1,721,113 research outputs found
Trypanosoma brucei peptidase inhibitors.Immunolocalization, secretion and potential use as targets for therapy
Get PDFAs peptidases encontram-se envolvidas em diversas funções biológicas possuindo um papel importante na patogenicidade de várias infecções parasitárias. Em mamíferos, a actividade peptidica é controlada por inibidores endógenos, como as cistatinas e as serpinas. Os genes que codificam para inibidores homólogos às cistatinas e serpinas de mamíferos, encontram-se ausentes do genoma de tripanossomatídeos. A ecotina é uma proteína de Escherichia coli, capaz de inibir uma grande variedade de peptidases serínicas da família S1A, tais como a tripsina. Existem duas proteínas do tipo da ecotina em T. brucei, ISP1 e ISP2. A ausência de peptidases sensíveis à acção dos ISPs no genoma de Trypanosoma brucei, sugere que estes tenham como alvo as peptidases serínicas do hospedeiro. Linhas celulares de T. brucei deficientes em ISP1 (Δisp1), ISP2 (Δisp2) e em ambos os ISPs (Δisp1/2) foram produzidas com sucesso e a ausência dos inibidores comprovada com o uso de anticorpos monoclonais específicos contra o ISP1 e o ISP2, que reconhecem a proteina alvo em extractos de proteína total de parasitas selvagens mas não em extractos de parasitas mutantes. O efeito da ausência dos ISPs nas células foi avaliado in vitro e in vivo, verificando-se que a delecção individual de cada ISP não produz qualquer efeito nos parasitas que revelam um crescimento normal em cultura e padrões de infectividade em murganhos idênticos aos de parasitas selvagens. Em contraste, os parasitas Δisp1/2, embora possuam um crescimento normal in vitro com ausência de alterações morfológicas grosseiras, são caracterizados por um alteração na mobilidade e pela acumulação de micro-vesiculas na região da bolsa flagelar, consistente com um defeito no processo de endocitose/exocitose. Adicionalmente, por imunofluorescência foi possível localizar os ISPs no citoplasma e na perto da bolsa flagelar. Em conjunto, estes dados sugerem uma função intracelular, independente da actividade inibitória dos ISPs e provavelmente associada ao flagelo ou à bolsa flagelar. O papel biológico dos ISPs na interação parasita-hospedeiro foi também avaliada através da infecção de murganhos com os parasitas Δisp1/2.A monitorização da infecção demonstrou que a deleção de ambos os inibidores resulta em sobrevivência prolongada dos murganhos com cargas parasitárias reduzidas, sugerindo que os ISPs possuem um papel importante na sobrevivência do parasita. Em contraste com os resultados obtidos em Leishmania que atribuem diferentes funções a ISP1 e ISP2, este estudo sugere que existe uma redundância funcional dos mesmos em T. brucei, sendo necessária a presença de ambos para que o parasita estabeleça eficientemente a infecção no hospedeiro mamifero. Foram também realizados estudos de imuno-protecção em murganhos de modo a determinar o potencial dos ISPs como alvos terapêuticos. A imunização com ISP recombinante e o tratamento com anticorpos específicos contra ISP1 e ISP2 não produzem qualquer efeito protector ou neutralizante da infecção de murganhos, sugerindo que estes inibidores não constituem bons candidatos para o desenvolvimento de uma vacina ou terapia baseada em anticorpos.Peptidases are involved in several biological functions playing an important role in the pathogenicity of many parasitic infections. In mammals, one way in which the activity of these peptidases is controlledisby interaction with natural inhibitors, such as cystatins and serpins. In trypanosomatids, the genes encoding forendogenousinhibitors homologous to mammalian cystatins and serpins, are absent. Ecotin is an Escherichia coliprotein capable of inhibiting a wide range of serine peptidases from S1A family such as trypsin. Ecotin orthologues can be found in a restricted range of bacterial pathogens and also in trypanosomatid parasitic protozoa.In Trypanosomabruceitwo proteins of 19.7 kDa and 17.8 kDa were identified as ecotin-like inhibitors and given the generic name of Inhibitors of Serine Peptidases (ISP). The absence of peptidases predicted to be sensitive to the action of ISPs in T. bruceisuggests that these inhibitors are targeting the host’s serine peptidases, although their exact biological role was unknown. T. bruceimutant cell linesdeficientin ISP1 (Δisp1),ISP2 (Δisp2) and both ISPs (Δisp1/2) weresuccessfully generatedby targeted gene disruption. This was confirmed using monoclonal antibodies generated specifically against ISP1 and ISP2 that recognize the target protein in wild type and re-expressor cell lysates but not in the respective mutant cell line. Theeffect of ISP deletion in the parasiteswasdeterminedboth in culture andin micein vivo. The deletion of ISPgenes individually was shown to have no effect on the parasites in vitroor in vivo. However, different results were obtained for the simultaneous deletion of ISP1and ISP2. Although Δisp1/2parasites have normal growth and morphology in culture, they exhibit a motility defect and are characterized by the accumulation of small vesicles outside the flagellar pocket consistent with an endocytosis/exocytosis defect. Furthermore, immunofluorescence shows that both ISPs are localized in the cytosol and in small punctuated structures near the flagellar pocket region. These data suggests that ISPs have an intracellular function independent of their inhibitory activityand probably associated with the flagellar pocket.The biological role of ISP1 and ISP2 in the host-parasite interaction was also evaluated by infecting mice with Δisp1/2parasites. Parasitemia monitoring shows that the deletion of both ISPsresults in prolonged host survival with reduced or undetectable parasite loads, suggesting an important role for these inhibitors in the parasite’s survival. In contrast with recent findings of ISPs functionin Leishmania, that assigns different biological roles to ISP1 and ISP2, the present study reveals some functional redundancy of ISPs in T. brucei,with both inhibitors being required for the parasite to infect the mammalian host efficiently. Finally, immuno-protection studies were made, to assess the potential of ISPs as targets for therapy. Immunization with recombinant ISPs and treatment with antibodies specific against ISP1 and ISP2 had no protective or neutralizing effecton T. bruceiinfected mice, revealing that these inhibitors are poor candidates for an anti-disease vaccine or for antibody-based therapy
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
- …
