RP1. The LiSIR2RP1 exhibited robust NAD + -dependent deacetylase and ADP-ribosyltransferase activities. Moreover, LiSIR2RP1 is capable of deacetylating tubulin, either in dimers or, when present, in taxol-stabilized microtubules or in promastigote and amastigote extracts. Furthermore, the immunostaining of parasites revealed a partial co-localization of α-tubulin and LiSIR2RP1 with punctate labelling, seen on the periphery of both promastigote and amastigote stages. Isolated parasite cyto-skeleton reacted with antibodies showed that part of LiSIR2RP1 is associated to the cytoskeleton network of both promastigote and amastigote forms. Moreover, the Western blot analysis of the soluble and insoluble fractions of the detergent of promastigote and amastigote forms revealed the presence of α-tubulin in the insoluble fraction, and the LiSIR2RP1 distributed in both soluble and insoluble fractions of promastigotes as well as amastigotes. Collectively, the results of the present study demonstrate that LiSIR2RP1 is an NAD + -dependent deacetylase that also exerts an ADP-ribosyltransferase activity. The fact that tubulin could be among the targets of LiSIR2RP1 may have significant implications during the remodelling of the morphology of the parasite and its interaction with the host cell.","publication_date":{"day":null,"month":null,"year":2008,"errors":{}},"publication_name":"Biochemical Journal","grobid_abstract_attachment_id":48583934},"translated_abstract":null,"internal_url":"https://www.academia.edu/7143044/The_Leishmania_infantum_cytosolic_SIR2_related_protein_1_LiSIR2RP1_is_an_NAD_dependent_deacetylase_and_ADP_ribosyltransferase","translated_internal_url":"","created_at":"2014-05-24T01:01:50.535-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583934,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583934/thumbnails/1.jpg","file_name":"The_Leishmania_infantum_cytosolic_SIR2-r20160905-26881-qza57w.pdf","download_url":"https://www.academia.edu/attachments/48583934/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"The_Leishmania_infantum_cytosolic_SIR2_r.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583934/The_Leishmania_infantum_cytosolic_SIR2-r20160905-26881-qza57w-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DThe_Leishmania_infantum_cytosolic_SIR2_r.pdf\u0026Expires=1736775918\u0026Signature=MOoSzh-BjSfUTQsrcLIMc7Afzs7VQ8FFkPyBTJiJEwqJWBXuc-L624fJjv5KT5YSyW3RC-I65zz7ZGxr0qK~Bl64NMZSiS~i43RbdkpxLB0iCDKHkwJU2JMWxXh5ZOT~Mv1wD5Ck5QyEyUprK2x69ZyUAcInZ719E3nCT2NCx1vv8eoSRcelW0uofudqeCBLxYTE5agLNHTIyYMLuR-HkWrYjTovNkmVgKZLMaGwSJn34K7kHhzlAlwS3JBrKxfSU1Wpp8~MAbAtpp7MGAqO-MQrEOw8R6WpjdkZ7n0pqrNV0etytsTOAdKq13T7dz9OETTLXjSQ9Y-CSaPogbSfYQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"The_Leishmania_infantum_cytosolic_SIR2_related_protein_1_LiSIR2RP1_is_an_NAD_dependent_deacetylase_and_ADP_ribosyltransferase","translated_slug":"","page_count":10,"language":"en","content_type":"Work","summary":"Proteins of the SIR2 (Silent Information Regulator 2) family are characterized by a conserved catalytic domain that exerts unique NAD + -dependent deacetylase activity on histones and various other cellular substrates. Previous reports from us have identified a Leishmania infantum gene encoding a cytosolic protein termed LiSIR2RP1 (Leishmania infantum SIR2-related protein 1) that belongs to the SIR2 family. Targeted disruption of one LiSIR2RP1 gene allele led to decreased amastigote virulence, in vitro as well as in vivo. In the present study, attempts were made for the first time to explore and characterize the enzymatic functions of LiSIR2RP1. The LiSIR2RP1 exhibited robust NAD + -dependent deacetylase and ADP-ribosyltransferase activities. Moreover, LiSIR2RP1 is capable of deacetylating tubulin, either in dimers or, when present, in taxol-stabilized microtubules or in promastigote and amastigote extracts. Furthermore, the immunostaining of parasites revealed a partial co-localization of α-tubulin and LiSIR2RP1 with punctate labelling, seen on the periphery of both promastigote and amastigote stages. Isolated parasite cyto-skeleton reacted with antibodies showed that part of LiSIR2RP1 is associated to the cytoskeleton network of both promastigote and amastigote forms. Moreover, the Western blot analysis of the soluble and insoluble fractions of the detergent of promastigote and amastigote forms revealed the presence of α-tubulin in the insoluble fraction, and the LiSIR2RP1 distributed in both soluble and insoluble fractions of promastigotes as well as amastigotes. Collectively, the results of the present study demonstrate that LiSIR2RP1 is an NAD + -dependent deacetylase that also exerts an ADP-ribosyltransferase activity. The fact that tubulin could be among the targets of LiSIR2RP1 may have significant implications during the remodelling of the morphology of the parasite and its interaction with the host cell.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583934,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583934/thumbnails/1.jpg","file_name":"The_Leishmania_infantum_cytosolic_SIR2-r20160905-26881-qza57w.pdf","download_url":"https://www.academia.edu/attachments/48583934/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"The_Leishmania_infantum_cytosolic_SIR2_r.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583934/The_Leishmania_infantum_cytosolic_SIR2-r20160905-26881-qza57w-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DThe_Leishmania_infantum_cytosolic_SIR2_r.pdf\u0026Expires=1736775918\u0026Signature=MOoSzh-BjSfUTQsrcLIMc7Afzs7VQ8FFkPyBTJiJEwqJWBXuc-L624fJjv5KT5YSyW3RC-I65zz7ZGxr0qK~Bl64NMZSiS~i43RbdkpxLB0iCDKHkwJU2JMWxXh5ZOT~Mv1wD5Ck5QyEyUprK2x69ZyUAcInZ719E3nCT2NCx1vv8eoSRcelW0uofudqeCBLxYTE5agLNHTIyYMLuR-HkWrYjTovNkmVgKZLMaGwSJn34K7kHhzlAlwS3JBrKxfSU1Wpp8~MAbAtpp7MGAqO-MQrEOw8R6WpjdkZ7n0pqrNV0etytsTOAdKq13T7dz9OETTLXjSQ9Y-CSaPogbSfYQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":37508,"name":"Cytoskeleton","url":"https://www.academia.edu/Documents/in/Cytoskeleton"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":94271,"name":"Parasite","url":"https://www.academia.edu/Documents/in/Parasite"},{"id":176525,"name":"Biochemical","url":"https://www.academia.edu/Documents/in/Biochemical"},{"id":208178,"name":"Sirtuins","url":"https://www.academia.edu/Documents/in/Sirtuins"},{"id":260118,"name":"CHEMICAL SCIENCES","url":"https://www.academia.edu/Documents/in/CHEMICAL_SCIENCES"},{"id":533598,"name":"Tubulin","url":"https://www.academia.edu/Documents/in/Tubulin"},{"id":744838,"name":"Protozoan Proteins","url":"https://www.academia.edu/Documents/in/Protozoan_Proteins"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation"},{"id":789996,"name":"Leishmania infantum","url":"https://www.academia.edu/Documents/in/Leishmania_infantum"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival"}],"urls":[{"id":2945787,"url":"http://www.biochemj.org/bj/415/bj4150377.htm"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143043"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143043/Bisnaphthalimidopropyl_Derivatives_as_Inhibitors_of_Leishmania_SIR2_Related_Protein%C3%A2_1"><img alt="Research paper thumbnail of Bisnaphthalimidopropyl Derivatives as Inhibitors of Leishmania SIR2 Related Proteinâ 1" class="work-thumbnail" src="https://attachments.academia-assets.com/48583911/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143043/Bisnaphthalimidopropyl_Derivatives_as_Inhibitors_of_Leishmania_SIR2_Related_Protein%C3%A2_1">Bisnaphthalimidopropyl Derivatives as Inhibitors of Leishmania SIR2 Related Proteinâ 1</a></div><div class="wp-workCard_item"><span>Chemmedchem</span><span>, 2010</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The NAD+-dependent deacetylases, namely sirtuins, are involved in the regulation of a variety of ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The NAD+-dependent deacetylases, namely sirtuins, are involved in the regulation of a variety of biological processes such as gene silencing, DNA repair, longevity, metabolism, apoptosis, and development. An enzyme from the parasite Leishmania infantum that belongs to this family, LiSIR2RP1, is a NAD+-dependent tubulin deacetylase and an ADP-ribosyltransferase. This enzyme's involvement in L. infantum virulence and survival underscores its potential as a drug target. Our search for selective inhibitors of LiSIR2RP1 has led, for the first time, to the identification of the antiparasitic and anticancer bisnaphthalimidopropyl (BNIP) alkyl di- and triamines (IC50 values in the single-digit micromolar range for the most potent compounds). Structure–activity studies were conducted with 12 BNIP derivatives that differ in the length of the central alkyl chain, which links the two naphthalimidopropyl moieties. The most active and selective compound is the BNIP diaminononane (BNIPDanon), with IC50 values of 5.7 and 97.4 μM against the parasite and human forms (SIRT1) of the enzyme, respectively. Furthermore, this compound is an NAD+-competitive inhibitor that interacts differently with the parasite and human enzymes, as determined by docking analysis, which might explain its selectivity toward the parasitic enzyme.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="c0346087a5eb129102a51d1f7fa597d2" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583911,"asset_id":7143043,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583911/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143043"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143043"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143043; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143043]").text(description); $(".js-view-count[data-work-id=7143043]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143043; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143043']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143043, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "c0346087a5eb129102a51d1f7fa597d2" } } $('.js-work-strip[data-work-id=7143043]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143043,"title":"Bisnaphthalimidopropyl Derivatives as Inhibitors of Leishmania SIR2 Related Proteinâ 1","translated_title":"","metadata":{"abstract":"The NAD+-dependent deacetylases, namely sirtuins, are involved in the regulation of a variety of biological processes such as gene silencing, DNA repair, longevity, metabolism, apoptosis, and development. An enzyme from the parasite Leishmania infantum that belongs to this family, LiSIR2RP1, is a NAD+-dependent tubulin deacetylase and an ADP-ribosyltransferase. This enzyme's involvement in L. infantum virulence and survival underscores its potential as a drug target. Our search for selective inhibitors of LiSIR2RP1 has led, for the first time, to the identification of the antiparasitic and anticancer bisnaphthalimidopropyl (BNIP) alkyl di- and triamines (IC50 values in the single-digit micromolar range for the most potent compounds). Structure–activity studies were conducted with 12 BNIP derivatives that differ in the length of the central alkyl chain, which links the two naphthalimidopropyl moieties. The most active and selective compound is the BNIP diaminononane (BNIPDanon), with IC50 values of 5.7 and 97.4 μM against the parasite and human forms (SIRT1) of the enzyme, respectively. Furthermore, this compound is an NAD+-competitive inhibitor that interacts differently with the parasite and human enzymes, as determined by docking analysis, which might explain its selectivity toward the parasitic enzyme.","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"Chemmedchem"},"translated_abstract":"The NAD+-dependent deacetylases, namely sirtuins, are involved in the regulation of a variety of biological processes such as gene silencing, DNA repair, longevity, metabolism, apoptosis, and development. An enzyme from the parasite Leishmania infantum that belongs to this family, LiSIR2RP1, is a NAD+-dependent tubulin deacetylase and an ADP-ribosyltransferase. This enzyme's involvement in L. infantum virulence and survival underscores its potential as a drug target. Our search for selective inhibitors of LiSIR2RP1 has led, for the first time, to the identification of the antiparasitic and anticancer bisnaphthalimidopropyl (BNIP) alkyl di- and triamines (IC50 values in the single-digit micromolar range for the most potent compounds). Structure–activity studies were conducted with 12 BNIP derivatives that differ in the length of the central alkyl chain, which links the two naphthalimidopropyl moieties. The most active and selective compound is the BNIP diaminononane (BNIPDanon), with IC50 values of 5.7 and 97.4 μM against the parasite and human forms (SIRT1) of the enzyme, respectively. Furthermore, this compound is an NAD+-competitive inhibitor that interacts differently with the parasite and human enzymes, as determined by docking analysis, which might explain its selectivity toward the parasitic enzyme.","internal_url":"https://www.academia.edu/7143043/Bisnaphthalimidopropyl_Derivatives_as_Inhibitors_of_Leishmania_SIR2_Related_Protein%C3%A2_1","translated_internal_url":"","created_at":"2014-05-24T01:01:50.146-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583911,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583911/thumbnails/1.jpg","file_name":"Bisnaphthalimidopropyl_derivatives_as_in20160905-30903-yng3yz.pdf","download_url":"https://www.academia.edu/attachments/48583911/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Bisnaphthalimidopropyl_Derivatives_as_In.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583911/Bisnaphthalimidopropyl_derivatives_as_in20160905-30903-yng3yz-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DBisnaphthalimidopropyl_Derivatives_as_In.pdf\u0026Expires=1736775918\u0026Signature=X~erieiHVeEXtmLeepbMtL96rJC8LLDTfKDlxZILt9QTJ4ZMnplKtxLAYayzdZwjc~cWE~ZXTbF4glrDqlQpeVb9ICCgz9ej1VgVeDwnn~dZGRavkIPWfBYqoTeMejBOaCxtArhj4Alk~wQqDCBMeh~aytITULWF5iOPGDHcQcPszZlpZOcz992EVh7l21rsuU6kQpVlzKjIptoS4DhIUG41f7hRqOvx49voPE7chVtOPkm-4PlbXzASB1TWsO9tFtunsWJu1A8YIVd4TAEv7rcZ~Zz-VUO7rsDcTpNJZ4HLCbrKtd840LV2kYHiRIFawdAzNebASZ9UFwNxiRAoFg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Bisnaphthalimidopropyl_Derivatives_as_Inhibitors_of_Leishmania_SIR2_Related_Proteinâ_1","translated_slug":"","page_count":8,"language":"en","content_type":"Work","summary":"The NAD+-dependent deacetylases, namely sirtuins, are involved in the regulation of a variety of biological processes such as gene silencing, DNA repair, longevity, metabolism, apoptosis, and development. An enzyme from the parasite Leishmania infantum that belongs to this family, LiSIR2RP1, is a NAD+-dependent tubulin deacetylase and an ADP-ribosyltransferase. This enzyme's involvement in L. infantum virulence and survival underscores its potential as a drug target. Our search for selective inhibitors of LiSIR2RP1 has led, for the first time, to the identification of the antiparasitic and anticancer bisnaphthalimidopropyl (BNIP) alkyl di- and triamines (IC50 values in the single-digit micromolar range for the most potent compounds). Structure–activity studies were conducted with 12 BNIP derivatives that differ in the length of the central alkyl chain, which links the two naphthalimidopropyl moieties. The most active and selective compound is the BNIP diaminononane (BNIPDanon), with IC50 values of 5.7 and 97.4 μM against the parasite and human forms (SIRT1) of the enzyme, respectively. Furthermore, this compound is an NAD+-competitive inhibitor that interacts differently with the parasite and human enzymes, as determined by docking analysis, which might explain its selectivity toward the parasitic enzyme.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583911,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583911/thumbnails/1.jpg","file_name":"Bisnaphthalimidopropyl_derivatives_as_in20160905-30903-yng3yz.pdf","download_url":"https://www.academia.edu/attachments/48583911/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Bisnaphthalimidopropyl_Derivatives_as_In.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583911/Bisnaphthalimidopropyl_derivatives_as_in20160905-30903-yng3yz-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DBisnaphthalimidopropyl_Derivatives_as_In.pdf\u0026Expires=1736775918\u0026Signature=X~erieiHVeEXtmLeepbMtL96rJC8LLDTfKDlxZILt9QTJ4ZMnplKtxLAYayzdZwjc~cWE~ZXTbF4glrDqlQpeVb9ICCgz9ej1VgVeDwnn~dZGRavkIPWfBYqoTeMejBOaCxtArhj4Alk~wQqDCBMeh~aytITULWF5iOPGDHcQcPszZlpZOcz992EVh7l21rsuU6kQpVlzKjIptoS4DhIUG41f7hRqOvx49voPE7chVtOPkm-4PlbXzASB1TWsO9tFtunsWJu1A8YIVd4TAEv7rcZ~Zz-VUO7rsDcTpNJZ4HLCbrKtd840LV2kYHiRIFawdAzNebASZ9UFwNxiRAoFg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":531,"name":"Organic Chemistry","url":"https://www.academia.edu/Documents/in/Organic_Chemistry"},{"id":4987,"name":"Kinetics","url":"https://www.academia.edu/Documents/in/Kinetics"},{"id":12981,"name":"Enzyme Inhibitors","url":"https://www.academia.edu/Documents/in/Enzyme_Inhibitors"},{"id":69542,"name":"Computer Simulation","url":"https://www.academia.edu/Documents/in/Computer_Simulation"},{"id":147032,"name":"Naphthalimides","url":"https://www.academia.edu/Documents/in/Naphthalimides"},{"id":208178,"name":"Sirtuins","url":"https://www.academia.edu/Documents/in/Sirtuins"},{"id":213876,"name":"Docking","url":"https://www.academia.edu/Documents/in/Docking"},{"id":789996,"name":"Leishmania infantum","url":"https://www.academia.edu/Documents/in/Leishmania_infantum"},{"id":967839,"name":"Structure activity Relationship","url":"https://www.academia.edu/Documents/in/Structure_activity_Relationship"},{"id":1179557,"name":"Sirtuin","url":"https://www.academia.edu/Documents/in/Sirtuin"}],"urls":[{"id":2945786,"url":"http://doi.wiley.com/10.1002/cmdc.200900367"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143042"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143042/Antibodies_against_a_Leishmania_infantum_peroxiredoxin_as_a_possible_marker_for_diagnosis_of_visceral_leishmaniasis_and_for_monitoring_the_efficacy_of_treatment"><img alt="Research paper thumbnail of Antibodies against a Leishmania infantum peroxiredoxin as a possible marker for diagnosis of visceral leishmaniasis and for monitoring the efficacy of treatment" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143042/Antibodies_against_a_Leishmania_infantum_peroxiredoxin_as_a_possible_marker_for_diagnosis_of_visceral_leishmaniasis_and_for_monitoring_the_efficacy_of_treatment">Antibodies against a Leishmania infantum peroxiredoxin as a possible marker for diagnosis of visceral leishmaniasis and for monitoring the efficacy of treatment</a></div><div class="wp-workCard_item"><span>Immunology Letters</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Diagnosis of leishmaniasis is frequently based on serological methods, such as direct agglutinati...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Diagnosis of leishmaniasis is frequently based on serological methods, such as direct agglutination, immunofluorescence tests and ELISA assays with Leishmania total extracts, as antigen, however due to highly inconclusive results, more reliable tests are needed. In the present study, the prevalence of antibodies to a number of recombinant proteins (LmSIR2, LmS3a, LimTXNPx, LicTXNPx and LiTXN1) highly conserved among Leishmania species, were evaluated by ELISA in Leishmania infantum infected children from an endemic area of Portugal. We found that sera from children patients had antibodies against the different recombinant proteins, LicTXNPx presented the highest immuno-reactivity compared to the other and the most often recognized in the case of acute visceral leishmaniasis (VL). Moreover, in children treated with meglumine antimoniate or amphotericin B, antibodies against some of the recombinant proteins declined, whereas conventional serology using crude extracts showed little or no difference between the pre- and post-treatment values. The highest reduction was observed in the case of antibodies against the LicTXNPx protein. These results suggest that the antibodies against LicTXNPx might be a useful constituent of a defined serological test for the diagnosis and the monitoring of the therapeutic response in VL. The monitoring and follow-up in a large-scale field trials of such marker in areas where leishmaniasis is endemic will lend support to this.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143042"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143042"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143042; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143042]").text(description); $(".js-view-count[data-work-id=7143042]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143042; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143042']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143042, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=7143042]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143042,"title":"Antibodies against a Leishmania infantum peroxiredoxin as a possible marker for diagnosis of visceral leishmaniasis and for monitoring the efficacy of treatment","translated_title":"","metadata":{"abstract":"Diagnosis of leishmaniasis is frequently based on serological methods, such as direct agglutination, immunofluorescence tests and ELISA assays with Leishmania total extracts, as antigen, however due to highly inconclusive results, more reliable tests are needed. In the present study, the prevalence of antibodies to a number of recombinant proteins (LmSIR2, LmS3a, LimTXNPx, LicTXNPx and LiTXN1) highly conserved among Leishmania species, were evaluated by ELISA in Leishmania infantum infected children from an endemic area of Portugal. We found that sera from children patients had antibodies against the different recombinant proteins, LicTXNPx presented the highest immuno-reactivity compared to the other and the most often recognized in the case of acute visceral leishmaniasis (VL). Moreover, in children treated with meglumine antimoniate or amphotericin B, antibodies against some of the recombinant proteins declined, whereas conventional serology using crude extracts showed little or no difference between the pre- and post-treatment values. The highest reduction was observed in the case of antibodies against the LicTXNPx protein. These results suggest that the antibodies against LicTXNPx might be a useful constituent of a defined serological test for the diagnosis and the monitoring of the therapeutic response in VL. The monitoring and follow-up in a large-scale field trials of such marker in areas where leishmaniasis is endemic will lend support to this.","publication_date":{"day":null,"month":null,"year":2005,"errors":{}},"publication_name":"Immunology Letters"},"translated_abstract":"Diagnosis of leishmaniasis is frequently based on serological methods, such as direct agglutination, immunofluorescence tests and ELISA assays with Leishmania total extracts, as antigen, however due to highly inconclusive results, more reliable tests are needed. In the present study, the prevalence of antibodies to a number of recombinant proteins (LmSIR2, LmS3a, LimTXNPx, LicTXNPx and LiTXN1) highly conserved among Leishmania species, were evaluated by ELISA in Leishmania infantum infected children from an endemic area of Portugal. We found that sera from children patients had antibodies against the different recombinant proteins, LicTXNPx presented the highest immuno-reactivity compared to the other and the most often recognized in the case of acute visceral leishmaniasis (VL). Moreover, in children treated with meglumine antimoniate or amphotericin B, antibodies against some of the recombinant proteins declined, whereas conventional serology using crude extracts showed little or no difference between the pre- and post-treatment values. The highest reduction was observed in the case of antibodies against the LicTXNPx protein. These results suggest that the antibodies against LicTXNPx might be a useful constituent of a defined serological test for the diagnosis and the monitoring of the therapeutic response in VL. The monitoring and follow-up in a large-scale field trials of such marker in areas where leishmaniasis is endemic will lend support to this.","internal_url":"https://www.academia.edu/7143042/Antibodies_against_a_Leishmania_infantum_peroxiredoxin_as_a_possible_marker_for_diagnosis_of_visceral_leishmaniasis_and_for_monitoring_the_efficacy_of_treatment","translated_internal_url":"","created_at":"2014-05-24T01:01:49.819-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Antibodies_against_a_Leishmania_infantum_peroxiredoxin_as_a_possible_marker_for_diagnosis_of_visceral_leishmaniasis_and_for_monitoring_the_efficacy_of_treatment","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":"Diagnosis of leishmaniasis is frequently based on serological methods, such as direct agglutination, immunofluorescence tests and ELISA assays with Leishmania total extracts, as antigen, however due to highly inconclusive results, more reliable tests are needed. In the present study, the prevalence of antibodies to a number of recombinant proteins (LmSIR2, LmS3a, LimTXNPx, LicTXNPx and LiTXN1) highly conserved among Leishmania species, were evaluated by ELISA in Leishmania infantum infected children from an endemic area of Portugal. We found that sera from children patients had antibodies against the different recombinant proteins, LicTXNPx presented the highest immuno-reactivity compared to the other and the most often recognized in the case of acute visceral leishmaniasis (VL). Moreover, in children treated with meglumine antimoniate or amphotericin B, antibodies against some of the recombinant proteins declined, whereas conventional serology using crude extracts showed little or no difference between the pre- and post-treatment values. The highest reduction was observed in the case of antibodies against the LicTXNPx protein. These results suggest that the antibodies against LicTXNPx might be a useful constituent of a defined serological test for the diagnosis and the monitoring of the therapeutic response in VL. The monitoring and follow-up in a large-scale field trials of such marker in areas where leishmaniasis is endemic will lend support to this.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[],"research_interests":[{"id":1290,"name":"Immunology","url":"https://www.academia.edu/Documents/in/Immunology"},{"id":64933,"name":"Child","url":"https://www.academia.edu/Documents/in/Child"},{"id":128004,"name":"Visceral Leishmaniasis","url":"https://www.academia.edu/Documents/in/Visceral_Leishmaniasis"},{"id":320165,"name":"Field Trial","url":"https://www.academia.edu/Documents/in/Field_Trial"},{"id":568482,"name":"Biological markers","url":"https://www.academia.edu/Documents/in/Biological_markers"},{"id":758278,"name":"Large Scale","url":"https://www.academia.edu/Documents/in/Large_Scale"},{"id":789996,"name":"Leishmania infantum","url":"https://www.academia.edu/Documents/in/Leishmania_infantum"},{"id":959510,"name":"Recombinant Protein","url":"https://www.academia.edu/Documents/in/Recombinant_Protein"},{"id":1716403,"name":"immunoglobulin G","url":"https://www.academia.edu/Documents/in/immunoglobulin_G"},{"id":2211535,"name":"Peroxiredoxins","url":"https://www.academia.edu/Documents/in/Peroxiredoxins"}],"urls":[{"id":2945785,"url":"http://www.sciencedirect.com/science/article/pii/S0165247805001057"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143041"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143041/Immune_Response_Regulation_by_Leishmania_Secreted_and_Nonsecreted_Antigens"><img alt="Research paper thumbnail of Immune Response Regulation by Leishmania Secreted and Nonsecreted Antigens" class="work-thumbnail" src="https://attachments.academia-assets.com/48583923/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143041/Immune_Response_Regulation_by_Leishmania_Secreted_and_Nonsecreted_Antigens">Immune Response Regulation by Leishmania Secreted and Nonsecreted Antigens</a></div><div class="wp-workCard_item"><span>Journal of Biomedicine and Biotechnology</span><span>, 2007</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Leishmania infection consists in two sequential events, the host cell colonization followed by th...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Leishmania infection consists in two sequential events, the host cell colonization followed by the proliferation/dissemination of the parasite. In this review, we discuss the importance of two distinct sets of molecules, the secreted and/or surface and the nonsecreted antigens. The importance of the immune response against secreted and surface antigens is noted in the establishment of the infection and we dissect the contribution of the nonsecreted antigens in the immunopathology associated with leishmaniasis, showing the importance of these panantigens during the course of the infection. As a further example of proteins belonging to these two different groups, we include several laboratorial observations on Leishmania Sir2 and LicTXNPx as excreted/secreted proteins and LmS3arp and LimTXNPx as nonsecreted/panantigens. The role of these two groups of antigens in the immune response observed during the infection is discussed.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="6491f53c5b831867ad14bab3bcdc3e23" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583923,"asset_id":7143041,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583923/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143041"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143041"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143041; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143041]").text(description); $(".js-view-count[data-work-id=7143041]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143041; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143041']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143041, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "6491f53c5b831867ad14bab3bcdc3e23" } } $('.js-work-strip[data-work-id=7143041]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143041,"title":"Immune Response Regulation by Leishmania Secreted and Nonsecreted Antigens","translated_title":"","metadata":{"grobid_abstract":"Leishmania infection consists in two sequential events, the host cell colonization followed by the proliferation/dissemination of the parasite. In this review, we discuss the importance of two distinct sets of molecules, the secreted and/or surface and the nonsecreted antigens. The importance of the immune response against secreted and surface antigens is noted in the establishment of the infection and we dissect the contribution of the nonsecreted antigens in the immunopathology associated with leishmaniasis, showing the importance of these panantigens during the course of the infection. As a further example of proteins belonging to these two different groups, we include several laboratorial observations on Leishmania Sir2 and LicTXNPx as excreted/secreted proteins and LmS3arp and LimTXNPx as nonsecreted/panantigens. The role of these two groups of antigens in the immune response observed during the infection is discussed.","publication_date":{"day":null,"month":null,"year":2007,"errors":{}},"publication_name":"Journal of Biomedicine and Biotechnology","grobid_abstract_attachment_id":48583923},"translated_abstract":null,"internal_url":"https://www.academia.edu/7143041/Immune_Response_Regulation_by_Leishmania_Secreted_and_Nonsecreted_Antigens","translated_internal_url":"","created_at":"2014-05-24T01:01:49.529-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583923,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583923/thumbnails/1.jpg","file_name":"Immune_response_regulation_by_leishmania20160905-28746-1zzr7w.pdf","download_url":"https://www.academia.edu/attachments/48583923/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Immune_Response_Regulation_by_Leishmania.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583923/Immune_response_regulation_by_leishmania20160905-28746-1zzr7w-libre.pdf?1473073947=\u0026response-content-disposition=attachment%3B+filename%3DImmune_Response_Regulation_by_Leishmania.pdf\u0026Expires=1736775918\u0026Signature=fba9JdVXMf9htOejxMQ~54YQ66VJpaiGyNVxjxuDwShnSS8ll2tQXcHz1QIEiD9oM5SqN5UIXYuURbYTnuNtVJapMtYoDOxu6HGWrIWvlz1UIj89E3YAqEMZyuOhgSs0S7Ox-2yGkaQbao9rfZ1vNrd9TYvpvjdag~siil~OxselhDJPMB3zf8fQ13BMMen5-gpOZQVoqKR-2JOpMNBlKqd~i05kSr8nwJV74TSIS0fvUR8ZU6NsXgUp~6qglt8O~sQhBawe2NB-9JF3duhX1i4~Rkfl1oBFPEMGHdCAQ4QWfHZ2jVoy9HMNvU-rxCa~wHjGExzYNj0Zzs0w-yvdrg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Immune_Response_Regulation_by_Leishmania_Secreted_and_Nonsecreted_Antigens","translated_slug":"","page_count":10,"language":"en","content_type":"Work","summary":"Leishmania infection consists in two sequential events, the host cell colonization followed by the proliferation/dissemination of the parasite. In this review, we discuss the importance of two distinct sets of molecules, the secreted and/or surface and the nonsecreted antigens. The importance of the immune response against secreted and surface antigens is noted in the establishment of the infection and we dissect the contribution of the nonsecreted antigens in the immunopathology associated with leishmaniasis, showing the importance of these panantigens during the course of the infection. As a further example of proteins belonging to these two different groups, we include several laboratorial observations on Leishmania Sir2 and LicTXNPx as excreted/secreted proteins and LmS3arp and LimTXNPx as nonsecreted/panantigens. The role of these two groups of antigens in the immune response observed during the infection is discussed.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583923,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583923/thumbnails/1.jpg","file_name":"Immune_response_regulation_by_leishmania20160905-28746-1zzr7w.pdf","download_url":"https://www.academia.edu/attachments/48583923/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Immune_Response_Regulation_by_Leishmania.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583923/Immune_response_regulation_by_leishmania20160905-28746-1zzr7w-libre.pdf?1473073947=\u0026response-content-disposition=attachment%3B+filename%3DImmune_Response_Regulation_by_Leishmania.pdf\u0026Expires=1736775918\u0026Signature=fba9JdVXMf9htOejxMQ~54YQ66VJpaiGyNVxjxuDwShnSS8ll2tQXcHz1QIEiD9oM5SqN5UIXYuURbYTnuNtVJapMtYoDOxu6HGWrIWvlz1UIj89E3YAqEMZyuOhgSs0S7Ox-2yGkaQbao9rfZ1vNrd9TYvpvjdag~siil~OxselhDJPMB3zf8fQ13BMMen5-gpOZQVoqKR-2JOpMNBlKqd~i05kSr8nwJV74TSIS0fvUR8ZU6NsXgUp~6qglt8O~sQhBawe2NB-9JF3duhX1i4~Rkfl1oBFPEMGHdCAQ4QWfHZ2jVoy9HMNvU-rxCa~wHjGExzYNj0Zzs0w-yvdrg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":923,"name":"Technology","url":"https://www.academia.edu/Documents/in/Technology"},{"id":1066,"name":"Biomedicine","url":"https://www.academia.edu/Documents/in/Biomedicine"},{"id":2702,"name":"Immune response","url":"https://www.academia.edu/Documents/in/Immune_response"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":222543,"name":"Biomed","url":"https://www.academia.edu/Documents/in/Biomed"}],"urls":[{"id":2945784,"url":"http://www.hindawi.com/journals/jbb/2007/085154.pdf"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143040"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143040/Activation_of_Phosphatidylinositol_3Kinase_Akt_and_Impairment_of_Nuclear_Factor_%CE%BAB"><img alt="Research paper thumbnail of Activation of Phosphatidylinositol 3Kinase/Akt and Impairment of Nuclear Factor-κB" class="work-thumbnail" src="https://attachments.academia-assets.com/48583913/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143040/Activation_of_Phosphatidylinositol_3Kinase_Akt_and_Impairment_of_Nuclear_Factor_%CE%BAB">Activation of Phosphatidylinositol 3Kinase/Akt and Impairment of Nuclear Factor-κB</a></div><div class="wp-workCard_item"><span>American Journal of Pathology</span><span>, 2010</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Supported by Fundaç ã o para a Ciê ncia e a Tecnologia (FCT) and Fundo Europeu de Desenvolvimento...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Supported by Fundaç ã o para a Ciê ncia e a Tecnologia (FCT) and Fundo Europeu de Desenvolvimento Regional (FEDER) Ciê ncia Bone marrow-dendritic cells (BMDCs) were derived as described previously. In brief, bone marrow from femurs and tibiae of 10-to 12-week-old BALB/c mice were flushed with RPMI 1640, using syringes and 25-gauge needles. The tissue was resuspended, and BMDCs were obtained by seeding 5 ϫ 10 6 bone marrow cells in 25 ml of RPMIc supplemented with 50 mol/L 2-mercaptoethanol (Sigma Chemical Co.) and 200 U/ml of granulocyte macrophage-colony-stimulating factor (GM-CSF) (PeproTech, Rocky Hill, NJ) (DC medium).</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="65762f2053d856e3ce9edf44d951b02e" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583913,"asset_id":7143040,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583913/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143040"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143040"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143040; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143040]").text(description); $(".js-view-count[data-work-id=7143040]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143040; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143040']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143040, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "65762f2053d856e3ce9edf44d951b02e" } } $('.js-work-strip[data-work-id=7143040]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143040,"title":"Activation of Phosphatidylinositol 3Kinase/Akt and Impairment of Nuclear Factor-κB","translated_title":"","metadata":{"grobid_abstract":"Supported by Fundaç ã o para a Ciê ncia e a Tecnologia (FCT) and Fundo Europeu de Desenvolvimento Regional (FEDER) Ciê ncia Bone marrow-dendritic cells (BMDCs) were derived as described previously. 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In brief, bone marrow from femurs and tibiae of 10-to 12-week-old BALB/c mice were flushed with RPMI 1640, using syringes and 25-gauge needles. 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nanoparticles" class="work-thumbnail" src="https://attachments.academia-assets.com/48583940/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143039/Immune_response_by_nasal_delivery_of_hepatitis_B_surface_antigen_and_codelivery_of_a_CpG_ODN_in_alginate_coated_chitosan_nanoparticles">Immune response by nasal delivery of hepatitis B surface antigen and codelivery of a CpG ODN in alginate coated chitosan nanoparticles</a></div><div class="wp-workCard_item"><span>European Journal of Pharmaceutics and Biopharmaceutics</span><span>, 2008</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Alginate coated chitosan nanoparticles were previously developed with the aim of protecting the a...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Alginate coated chitosan nanoparticles were previously developed with the aim of protecting the antigen, adsorbed on the surface of those chitosan nanoparticles, from enzymatic degradation at mucosal surfaces. In this work, this new delivery system was loaded with the recombinant hepatitis B surface antigen (HBsAg) and applied to mice by the intranasal route. Adjuvant effect of the delivery system was studied by measuring anti-HBsAg IgG in serum, anti-HBsAg sIgA in faeces extracts or nasal and vaginal secretions and interferon-c production in supernatants of the spleen cells. The mice were primed with 10 lg of the vaccine associated or not with nanoparticles and associated or not with 10 lg CpG oligodeoxynucleotide (ODN) followed by two sequential boosts at three week intervals. The association of HBsAg with the alginate coated chitosan nanoparticles, administered intranasally to the mice, gave rise to the humoral mucosal immune response. Humoral systemic immune response was not induced by the HBsAg loaded nanoparticles alone. The generation of Th1-biased antigen-specific systemic antibodies, however, was observed when HBsAg loaded nanoparticles were applied together with a second adjuvant, the immunopotentiator, CpG ODN. Moreover, all intranasally vaccinated groups showed higher interferon-c production when compared to naïve mice.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="f6ffc4d4ed4335092b349bd3b07b9333" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583940,"asset_id":7143039,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583940/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143039"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143039"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143039; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143039]").text(description); $(".js-view-count[data-work-id=7143039]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143039; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143039']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143039, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "f6ffc4d4ed4335092b349bd3b07b9333" } } $('.js-work-strip[data-work-id=7143039]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143039,"title":"Immune response by nasal delivery of hepatitis B surface antigen and codelivery of a CpG ODN in alginate coated chitosan nanoparticles","translated_title":"","metadata":{"ai_title_tag":"Nasal Delivery of HBsAg via Chitosan Nanoparticles and CpG ODN","grobid_abstract":"Alginate coated chitosan nanoparticles were previously developed with the aim of protecting the antigen, adsorbed on the surface of those chitosan nanoparticles, from enzymatic degradation at mucosal surfaces. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143038"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143038/Structure_Function_Analysis_of_Leishmania_Sirtuin_An_Ensemble_of_In_Silico_and_Biochemical_Studies"><img alt="Research paper thumbnail of Structure Function Analysis of Leishmania Sirtuin: An Ensemble of In Silico and Biochemical Studies" class="work-thumbnail" src="https://attachments.academia-assets.com/48583889/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143038/Structure_Function_Analysis_of_Leishmania_Sirtuin_An_Ensemble_of_In_Silico_and_Biochemical_Studies">Structure Function Analysis of Leishmania Sirtuin: An Ensemble of In Silico and Biochemical Studies</a></div><div class="wp-workCard_item"><span>Chemical Biology & Drug Design</span><span>, 2008</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Novel anti-leishmanial target LmSir2 has few subtle but prudent structural differences in ligand ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Novel anti-leishmanial target LmSir2 has few subtle but prudent structural differences in ligand binding and catalytic domain as compared to its human counterpart. In silico screening and validation followed by in vitro deacetylation and cell killing assays described herein give a proof of concept for development of strategies exploiting such minor differences for screening libraries of small molecules to identify selective inhibitors.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="8a75798a0c3d95fd671fdd321f19f7f7" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583889,"asset_id":7143038,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583889/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143038"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143038"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143038; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143038]").text(description); $(".js-view-count[data-work-id=7143038]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143038; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143038']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143038, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "8a75798a0c3d95fd671fdd321f19f7f7" } } $('.js-work-strip[data-work-id=7143038]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143038,"title":"Structure Function Analysis of Leishmania Sirtuin: An Ensemble of In Silico and Biochemical Studies","translated_title":"","metadata":{"abstract":"Novel anti-leishmanial target LmSir2 has few subtle but prudent structural differences in ligand binding and catalytic domain as compared to its human counterpart. In silico screening and validation followed by in vitro deacetylation and cell killing assays described herein give a proof of concept for development of strategies exploiting such minor differences for screening libraries of small molecules to identify selective inhibitors.","publication_date":{"day":null,"month":null,"year":2008,"errors":{}},"publication_name":"Chemical Biology \u0026 Drug Design"},"translated_abstract":"Novel anti-leishmanial target LmSir2 has few subtle but prudent structural differences in ligand binding and catalytic domain as compared to its human counterpart. In silico screening and validation followed by in vitro deacetylation and cell killing assays described herein give a proof of concept for development of strategies exploiting such minor differences for screening libraries of small molecules to identify selective inhibitors.","internal_url":"https://www.academia.edu/7143038/Structure_Function_Analysis_of_Leishmania_Sirtuin_An_Ensemble_of_In_Silico_and_Biochemical_Studies","translated_internal_url":"","created_at":"2014-05-24T01:01:48.711-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583889,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583889/thumbnails/1.jpg","file_name":"j.1747-0285.2008.00652.x20160905-19689-18cb7ja.pdf","download_url":"https://www.academia.edu/attachments/48583889/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Structure_Function_Analysis_of_Leishmani.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583889/j.1747-0285.2008.00652.x20160905-19689-18cb7ja-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DStructure_Function_Analysis_of_Leishmani.pdf\u0026Expires=1736775918\u0026Signature=DCJ-j6pfzC~tfoPt5z~IblfI1fO7l6tcbyl6SOwSVsUFbRDIqnWc9BDQtINRdZR2p3z9cChqQFf72UcQb~b6i22S7fPPa0Y4RQQDI5j3apORUXWU2K5E2fSKTYTlBSGq898k2EiNoxUK2o5b328JAtdZATn0TOdU0uLgn3faLXjov-chnmN0DZVpYc~B2RlVWhvrHkRsPMa12o7r7wGw3ZFfgCPqfx9yNu4PUTIK~l9QjYkdzgI2SQJUQIv2WlnXgbFEp3c~NtSxvEovUwaMyqkGtFGhu-1VrjXPg4FzETI7i19S4E-aPUNbFOKMVXY6q8pSfAx8INd72tgRTrXDOw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Structure_Function_Analysis_of_Leishmania_Sirtuin_An_Ensemble_of_In_Silico_and_Biochemical_Studies","translated_slug":"","page_count":6,"language":"en","content_type":"Work","summary":"Novel anti-leishmanial target LmSir2 has few subtle but prudent structural differences in ligand binding and catalytic domain as compared to its human counterpart. In silico screening and validation followed by in vitro deacetylation and cell killing assays described herein give a proof of concept for development of strategies exploiting such minor differences for screening libraries of small molecules to identify selective inhibitors.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583889,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583889/thumbnails/1.jpg","file_name":"j.1747-0285.2008.00652.x20160905-19689-18cb7ja.pdf","download_url":"https://www.academia.edu/attachments/48583889/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Structure_Function_Analysis_of_Leishmani.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583889/j.1747-0285.2008.00652.x20160905-19689-18cb7ja-libre.pdf?1473073945=\u0026response-content-disposition=attachment%3B+filename%3DStructure_Function_Analysis_of_Leishmani.pdf\u0026Expires=1736775918\u0026Signature=DCJ-j6pfzC~tfoPt5z~IblfI1fO7l6tcbyl6SOwSVsUFbRDIqnWc9BDQtINRdZR2p3z9cChqQFf72UcQb~b6i22S7fPPa0Y4RQQDI5j3apORUXWU2K5E2fSKTYTlBSGq898k2EiNoxUK2o5b328JAtdZATn0TOdU0uLgn3faLXjov-chnmN0DZVpYc~B2RlVWhvrHkRsPMa12o7r7wGw3ZFfgCPqfx9yNu4PUTIK~l9QjYkdzgI2SQJUQIv2WlnXgbFEp3c~NtSxvEovUwaMyqkGtFGhu-1VrjXPg4FzETI7i19S4E-aPUNbFOKMVXY6q8pSfAx8INd72tgRTrXDOw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":12981,"name":"Enzyme Inhibitors","url":"https://www.academia.edu/Documents/in/Enzyme_Inhibitors"},{"id":19849,"name":"Leishmania","url":"https://www.academia.edu/Documents/in/Leishmania"},{"id":21180,"name":"Chemical Biology","url":"https://www.academia.edu/Documents/in/Chemical_Biology"},{"id":112576,"name":"Cell Death","url":"https://www.academia.edu/Documents/in/Cell_Death"},{"id":157521,"name":"Quantitative Structure Activity Relationship","url":"https://www.academia.edu/Documents/in/Quantitative_Structure_Activity_Relationship"},{"id":208178,"name":"Sirtuins","url":"https://www.academia.edu/Documents/in/Sirtuins"},{"id":865697,"name":"In Silico","url":"https://www.academia.edu/Documents/in/In_Silico"},{"id":1011864,"name":"Structure Function","url":"https://www.academia.edu/Documents/in/Structure_Function"},{"id":1681026,"name":"Biochemistry and cell biology","url":"https://www.academia.edu/Documents/in/Biochemistry_and_cell_biology"}],"urls":[{"id":2945781,"url":"http://www.blackwell-synergy.com/doi/abs/10.1111/j.1747-0285.2008.00652.x"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143037"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143037/Effect_of_nonsteroidal_anti_inflammatory_drugs_on_the_cellular_membrane_fluidity"><img alt="Research paper thumbnail of Effect of nonsteroidal anti‐inflammatory drugs on the cellular membrane fluidity" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143037/Effect_of_nonsteroidal_anti_inflammatory_drugs_on_the_cellular_membrane_fluidity">Effect of nonsteroidal anti‐inflammatory drugs on the cellular membrane fluidity</a></div><div class="wp-workCard_item"><span>Journal of Pharmaceutical Sciences</span><span>, 2008</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">In this work, fluorescence measurements were performed using the fluorescent probe 1,6-diphenyl-1...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">In this work, fluorescence measurements were performed using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) to evaluate the effects of the interaction of nonsteroidal anti-inflammatory drugs—NSAIDs (meloxicam, lornoxicam, and nimesulide) with several membrane systems (liposomes with and without cholesterol, mouse splenocytes, mouse macrophages cell line—J774, human leukemia monocyte cell line—THP-1, and human granulocytes and mononuclear cells). DPH fluorescence quenching studies revealed that the NSAIDs studied were able to efficiently quench the probe located in membrane hydrocarbon region. Fluorescence anisotropy measurements were also made to investigate the effects on membrane fluidity resulting from the interaction between the drugs and membrane systems. All the anti-inflammatory drugs studied show an increase in the membrane fluidity in a concentration dependent manner. Results obtained provide an insight into NSAIDs capacity to be inserted in lipid bilayers and alter the lipid dynamics. The induced changes in lipid dynamics may modulate the activity of inflammatory enzymes or may be related with deleterious topical action of NSAIDs on gastric phospholipid fluidity. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 3195–3206, 2008</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143037"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143037"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143037; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143037]").text(description); $(".js-view-count[data-work-id=7143037]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143037; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143037']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143037, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=7143037]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143037,"title":"Effect of nonsteroidal anti‐inflammatory drugs on the cellular membrane fluidity","translated_title":"","metadata":{"abstract":"In this work, fluorescence measurements were performed using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) to evaluate the effects of the interaction of nonsteroidal anti-inflammatory drugs—NSAIDs (meloxicam, lornoxicam, and nimesulide) with several membrane systems (liposomes with and without cholesterol, mouse splenocytes, mouse macrophages cell line—J774, human leukemia monocyte cell line—THP-1, and human granulocytes and mononuclear cells). DPH fluorescence quenching studies revealed that the NSAIDs studied were able to efficiently quench the probe located in membrane hydrocarbon region. Fluorescence anisotropy measurements were also made to investigate the effects on membrane fluidity resulting from the interaction between the drugs and membrane systems. All the anti-inflammatory drugs studied show an increase in the membrane fluidity in a concentration dependent manner. Results obtained provide an insight into NSAIDs capacity to be inserted in lipid bilayers and alter the lipid dynamics. The induced changes in lipid dynamics may modulate the activity of inflammatory enzymes or may be related with deleterious topical action of NSAIDs on gastric phospholipid fluidity. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 3195–3206, 2008","publication_date":{"day":null,"month":null,"year":2008,"errors":{}},"publication_name":"Journal of Pharmaceutical Sciences"},"translated_abstract":"In this work, fluorescence measurements were performed using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) to evaluate the effects of the interaction of nonsteroidal anti-inflammatory drugs—NSAIDs (meloxicam, lornoxicam, and nimesulide) with several membrane systems (liposomes with and without cholesterol, mouse splenocytes, mouse macrophages cell line—J774, human leukemia monocyte cell line—THP-1, and human granulocytes and mononuclear cells). DPH fluorescence quenching studies revealed that the NSAIDs studied were able to efficiently quench the probe located in membrane hydrocarbon region. Fluorescence anisotropy measurements were also made to investigate the effects on membrane fluidity resulting from the interaction between the drugs and membrane systems. All the anti-inflammatory drugs studied show an increase in the membrane fluidity in a concentration dependent manner. Results obtained provide an insight into NSAIDs capacity to be inserted in lipid bilayers and alter the lipid dynamics. The induced changes in lipid dynamics may modulate the activity of inflammatory enzymes or may be related with deleterious topical action of NSAIDs on gastric phospholipid fluidity. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 3195–3206, 2008","internal_url":"https://www.academia.edu/7143037/Effect_of_nonsteroidal_anti_inflammatory_drugs_on_the_cellular_membrane_fluidity","translated_internal_url":"","created_at":"2014-05-24T01:01:48.522-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Effect_of_nonsteroidal_anti_inflammatory_drugs_on_the_cellular_membrane_fluidity","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":"In this work, fluorescence measurements were performed using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) to evaluate the effects of the interaction of nonsteroidal anti-inflammatory drugs—NSAIDs (meloxicam, lornoxicam, and nimesulide) with several membrane systems (liposomes with and without cholesterol, mouse splenocytes, mouse macrophages cell line—J774, human leukemia monocyte cell line—THP-1, and human granulocytes and mononuclear cells). DPH fluorescence quenching studies revealed that the NSAIDs studied were able to efficiently quench the probe located in membrane hydrocarbon region. Fluorescence anisotropy measurements were also made to investigate the effects on membrane fluidity resulting from the interaction between the drugs and membrane systems. All the anti-inflammatory drugs studied show an increase in the membrane fluidity in a concentration dependent manner. Results obtained provide an insight into NSAIDs capacity to be inserted in lipid bilayers and alter the lipid dynamics. The induced changes in lipid dynamics may modulate the activity of inflammatory enzymes or may be related with deleterious topical action of NSAIDs on gastric phospholipid fluidity. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 3195–3206, 2008","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[],"research_interests":[{"id":89956,"name":"Pharmaceutical Sciences","url":"https://www.academia.edu/Documents/in/Pharmaceutical_Sciences"}],"urls":[{"id":2945780,"url":"http://doi.wiley.com/10.1002/jps.21218"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143036"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143036/Antibodies_against_a_peroxiredoxin_as_a_possible_marker_for_diagnosis_of_visceral_leishmaniasis_and_for_monitoring_the_efficacy_of_treatment"><img alt="Research paper thumbnail of Antibodies against a peroxiredoxin as a possible marker for diagnosis of visceral leishmaniasis and for monitoring the efficacy of treatment" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143036/Antibodies_against_a_peroxiredoxin_as_a_possible_marker_for_diagnosis_of_visceral_leishmaniasis_and_for_monitoring_the_efficacy_of_treatment">Antibodies against a peroxiredoxin as a possible marker for diagnosis of visceral leishmaniasis and for monitoring the efficacy of treatment</a></div><div class="wp-workCard_item"><span>Immunology Letters</span><span>, 2005</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143036"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143036"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143036; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143036]").text(description); $(".js-view-count[data-work-id=7143036]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143036; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143036']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143036, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=7143036]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143036,"title":"Antibodies against a peroxiredoxin as a possible marker for diagnosis of visceral leishmaniasis and for monitoring the efficacy of treatment","translated_title":"","metadata":{"publication_date":{"day":null,"month":null,"year":2005,"errors":{}},"publication_name":"Immunology Letters"},"translated_abstract":null,"internal_url":"https://www.academia.edu/7143036/Antibodies_against_a_peroxiredoxin_as_a_possible_marker_for_diagnosis_of_visceral_leishmaniasis_and_for_monitoring_the_efficacy_of_treatment","translated_internal_url":"","created_at":"2014-05-24T01:01:48.309-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Antibodies_against_a_peroxiredoxin_as_a_possible_marker_for_diagnosis_of_visceral_leishmaniasis_and_for_monitoring_the_efficacy_of_treatment","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":null,"owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[],"research_interests":[],"urls":[{"id":2945779,"url":"http://linkinghub.elsevier.com/retrieve/pii/S0165247805001057"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143035"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143035/Targeted_disruption_of_cytosolic_SIR2_deacetylase_discloses_its_essential_role_in_Leishmania_survival_and_proliferation"><img alt="Research paper thumbnail of Targeted disruption of cytosolic SIR2 deacetylase discloses its essential role in Leishmania survival and proliferation" class="work-thumbnail" src="https://attachments.academia-assets.com/48583953/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143035/Targeted_disruption_of_cytosolic_SIR2_deacetylase_discloses_its_essential_role_in_Leishmania_survival_and_proliferation">Targeted disruption of cytosolic SIR2 deacetylase discloses its essential role in Leishmania survival and proliferation</a></div><div class="wp-workCard_item"><span>Gene</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Proteins of the SIR2 family are characterized by a conserved catalytic domain that exerts unique ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Proteins of the SIR2 family are characterized by a conserved catalytic domain that exerts unique NAD-dependent deacetylase activity on histone and various other cellular substrates. Functional analyses of such proteins have been carried out in a number of prokaryotes and eukaryotes organisms but until now, none have described an essential function for any SIR2 genes. Here using genetic approach, we report that a cytosolic SIR2 homolog in Leishmania is determinant to parasite survival. L. infantum promastigote tolerates deletion of one wild-type LiSIR2 allele (LiSIR2+/−) but achievement of null chromosomal mutants (LiSIR2−/−) requires episomal rescue. Accordingly, plasmid cure shows that these parasites maintain episome even in absence of drug pressure. Though single LiSIR2 gene disruption (LiSIR2+/−) does not affect the growth of parasite in the promastigote form, axenic amastigotes display a marked reduction in their capacity to multiply in vitro inside macrophages and in vivo in Balb/c mice. Taken together these data support a stage specific requirement and/or activity of the Leishmania cytosolic SIR2 protein and reveal an unrelated essential function for the life cycle of this unicellular pathogenic organism. The lack of an effective vaccine against leishmaniasis, and the need for alternative drug treatments, makes LiSIR2 protein a new attractive therapeutic target. Gene 363 (2005) 85 -96 <a href="http://www.elsevier.com/locate/gene" rel="nofollow">www.elsevier.com/locate/gene</a> Abbreviations: LiSIR2, Leishmania infantum Silent Information Regulatory gene homologue; pXG-BSDLiSIR2 plasmid, plamid which confers resistance to Blasticidin and carrying the LiSIR2 gene; PFGE, Pulse field gel electrophoresis; NAD, nicotinamide-adenine dinucleotide; HDAC, histone deacetylase; WT, wild type parasite clone; neo and hyg, the neomycin phosphotransferase and the hygromicin phosphotransferase cassettes, respectively; ORF, open reading frame. ⁎ Corresponding author. Tel./</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="52e5f8a54450b83393277614402949af" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583953,"asset_id":7143035,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583953/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143035"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143035"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143035; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143035]").text(description); $(".js-view-count[data-work-id=7143035]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143035; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143035']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143035, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "52e5f8a54450b83393277614402949af" } } $('.js-work-strip[data-work-id=7143035]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143035,"title":"Targeted disruption of cytosolic SIR2 deacetylase discloses its essential role in Leishmania survival and proliferation","translated_title":"","metadata":{"ai_title_tag":"Role of Cytosolic SIR2 in Leishmania Survival and Proliferation","grobid_abstract":"Proteins of the SIR2 family are characterized by a conserved catalytic domain that exerts unique NAD-dependent deacetylase activity on histone and various other cellular substrates. 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Functional analyses of such proteins have been carried out in a number of prokaryotes and eukaryotes organisms but until now, none have described an essential function for any SIR2 genes. Here using genetic approach, we report that a cytosolic SIR2 homolog in Leishmania is determinant to parasite survival. L. infantum promastigote tolerates deletion of one wild-type LiSIR2 allele (LiSIR2+/−) but achievement of null chromosomal mutants (LiSIR2−/−) requires episomal rescue. Accordingly, plasmid cure shows that these parasites maintain episome even in absence of drug pressure. Though single LiSIR2 gene disruption (LiSIR2+/−) does not affect the growth of parasite in the promastigote form, axenic amastigotes display a marked reduction in their capacity to multiply in vitro inside macrophages and in vivo in Balb/c mice. Taken together these data support a stage specific requirement and/or activity of the Leishmania cytosolic SIR2 protein and reveal an unrelated essential function for the life cycle of this unicellular pathogenic organism. The lack of an effective vaccine against leishmaniasis, and the need for alternative drug treatments, makes LiSIR2 protein a new attractive therapeutic target. Gene 363 (2005) 85 -96 www.elsevier.com/locate/gene Abbreviations: LiSIR2, Leishmania infantum Silent Information Regulatory gene homologue; pXG-BSDLiSIR2 plasmid, plamid which confers resistance to Blasticidin and carrying the LiSIR2 gene; PFGE, Pulse field gel electrophoresis; NAD, nicotinamide-adenine dinucleotide; HDAC, histone deacetylase; WT, wild type parasite clone; neo and hyg, the neomycin phosphotransferase and the hygromicin phosphotransferase cassettes, respectively; ORF, open reading frame. ⁎ Corresponding author. Tel./","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583953,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583953/thumbnails/1.jpg","file_name":"Targeted_disruption_of_cytosolic_SIR2_de20160905-30903-zdb7ox.pdf","download_url":"https://www.academia.edu/attachments/48583953/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Targeted_disruption_of_cytosolic_SIR2_de.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583953/Targeted_disruption_of_cytosolic_SIR2_de20160905-30903-zdb7ox-libre.pdf?1473073944=\u0026response-content-disposition=attachment%3B+filename%3DTargeted_disruption_of_cytosolic_SIR2_de.pdf\u0026Expires=1736775918\u0026Signature=Dr2hd8SBclJBzVcv8RRUivCqOvg8CMKBxsZgACbUBQeRpqKdFJ8XW64tVuXdykNYEO-QR8~pBWbt3MJKdSm3xoN24BwseQfwihgCLGuC3VBwZBWCpq2O6Avig8vtp1BJX11oUDv-OUdjwbe-JADspL3a4XBNHvQShz7kJQgcWcFFtA-fb-7yg30y5HOmQr07AviGw3b1mE4A9TFRE6qHikPBRcwDe9h0EvYbZ0OIFbETowziBbkRHrWqCe4rQKyPvlY3K0X6moab~fgXU43D8ThzX5efR-2TDhHJeXw8oSjALHUfVnXvGpA0AVrDVqhTymH9uwAr9e~C6~5hljAyrg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":156,"name":"Genetics","url":"https://www.academia.edu/Documents/in/Genetics"},{"id":9113,"name":"Cell Cycle","url":"https://www.academia.edu/Documents/in/Cell_Cycle"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":181936,"name":"Gene","url":"https://www.academia.edu/Documents/in/Gene"},{"id":182962,"name":"Life Cycle","url":"https://www.academia.edu/Documents/in/Life_Cycle"},{"id":208178,"name":"Sirtuins","url":"https://www.academia.edu/Documents/in/Sirtuins"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation"},{"id":789996,"name":"Leishmania infantum","url":"https://www.academia.edu/Documents/in/Leishmania_infantum"},{"id":809882,"name":"Base Sequence","url":"https://www.academia.edu/Documents/in/Base_Sequence"},{"id":894903,"name":"Gene Disruption","url":"https://www.academia.edu/Documents/in/Gene_Disruption"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival"},{"id":1592916,"name":"Drug treatment","url":"https://www.academia.edu/Documents/in/Drug_treatment"}],"urls":[{"id":2945778,"url":"http://www.sciencedirect.com/science/article/pii/S0378111905004312"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143034"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143034/Differential_effects_of_polyamine_derivative_compounds_against_promastigotes_and_axenic_amastigotes"><img alt="Research paper thumbnail of Differential effects of polyamine derivative compounds against promastigotes and axenic amastigotes" class="work-thumbnail" src="https://attachments.academia-assets.com/48583932/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143034/Differential_effects_of_polyamine_derivative_compounds_against_promastigotes_and_axenic_amastigotes">Differential effects of polyamine derivative compounds against promastigotes and axenic amastigotes</a></div><div class="wp-workCard_item"><span>International Journal for Parasitology</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The natural polyamines are ubiquitous polycationic compounds that play important biological funct...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The natural polyamines are ubiquitous polycationic compounds that play important biological functions in cell growth and differentiation. In the case of protozoan species that are causative agents of important human diseases such as Leishmaniasis, an exogenous supply of polyamines supports parasite proliferation. In the present study, we have investigated the effect of three polyamine derivatives, (namely bisnaphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd) and spermine (BNIPSpm)), on the proliferative stages of Leishmania infantum, the causative agent of visceral leishmaniasis in the Mediterranean basin. A significant reduction of promastigotes and axenic amastigotes growth was observed in the presence of increasing concentrations of the drugs, although the mechanisms leading to the parasite growth arrest seems to be different. Indeed, by using a number of biochemical approaches to analyse the alterations that occurred during early stages of parasite-drug interaction (i.e. membrane phosphatidylserine exposure measured by annexin V binding, DNA fragmentation, deoxynucleotidyltranferase-mediated dUTP end labelin (TUNEL), mitochondrial transmembrane potential loss), we showed that the drugs had the capacity to induce the death of promastigotes by a mechanism that shares many features with metazoan apoptosis. Surprisingly, the amastigotes did not behave in a similar way to promastigotes. The drug inhibitory effect on amastigotes growth and the absence of propidium iodide labelling may suggest that the compounds are acting as cytostatic substances. Although, the mechanisms of action of these compounds have yet to be elucidated, the above data show for the first time that polyamine derivatives may act differentially on the Leishmania parasite stages. Further chemical modifications are needed to make the polyamine derivatives as well as other analogues able to target the amastigote stage of the parasite. q</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="b7904a893a506074592e8bd5afd0a4ac" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583932,"asset_id":7143034,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583932/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143034"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143034"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143034; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143034]").text(description); $(".js-view-count[data-work-id=7143034]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143034; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143034']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143034, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "b7904a893a506074592e8bd5afd0a4ac" } } $('.js-work-strip[data-work-id=7143034]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143034,"title":"Differential effects of polyamine derivative compounds against promastigotes and axenic amastigotes","translated_title":"","metadata":{"grobid_abstract":"The natural polyamines are ubiquitous polycationic compounds that play important biological functions in cell growth and differentiation. 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In the case of protozoan species that are causative agents of important human diseases such as Leishmaniasis, an exogenous supply of polyamines supports parasite proliferation. In the present study, we have investigated the effect of three polyamine derivatives, (namely bisnaphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd) and spermine (BNIPSpm)), on the proliferative stages of Leishmania infantum, the causative agent of visceral leishmaniasis in the Mediterranean basin. A significant reduction of promastigotes and axenic amastigotes growth was observed in the presence of increasing concentrations of the drugs, although the mechanisms leading to the parasite growth arrest seems to be different. Indeed, by using a number of biochemical approaches to analyse the alterations that occurred during early stages of parasite-drug interaction (i.e. membrane phosphatidylserine exposure measured by annexin V binding, DNA fragmentation, deoxynucleotidyltranferase-mediated dUTP end labelin (TUNEL), mitochondrial transmembrane potential loss), we showed that the drugs had the capacity to induce the death of promastigotes by a mechanism that shares many features with metazoan apoptosis. Surprisingly, the amastigotes did not behave in a similar way to promastigotes. The drug inhibitory effect on amastigotes growth and the absence of propidium iodide labelling may suggest that the compounds are acting as cytostatic substances. Although, the mechanisms of action of these compounds have yet to be elucidated, the above data show for the first time that polyamine derivatives may act differentially on the Leishmania parasite stages. Further chemical modifications are needed to make the polyamine derivatives as well as other analogues able to target the amastigote stage of the parasite. q","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583932,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583932/thumbnails/1.jpg","file_name":"j.ijpara.2005.01.00820160905-22395-1sk3d09.pdf","download_url":"https://www.academia.edu/attachments/48583932/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Differential_effects_of_polyamine_deriva.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583932/j.ijpara.2005.01.00820160905-22395-1sk3d09-libre.pdf?1473073944=\u0026response-content-disposition=attachment%3B+filename%3DDifferential_effects_of_polyamine_deriva.pdf\u0026Expires=1736775918\u0026Signature=ga-awkbt0tmafLEkYeaKZYgXZWUUIKd2cu5paokoZyRBrmUfIgN60PYng70CAPeXBzqn5eQ2e5wfgYBNh-7o2PxiHSIbQVHtkwzcN99FPKHfawWWbRBvFTEzeFUB0eVrcGUrUC-h6CleiV3QfZ9yqpObTh9QOiIT-fI-910GnuLDCtjwPj~5x7kjHe8lFudU2JwLyYpY~AfQ1xTI7z4nVt2-lVegrlkqETV8WbYILtaE5-3CjqBVBMyqzdWpbeoF-zejDmE44Q2VPhH3AuYlsWPNIneWhq-Z6wpQcyDCwFlN9NP-zECXNMVrVog0r5z3Kk5yirXLtHOR1TNuCicKMA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":159,"name":"Microbiology","url":"https://www.academia.edu/Documents/in/Microbiology"},{"id":173,"name":"Zoology","url":"https://www.academia.edu/Documents/in/Zoology"},{"id":6599,"name":"Flow Cytometry","url":"https://www.academia.edu/Documents/in/Flow_Cytometry"},{"id":15719,"name":"Mitochondria","url":"https://www.academia.edu/Documents/in/Mitochondria"},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis"},{"id":83972,"name":"Permeability","url":"https://www.academia.edu/Documents/in/Permeability"},{"id":128004,"name":"Visceral Leishmaniasis","url":"https://www.academia.edu/Documents/in/Visceral_Leishmaniasis"},{"id":195950,"name":"Quinolones","url":"https://www.academia.edu/Documents/in/Quinolones"},{"id":323597,"name":"Fluorescent Antibody Technique","url":"https://www.academia.edu/Documents/in/Fluorescent_Antibody_Technique"},{"id":421780,"name":"Putrescine","url":"https://www.academia.edu/Documents/in/Putrescine"},{"id":421781,"name":"Spermine","url":"https://www.academia.edu/Documents/in/Spermine"},{"id":421782,"name":"Spermidine","url":"https://www.academia.edu/Documents/in/Spermidine"},{"id":537505,"name":"For","url":"https://www.academia.edu/Documents/in/For"},{"id":644860,"name":"Veterinary Sciences","url":"https://www.academia.edu/Documents/in/Veterinary_Sciences"},{"id":725615,"name":"Mechanism of action","url":"https://www.academia.edu/Documents/in/Mechanism_of_action"},{"id":789996,"name":"Leishmania infantum","url":"https://www.academia.edu/Documents/in/Leishmania_infantum"},{"id":833228,"name":"Human Disease","url":"https://www.academia.edu/Documents/in/Human_Disease"},{"id":966608,"name":"Mediterranean Basin","url":"https://www.academia.edu/Documents/in/Mediterranean_Basin"},{"id":979632,"name":"Drug Interaction","url":"https://www.academia.edu/Documents/in/Drug_Interaction"},{"id":1335154,"name":"Propidium Iodide","url":"https://www.academia.edu/Documents/in/Propidium_Iodide"},{"id":1418721,"name":"Chemical Modification","url":"https://www.academia.edu/Documents/in/Chemical_Modification"},{"id":1954130,"name":"Cell Growth","url":"https://www.academia.edu/Documents/in/Cell_Growth"},{"id":2256666,"name":"DNA fragmentation","url":"https://www.academia.edu/Documents/in/DNA_fragmentation"}],"urls":[{"id":2945777,"url":"http://linkinghub.elsevier.com/retrieve/pii/S0020751905000391"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143033"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143033/Evaluation_of_the_immune_response_following_a_short_oral_vaccination_schedule_with_hepatitis_B_antigen_encapsulated_into_alginate_coated_chitosan_nanoparticles"><img alt="Research paper thumbnail of Evaluation of the immune response following a short oral vaccination schedule with hepatitis B antigen encapsulated into alginate-coated chitosan nanoparticles" class="work-thumbnail" src="https://attachments.academia-assets.com/48583981/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143033/Evaluation_of_the_immune_response_following_a_short_oral_vaccination_schedule_with_hepatitis_B_antigen_encapsulated_into_alginate_coated_chitosan_nanoparticles">Evaluation of the immune response following a short oral vaccination schedule with hepatitis B antigen encapsulated into alginate-coated chitosan nanoparticles</a></div><div class="wp-workCard_item"><span>European Journal of Pharmaceutical Sciences</span><span>, 2007</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Hepatitis B surface antigen CpG oligodeoxynucleotide Alginate-coated chitosan nanoparticles Vacci...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Hepatitis B surface antigen CpG oligodeoxynucleotide Alginate-coated chitosan nanoparticles Vaccines a b s t r a c t The purpose of this work was to assess the ability of recombinant hepatitis B vaccine, encapsulated in alginate-coated chitosan nanoparticles, to induce local and systemic immune responses following oral vaccination. The antigen was administered either alone or in combination with the immunopotentiator, synthetic oligodeoxynucleotide containing immunostimulatory CpG motif (CpG ODN) as adjuvant, and associated or not with the alginate-coated chitosan nanoparticles. After two immunizations the group I (HBsAg associated with nanoparticles) and the group VI (HBsAg and CpG, both associated with nanoparticles) showed enhanced immune responses. Both groups showed significant higher values of the CD69 expression in CD4+ and CD8+ T-lymphocytes and lower values of this marker in B lymphocytes. Moreover, a strongest proliferative response of the splenocytes, ex vivo stimulated with concanavalin A, was observed in the same groups. Although with a presence of non-responder mice within the groups, only mice of the groups I and VI elicited the generation of anti-HBsAg antibodies detected in serum (IgG) and in the intestinal washings (sIgA). The results demonstrated that coated chitosan nanoparticles might have potential for being used as a deliver system for oral vaccination with the recombinant hepatitis B surface antigen. (O. Borges).</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="ca2d7c7d0bc091339b4e357b57a4a9c2" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583981,"asset_id":7143033,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583981/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143033"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143033"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143033; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143033]").text(description); $(".js-view-count[data-work-id=7143033]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143033; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143033']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143033, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "ca2d7c7d0bc091339b4e357b57a4a9c2" } } $('.js-work-strip[data-work-id=7143033]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143033,"title":"Evaluation of the immune response following a short oral vaccination schedule with hepatitis B antigen encapsulated into alginate-coated chitosan nanoparticles","translated_title":"","metadata":{"grobid_abstract":"Hepatitis B surface antigen CpG oligodeoxynucleotide Alginate-coated chitosan nanoparticles Vaccines a b s t r a c t The purpose of this work was to assess the ability of recombinant hepatitis B vaccine, encapsulated in alginate-coated chitosan nanoparticles, to induce local and systemic immune responses following oral vaccination. The antigen was administered either alone or in combination with the immunopotentiator, synthetic oligodeoxynucleotide containing immunostimulatory CpG motif (CpG ODN) as adjuvant, and associated or not with the alginate-coated chitosan nanoparticles. After two immunizations the group I (HBsAg associated with nanoparticles) and the group VI (HBsAg and CpG, both associated with nanoparticles) showed enhanced immune responses. Both groups showed significant higher values of the CD69 expression in CD4+ and CD8+ T-lymphocytes and lower values of this marker in B lymphocytes. Moreover, a strongest proliferative response of the splenocytes, ex vivo stimulated with concanavalin A, was observed in the same groups. Although with a presence of non-responder mice within the groups, only mice of the groups I and VI elicited the generation of anti-HBsAg antibodies detected in serum (IgG) and in the intestinal washings (sIgA). The results demonstrated that coated chitosan nanoparticles might have potential for being used as a deliver system for oral vaccination with the recombinant hepatitis B surface antigen. (O. 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The antigen was administered either alone or in combination with the immunopotentiator, synthetic oligodeoxynucleotide containing immunostimulatory CpG motif (CpG ODN) as adjuvant, and associated or not with the alginate-coated chitosan nanoparticles. After two immunizations the group I (HBsAg associated with nanoparticles) and the group VI (HBsAg and CpG, both associated with nanoparticles) showed enhanced immune responses. Both groups showed significant higher values of the CD69 expression in CD4+ and CD8+ T-lymphocytes and lower values of this marker in B lymphocytes. Moreover, a strongest proliferative response of the splenocytes, ex vivo stimulated with concanavalin A, was observed in the same groups. Although with a presence of non-responder mice within the groups, only mice of the groups I and VI elicited the generation of anti-HBsAg antibodies detected in serum (IgG) and in the intestinal washings (sIgA). 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The effects of these ESA on the host cell function may participate in the establishment of a successful infection, in which the parasite persists for a sufficient period of time to complete its life cycle. A number of regulatory components or processes originating from the parasite that control or regulate the metabolism and the growth of host cell have been identified. The purpose of the present review is to analyze some of the current data related to the parasite ESA that interfere with the host cell physiology. Special attention is given to members of conserved protein families demonstrating remarkable diversity and plasticity of function (ie, glutathione S-transferases and related molecules; members of the trans-sialidase and mucin family; and members of the ribosomal protein family). The identification of parasite target molecules and the elucidation of their mode of action toward the host cell represents a step forward in efforts aimed at an immunotherapeutic or pharmacological control of parasitic infection.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="dbc3cfb4c2904aeb83f9ed40de26a963" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583885,"asset_id":7143032,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583885/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143032"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143032"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143032; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143032]").text(description); $(".js-view-count[data-work-id=7143032]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143032; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143032']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143032, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "dbc3cfb4c2904aeb83f9ed40de26a963" } } $('.js-work-strip[data-work-id=7143032]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143032,"title":"Host Cell Phenotypic Variability Induced by Trypanosomatid-Parasite-Released Immunomodulatory Factors: Physiopathological Implications","translated_title":"","metadata":{"grobid_abstract":"The parasitic protozoa Trypanosoma cruzi and Leishmania sp release a variety of molecules into their mammalian hosts (ESA: excretory-secretory products). 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Du...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The host innate immune system represents the first line of defense against invasive pathogens. During the crucial early stages of infection, the host innate immune system must be able to rapidly detect and respond to foreign pathogens, enabling an efficient and successful adaptative immune response. Leishmania parasites are obligate intracellular eukaryotic pathogens living inside cells of the mononuclear phagocytic system. Recent data has proven distinct roles of various phagocytic cells, such as neutrophils, macrophages and dendritic cells during Leishmania infection. There is growing evidence that Leishmania modifies antigen presentation, apoptosis and immunoregulatory functions on these cells, leading to persistent and chronic infection. At the molecular level, the Toll-like receptors (TLR) family is a major player in the early host-pathogen interaction. The TLRs expressed intracellularly or at the surface of the cells involved in the innate immune response recognize conserved structures on foreign pathogens, such as Leishmania, playing a pivotal role in triggering innate and adaptative immune responses. Nonetheless, the same TLRs can be considered as a potential strategic target used by these organisms for their own advantage. In this review, we discussed the findings on the cellular processes involved in the innate host defense against intracellular pathogens, focusing on the Leishmania infection, from the initial host-parasite interactions involved in the parasite recognition to the mechanisms employed to eliminate the pathogen, presenting new data on the role of TLR2 in visceral leishmaniasis.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="3f2d177a2294a9246b2369815de39a30" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583957,"asset_id":7143031,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583957/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143031"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143031"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143031; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143031]").text(description); $(".js-view-count[data-work-id=7143031]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143031; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143031']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143031, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "3f2d177a2294a9246b2369815de39a30" } } $('.js-work-strip[data-work-id=7143031]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143031,"title":"Recognition of Leishmania Parasites by Innate Immunity","translated_title":"","metadata":{"grobid_abstract":"The host innate immune system represents the first line of defense against invasive pathogens. 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The TLRs expressed intracellularly or at the surface of the cells involved in the innate immune response recognize conserved structures on foreign pathogens, such as Leishmania, playing a pivotal role in triggering innate and adaptative immune responses. Nonetheless, the same TLRs can be considered as a potential strategic target used by these organisms for their own advantage. In this review, we discussed the findings on the cellular processes involved in the innate host defense against intracellular pathogens, focusing on the Leishmania infection, from the initial host-parasite interactions involved in the parasite recognition to the mechanisms employed to eliminate the pathogen, presenting new data on the role of TLR2 in visceral leishmaniasis.","publication_date":{"day":null,"month":null,"year":2009,"errors":{}},"publication_name":"Immunology, Endocrine \u0026 Metabolic Agents - Medicinal Chemistry (formerly Current Medicinal Chemistry - Immunology, Endocrine \u0026 Metabolic Agents)","grobid_abstract_attachment_id":48583957},"translated_abstract":null,"internal_url":"https://www.academia.edu/7143031/Recognition_of_Leishmania_Parasites_by_Innate_Immunity","translated_internal_url":"","created_at":"2014-05-24T01:01:46.848-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583957,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583957/thumbnails/1.jpg","file_name":"Recognition_of_Leishmania_Parasites_by_I20160905-4206-1pcsvlu.pdf","download_url":"https://www.academia.edu/attachments/48583957/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Recognition_of_Leishmania_Parasites_by_I.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583957/Recognition_of_Leishmania_Parasites_by_I20160905-4206-1pcsvlu-libre.pdf?1473073953=\u0026response-content-disposition=attachment%3B+filename%3DRecognition_of_Leishmania_Parasites_by_I.pdf\u0026Expires=1736775918\u0026Signature=dfadb0Nn4R7xIUO-TzJ0eZ76LO~Fblxl644bV5C-lCmiV-N1t4QgwAvJmZU9Ok2c0VeXXq2ewjwj2vwcAslwLjHEOWgetT9y4yppnr0SzZAJckgezTjgOC0RVOGji18~Ygzzmf8XJWz614O8PuxAc28O2Uezw5pHYEzc9i1wK6fG1sfx5RYRVetSMs3b8IAFhgktDIjykGPe0CF3hKTf-U47l~2aVPGCqHlQtBFvfcZxqo2c7i9Va0DyOhL0wdXpuHWbj6elgX30e9dV-eTR9lLoPDsjqkzKD~VeyVyVuLJqVY~twf4OW2nKnSrYRvp~2axAynECQnaOPoDyqccFpQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Recognition_of_Leishmania_Parasites_by_Innate_Immunity","translated_slug":"","page_count":18,"language":"en","content_type":"Work","summary":"The host innate immune system represents the first line of defense against invasive pathogens. During the crucial early stages of infection, the host innate immune system must be able to rapidly detect and respond to foreign pathogens, enabling an efficient and successful adaptative immune response. Leishmania parasites are obligate intracellular eukaryotic pathogens living inside cells of the mononuclear phagocytic system. Recent data has proven distinct roles of various phagocytic cells, such as neutrophils, macrophages and dendritic cells during Leishmania infection. There is growing evidence that Leishmania modifies antigen presentation, apoptosis and immunoregulatory functions on these cells, leading to persistent and chronic infection. At the molecular level, the Toll-like receptors (TLR) family is a major player in the early host-pathogen interaction. The TLRs expressed intracellularly or at the surface of the cells involved in the innate immune response recognize conserved structures on foreign pathogens, such as Leishmania, playing a pivotal role in triggering innate and adaptative immune responses. Nonetheless, the same TLRs can be considered as a potential strategic target used by these organisms for their own advantage. In this review, we discussed the findings on the cellular processes involved in the innate host defense against intracellular pathogens, focusing on the Leishmania infection, from the initial host-parasite interactions involved in the parasite recognition to the mechanisms employed to eliminate the pathogen, presenting new data on the role of TLR2 in visceral leishmaniasis.","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583957,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583957/thumbnails/1.jpg","file_name":"Recognition_of_Leishmania_Parasites_by_I20160905-4206-1pcsvlu.pdf","download_url":"https://www.academia.edu/attachments/48583957/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Recognition_of_Leishmania_Parasites_by_I.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583957/Recognition_of_Leishmania_Parasites_by_I20160905-4206-1pcsvlu-libre.pdf?1473073953=\u0026response-content-disposition=attachment%3B+filename%3DRecognition_of_Leishmania_Parasites_by_I.pdf\u0026Expires=1736775918\u0026Signature=dfadb0Nn4R7xIUO-TzJ0eZ76LO~Fblxl644bV5C-lCmiV-N1t4QgwAvJmZU9Ok2c0VeXXq2ewjwj2vwcAslwLjHEOWgetT9y4yppnr0SzZAJckgezTjgOC0RVOGji18~Ygzzmf8XJWz614O8PuxAc28O2Uezw5pHYEzc9i1wK6fG1sfx5RYRVetSMs3b8IAFhgktDIjykGPe0CF3hKTf-U47l~2aVPGCqHlQtBFvfcZxqo2c7i9Va0DyOhL0wdXpuHWbj6elgX30e9dV-eTR9lLoPDsjqkzKD~VeyVyVuLJqVY~twf4OW2nKnSrYRvp~2axAynECQnaOPoDyqccFpQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":24706,"name":"Innate immunity","url":"https://www.academia.edu/Documents/in/Innate_immunity"},{"id":126964,"name":"Endocrine","url":"https://www.academia.edu/Documents/in/Endocrine"}],"urls":[{"id":2945774,"url":"http://openurl.ingenta.com/content/xref?genre=article\u0026issn=1871-5222\u0026volume=9\u0026issue=2\u0026spage=106"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143030"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143030/Effect_of_anti_inflammatory_drugs_on_splenocyte_membrane_fluidity"><img alt="Research paper thumbnail of Effect of anti-inflammatory drugs on splenocyte membrane fluidity" class="work-thumbnail" src="https://attachments.academia-assets.com/48583897/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143030/Effect_of_anti_inflammatory_drugs_on_splenocyte_membrane_fluidity">Effect of anti-inflammatory drugs on splenocyte membrane fluidity</a></div><div class="wp-workCard_item"><span>Analytical Biochemistry</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">In this study, Xuorescence anisotropy measurements were performed using the Xuorescent probe 1,6-...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">In this study, Xuorescence anisotropy measurements were performed using the Xuorescent probe 1,6-diphenyl-1,3,5-hexatriene to investigate the eVects on membrane Xuidity resulting from the interaction between nonsteroidal anti-inXammatory drugs (NSA-IDs)-indomethacin, diclofenac, piroxicam, tenoxicam, indoprofen, clonixin, and etodolac-and mouse splenocyte membranes. This study was performed in splenocyte membranes because most of the Xuidity studies have been performed in membrane models; thus, clear correlations of the pharmacological action of drugs with molecular eVects at the cellular membrane level were lacking. Besides providing a basis for studying the molecular mechanism of pharmacological action of NSAIDs, this research provides a data analysis of steady-state anisotropy measurements, taking into account that the probe itself strongly inXuences the data given that this problem is usually overlooked. Results show that the anti-inXammatory drugs indomethacin, diclofenac, piroxicam, and tenoxicam increase the membrane Xuidity in a concentration-dependent manner. Their order of eVectiveness reXected in their respective IC 50 values (concentration of each NSAID required to increase the Xuidizing eVect ratio by 50%) is as follows: tenoxicam > piroxicam > indomethacin > clonixin. For the other drugs, the perturbation in membrane Xuidity is not evident under these circumstances. </span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="3319b971e112a72e47a80d72b4fe3932" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48583897,"asset_id":7143030,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48583897/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="7143030"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="7143030"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 7143030; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=7143030]").text(description); $(".js-view-count[data-work-id=7143030]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 7143030; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='7143030']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 7143030, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "3319b971e112a72e47a80d72b4fe3932" } } $('.js-work-strip[data-work-id=7143030]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":7143030,"title":"Effect of anti-inflammatory drugs on splenocyte membrane fluidity","translated_title":"","metadata":{"grobid_abstract":"In this study, Xuorescence anisotropy measurements were performed using the Xuorescent probe 1,6-diphenyl-1,3,5-hexatriene to investigate the eVects on membrane Xuidity resulting from the interaction between nonsteroidal anti-inXammatory drugs (NSA-IDs)-indomethacin, diclofenac, piroxicam, tenoxicam, indoprofen, clonixin, and etodolac-and mouse splenocyte membranes. This study was performed in splenocyte membranes because most of the Xuidity studies have been performed in membrane models; thus, clear correlations of the pharmacological action of drugs with molecular eVects at the cellular membrane level were lacking. Besides providing a basis for studying the molecular mechanism of pharmacological action of NSAIDs, this research provides a data analysis of steady-state anisotropy measurements, taking into account that the probe itself strongly inXuences the data given that this problem is usually overlooked. Results show that the anti-inXammatory drugs indomethacin, diclofenac, piroxicam, and tenoxicam increase the membrane Xuidity in a concentration-dependent manner. Their order of eVectiveness reXected in their respective IC 50 values (concentration of each NSAID required to increase the Xuidizing eVect ratio by 50%) is as follows: tenoxicam \u003e piroxicam \u003e indomethacin \u003e clonixin. For the other drugs, the perturbation in membrane Xuidity is not evident under these circumstances. ","publication_date":{"day":null,"month":null,"year":2005,"errors":{}},"publication_name":"Analytical Biochemistry","grobid_abstract_attachment_id":48583897},"translated_abstract":null,"internal_url":"https://www.academia.edu/7143030/Effect_of_anti_inflammatory_drugs_on_splenocyte_membrane_fluidity","translated_internal_url":"","created_at":"2014-05-24T01:01:46.515-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":12324004,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":48583897,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583897/thumbnails/1.jpg","file_name":"j.ab.2004.12.02320160905-26881-3567ip.pdf","download_url":"https://www.academia.edu/attachments/48583897/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Effect_of_anti_inflammatory_drugs_on_spl.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583897/j.ab.2004.12.02320160905-26881-3567ip-libre.pdf?1473073946=\u0026response-content-disposition=attachment%3B+filename%3DEffect_of_anti_inflammatory_drugs_on_spl.pdf\u0026Expires=1736775919\u0026Signature=VoMKScCUNXimEkirSDSa~TyeuZhyEBR3mae4Dt1DBomMS6yH8d831Ae4ERZdJiOG-FLgcBM9aKFflk8yusfFg-Ot16X2YDb6pHADordeCb4WRbT6kQbVS-CP2ObhtuvOUaqYeAYJyO2FEJ4~U4GV7pjWCfp2AypDxErezCPe4wqsqgIQOjoxgprlJ1911CwaFR8PzpcZlBnchZggVFsierXyhi50auiBlHglnlLlIDght~yjZOze27ylNFNBGzs1GNOkEwkUJm6f4NRud0HpOq2b0w6N5tBwaaq~KgN61CbrwQ~jookqRQqAD~SfM9Uia5UnMryR36bfZZQ-jpBsLg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Effect_of_anti_inflammatory_drugs_on_splenocyte_membrane_fluidity","translated_slug":"","page_count":6,"language":"en","content_type":"Work","summary":"In this study, Xuorescence anisotropy measurements were performed using the Xuorescent probe 1,6-diphenyl-1,3,5-hexatriene to investigate the eVects on membrane Xuidity resulting from the interaction between nonsteroidal anti-inXammatory drugs (NSA-IDs)-indomethacin, diclofenac, piroxicam, tenoxicam, indoprofen, clonixin, and etodolac-and mouse splenocyte membranes. This study was performed in splenocyte membranes because most of the Xuidity studies have been performed in membrane models; thus, clear correlations of the pharmacological action of drugs with molecular eVects at the cellular membrane level were lacking. Besides providing a basis for studying the molecular mechanism of pharmacological action of NSAIDs, this research provides a data analysis of steady-state anisotropy measurements, taking into account that the probe itself strongly inXuences the data given that this problem is usually overlooked. Results show that the anti-inXammatory drugs indomethacin, diclofenac, piroxicam, and tenoxicam increase the membrane Xuidity in a concentration-dependent manner. Their order of eVectiveness reXected in their respective IC 50 values (concentration of each NSAID required to increase the Xuidizing eVect ratio by 50%) is as follows: tenoxicam \u003e piroxicam \u003e indomethacin \u003e clonixin. For the other drugs, the perturbation in membrane Xuidity is not evident under these circumstances. ","owner":{"id":12324004,"first_name":"Joana","middle_initials":null,"last_name":"Tavares","page_name":"JoanaTavares2","domain_name":"independent","created_at":"2014-05-24T01:00:42.222-07:00","display_name":"Joana Tavares","url":"https://independent.academia.edu/JoanaTavares2"},"attachments":[{"id":48583897,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/48583897/thumbnails/1.jpg","file_name":"j.ab.2004.12.02320160905-26881-3567ip.pdf","download_url":"https://www.academia.edu/attachments/48583897/download_file?st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&st=MTczNjc3MjMxOSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Effect_of_anti_inflammatory_drugs_on_spl.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/48583897/j.ab.2004.12.02320160905-26881-3567ip-libre.pdf?1473073946=\u0026response-content-disposition=attachment%3B+filename%3DEffect_of_anti_inflammatory_drugs_on_spl.pdf\u0026Expires=1736775919\u0026Signature=VoMKScCUNXimEkirSDSa~TyeuZhyEBR3mae4Dt1DBomMS6yH8d831Ae4ERZdJiOG-FLgcBM9aKFflk8yusfFg-Ot16X2YDb6pHADordeCb4WRbT6kQbVS-CP2ObhtuvOUaqYeAYJyO2FEJ4~U4GV7pjWCfp2AypDxErezCPe4wqsqgIQOjoxgprlJ1911CwaFR8PzpcZlBnchZggVFsierXyhi50auiBlHglnlLlIDght~yjZOze27ylNFNBGzs1GNOkEwkUJm6f4NRud0HpOq2b0w6N5tBwaaq~KgN61CbrwQ~jookqRQqAD~SfM9Uia5UnMryR36bfZZQ-jpBsLg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":524,"name":"Analytical Chemistry","url":"https://www.academia.edu/Documents/in/Analytical_Chemistry"},{"id":4205,"name":"Data Analysis","url":"https://www.academia.edu/Documents/in/Data_Analysis"},{"id":18529,"name":"Fluorescent Dyes and Reagents","url":"https://www.academia.edu/Documents/in/Fluorescent_Dyes_and_Reagents"},{"id":35637,"name":"Molecular Mechanics","url":"https://www.academia.edu/Documents/in/Molecular_Mechanics"},{"id":49018,"name":"Spleen","url":"https://www.academia.edu/Documents/in/Spleen"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":132569,"name":"Analytical","url":"https://www.academia.edu/Documents/in/Analytical"},{"id":204350,"name":"Anti-inflammatory agents","url":"https://www.academia.edu/Documents/in/Anti-inflammatory_agents"},{"id":234860,"name":"Steady state","url":"https://www.academia.edu/Documents/in/Steady_state"},{"id":452441,"name":"Fluorescent probes","url":"https://www.academia.edu/Documents/in/Fluorescent_probes"},{"id":539887,"name":"Fluorescence polarization","url":"https://www.academia.edu/Documents/in/Fluorescence_polarization"},{"id":639922,"name":"Fluorescence anisotropy","url":"https://www.academia.edu/Documents/in/Fluorescence_anisotropy"},{"id":806387,"name":"Analytical Biochemistry","url":"https://www.academia.edu/Documents/in/Analytical_Biochemistry"},{"id":1465015,"name":"Membrane Fluidity","url":"https://www.academia.edu/Documents/in/Membrane_Fluidity"},{"id":1681026,"name":"Biochemistry and cell biology","url":"https://www.academia.edu/Documents/in/Biochemistry_and_cell_biology"},{"id":2468093,"name":"Cell Membrane","url":"https://www.academia.edu/Documents/in/Cell_Membrane"}],"urls":[{"id":2945773,"url":"http://www.sciencedirect.com/science/article/pii/S0003269705000035"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="7143029"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/7143029/Characterization_of_the_anti_Leishmania_effect_induced_by_cisplatin_an_anticancer_drug"><img alt="Research paper thumbnail of Characterization of the anti- Leishmania effect induced by cisplatin, an anticancer drug" class="work-thumbnail" src="https://attachments.academia-assets.com/48583900/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/7143029/Characterization_of_the_anti_Leishmania_effect_induced_by_cisplatin_an_anticancer_drug">Characterization of the anti- Leishmania effect induced by cisplatin, an anticancer drug</a></div><div class="wp-workCard_item"><span>Acta Tropica</span><span>, 2007</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The cis-diamminedichloroplatinum(II), known as cis-DDP or cisplatin is a widely used drug in canc...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The cis-diamminedichloroplatinum(II), known as cis-DDP or cisplatin is a widely used drug in cancer chemotherapy. Although a recent study has shown the anti-Leishmania activity of some cis-DDP derivatives, the cytotoxic properties were measured only on promastigotes, the insect vector form of the parasite. In this study the effect of cis-DDP on promastigotes and amastigotes, the vertebrate stage of the parasite is reported. The IC 50 , determined by flow cytometry, after 72 h of drug incubation was four times higher, 7.73 ± 1.03 M in the case of promastigotes compared to axenic amastigotes, 1.88 ± 0.10 M. In intracellular amastigotes the IC 50 , determined by counting the parasite index was 1.85 ± 0.22 M. By using flow cytometry, two patterns of cell cycle changes was observed: cis-DDP treated promastigotes and amastigotes accumulated in S phase and G2 phase, respectively. The cis-DDP response was also found to involve an "apoptosis-like" death of both promastigotes and amastigotes. However, DNA fragmentation was only detected in promastigote forms. In contrast mitochondrial transmembrane potential loss was observed for both stages of the parasite. Upon incubation of parasites with the drug an increase on GSH and GSSG levels and reactive oxygen species could be detected in the case of promastigote. Moreover, a slight increase of GSH level was detected on amastigote form. Taken together, these observations indicate that amastigotes are more sensitive to cis-DDP when compared to promastigotes. 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