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Ixodes ricinus Tick Lipocalins: Identification, Cloning, Phylogenetic Analysis and Biochemical Characterization
Jér?me Beaufays, Beno?t Adam, Yves Decrem, Pierre-Paul Prévt, Sébastien Santini, Robert Brasseur, Michel Brossard, Laurence Lins, Luc Vanhamme, Edmond Godfroid
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003941
Abstract: Background During their blood meal, ticks secrete a wide variety of proteins that interfere with their host's defense mechanisms. Among these proteins, lipocalins play a major role in the modulation of the inflammatory response. Methodology/Principal Findings Screening a cDNA library in association with RT-PCR and RACE methodologies allowed us to identify 14 new lipocalin genes in the salivary glands of the Ixodes ricinus hard tick. A computational in-depth structural analysis confirmed that LIRs belong to the lipocalin family. These proteins were called LIR for “Lipocalin from I. ricinus” and numbered from 1 to 14 (LIR1 to LIR14). According to their percentage identity/similarity, LIR proteins may be assigned to 6 distinct phylogenetic groups. The mature proteins have calculated pM and pI varying from 21.8 kDa to 37.2 kDa and from 4.45 to 9.57 respectively. In a western blot analysis, all recombinant LIRs appeared as a series of thin bands at 50–70 kDa, suggesting extensive glycosylation, which was experimentally confirmed by treatment with N-glycosidase F. In addition, the in vivo expression analysis of LIRs in I. ricinus, examined by RT-PCR, showed homogeneous expression profiles for certain phylogenetic groups and relatively heterogeneous profiles for other groups. Finally, we demonstrated that LIR6 codes for a protein that specifically binds leukotriene B4. Conclusions/Significance This work confirms that, regarding their biochemical properties, expression profile, and sequence signature, lipocalins in Ixodes hard tick genus, and more specifically in the Ixodes ricinus species, are segregated into distinct phylogenetic groups suggesting potential distinct function. This was particularly demonstrated by the ability of LIR6 to scavenge leukotriene B4. The other LIRs did not bind any of the ligands tested, such as 5-hydroxytryptamine, ADP, norepinephrine, platelet activating factor, prostaglandins D2 and E2, and finally leukotrienes B4 and C4.
Variability and Action Mechanism of a Family of Anticomplement Proteins in Ixodes ricinus
Bernard Couvreur, Jér?me Beaufays, Cédric Charon, Kathia Lahaye, Fran?ois Gensale, Valérie Denis, Beno?t Charloteaux, Yves Decrem, Pierre-Paul Prévt, Michel Brossard, Luc Vanhamme, Edmond Godfroid
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0001400
Abstract: Background Ticks are blood feeding arachnids that characteristically take a long blood meal. They must therefore counteract host defence mechanisms such as hemostasis, inflammation and the immune response. This is achieved by expressing batteries of salivary proteins coded by multigene families. Methodology/Principal Findings We report the in-depth analysis of a tick multigene family and describe five new anticomplement proteins in Ixodes ricinus. Compared to previously described Ixodes anticomplement proteins, these segregated into a new phylogenetic group or subfamily. These proteins have a novel action mechanism as they specifically bind to properdin, leading to the inhibition of C3 convertase and the alternative complement pathway. An excess of non-synonymous over synonymous changes indicated that coding sequences had undergone diversifying selection. Diversification was not associated with structural, biochemical or functional diversity, adaptation to host species or stage specificity but rather to differences in antigenicity. Conclusions/Significance Anticomplement proteins from I. ricinus are the first inhibitors that specifically target a positive regulator of complement, properdin. They may provide new tools for the investigation of role of properdin in physiological and pathophysiological mechanisms. They may also be useful in disorders affecting the alternative complement pathway. Looking for and detecting the different selection pressures involved will help in understanding the evolution of multigene families and hematophagy in arthropods.
Ir-LBP, an Ixodes ricinus Tick Salivary LTB4-Binding Lipocalin, Interferes with Host Neutrophil Function
Jér?me Beaufays, Beno?t Adam, Catherine Menten-Dedoyart, Laurence Fievez, Amélie Grosjean, Yves Decrem, Pierre-Paul Prévt, Sébastien Santini, Robert Brasseur, Michel Brossard, Michel Vanhaeverbeek, Fabrice Bureau, Ernst Heinen, Laurence Lins, Luc Vanhamme, Edmond Godfroid
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003987
Abstract: Background During their blood meal, ticks secrete a wide variety of proteins that can interfere with their host's defense mechanisms. Among these proteins, lipocalins play a major role in the modulation of the inflammatory response. Methodology/Principal Findings We previously identified 14 new lipocalin genes in the tick Ixodes ricinus. One of them codes for a protein that specifically binds leukotriene B4 with a very high affinity (Kd: ±1 nM), similar to that of the neutrophil transmembrane receptor BLT1. By in silico approaches, we modeled the 3D structure of the protein and the binding of LTB4 into the ligand pocket. This protein, called Ir-LBP, inhibits neutrophil chemotaxis in vitro and delays LTB4-induced apoptosis. Ir-LBP also inhibits the host inflammatory response in vivo by decreasing the number and activation of neutrophils located at the tick bite site. Thus, Ir-LBP participates in the tick's ability to interfere with proper neutrophil function in inflammation. Conclusions/Significance These elements suggest that Ir-LBP is a “scavenger” of LTB4, which, in combination with other factors, such as histamine-binding proteins or proteins inhibiting the classical or alternative complement pathways, permits the tick to properly manage its blood meal. Moreover, with regard to its properties, Ir-LBP could possibly be used as a therapeutic tool for illnesses associated with an increased LTB4 production.
Le modèle québécois : origines, définition, fondements et adaptation au nouveau contexte économique et social
Pierre-Paul Proulx
Interventions économiques , 2002,
Abstract: à partir de plusieurs écrits sur le modèle québécois et le Québec Inc., l’article montre que ces termes prennent plusieurs significations selon les auteurs. Ainsi, pour certains, ils traduisent un corporatiste, un véritable réseau ou un nationalisme économique ; pour d’autres, ils sont l’expression de la présence fran aise en Amérique du nord ou encore un modèle d’émancipation d’un peuple et d’entreprises francophones. Le modèle de développement émerge des grands acteurs socio-économiques de ces dernières soixante années et ses caractéristiques permettent de saisir la notion d’intérêt général comme étant l’expression d’une communauté de personnes et non d’un marché. Plus qu’un concept qui chapeaute une classe d’affaire, Québec Inc serait un véritable projet de société et l’expression d’un modèle de développement fondé sur une alliance particulière entre les pouvoirs économiques public et privé dont l’objectif a été et continu d’être la poursuite d’une politique de croissance par la prise en main des leviers économiques du Québec. Enfin, il n’est rien d’autre qu’un désir "naturel" de concertation dans un monde où le regroupement des forces et des intelligences s’impose. Mais pour un renouvellement du modèle, un partage d’objectifs de la part des acteurs impliqués s’avère important de même qu’une "recapitalisation" sociale. L’article se termine en soulignant l’importance de la concertation et de la solidarité comme du capital social dont un nouveau modèle québécois dans un contexte actuel ne peut en faire l’économie. From several papers on the Quebecois model and Quebec Inc ., the article shows that these terms take several meanings according to the authors. So, for some, they translate a corporatist, a real network or an economic nationalism; for others, they are the expression of the french presence in North America or another model of emancipation of people and french-speaking companies. The model of development appears from big socioeconomic actors of these last sixty years and its characteristics allow to seize the notion of general interest as being the expression of a community of persons and not of a market. More than a concept which heads a class of business, Quebec Inc. would be a real project of society and the expression of a model of development based on a particular alliance between the public and private economic powers the objective of which was and continuous to be the pursuit of a policy of growth by the grip in hand of the economic control levers of Quebec. Finally, it is nothing else than a "natural" desire of dialogue in a world where
La presse, la chute d’Adolfo Suárez et le 23-F (septembre 1980 – février 1981) La prensa, la caída de Adolfo Suárez y el 23-F
Pierre-Paul Grégorio
Cahiers de Civilisation Espagnole Contemporaine , 2009, DOI: 10.4000/ccec.2469
Abstract: Ce travail, présenté pour la HDR, analyse le discours de presse (sous ses différentes modalités) à partir de trois quotidiens madrilènes : ABC, Ya et El Alcázar. Il recouvre une période particulièrement tendue de l’histoire récente espagnole : celle du dernier gouvernement de l’ère Suárez, qui déboucha sur la tentative avortée du coup d’état du 23 février 1981.Entre septembre 1980 et février 1981, l’Espagne connut une crise politique grave dont les trois quotidiens se firent l’écho. Cependan...
Los inicios del cerco a Adolfo Suárez
Pierre-Paul Grégorio
Cahiers de Civilisation Espagnole Contemporaine , 2011, DOI: 10.4000/ccec.2559
Abstract: Se trata de poner en perspectiva la oposición creciente que Adolfo Suárez tuvo que arrostrar desde septiembre 1977 hasta septiembre de 1980, y que tuvo su origen en muy diversos sectores de las elites nacionales del momento. A través del encadenamiento de diferentes acontecimientos, sin duda inconexos entre sí en un primer tiempo, se va a ir creando en la Espa a de la Transición un sentimiento de hastío y de rechazo hacia el Presidente electo. El estudio se cierra en el momento de la formación del último gobierno liderado por Adolfo Suárez. En otras palabras, cuando esa cacería de la que hablaba Cándido , empezó a cobrar mayor amplitud. Por ello, a través de las líneas que siguen, intentamos trazar el panorama que condujo, precisamente, a ese proceso de desestabilización que acabaría, de manera no forzosamente deseada por algunos actores del mismo, en la intentona del 23-F. Y todo ello, empezando a se alar el papel que algunos periódicos –El Alcázar y, en mucho menor medida, Ya y ABC– pudieran haber tenido en tales premisas.
Shearer's inequality and Infimum Rule for Shannon entropy and topological entropy
Tomasz Downarowicz,Bartosz Frej,Pierre-Paul Romagnoli
Mathematics , 2015,
Abstract: We review subbadditivity properties of Shannon entropy, in particular, from the Shearer's inequality we derive the "infimum rule" for actions of amenable groups. We briefly discuss applicability of the "infimum formula" to actions of other groups. Then we pass to topological entropy of a cover. We prove Shearer's inequality for disjoint covers and give counterexamples otherwise. We also prove that, for actions of amenable groups, the supremum over all open covers of the "infimum fomula" gives correct value of topological entropy.
Ontogeny of Mouse Vestibulo-Ocular Reflex Following Genetic or Environmental Alteration of Gravity Sensing
Mathieu Beraneck, Mickael Bojados, Anne Le Séac’h, Marc Jamon, Pierre-Paul Vidal
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0040414
Abstract: The vestibular organs consist of complementary sensors: the semicircular canals detect rotations while the otoliths detect linear accelerations, including the constant pull of gravity. Several fundamental questions remain on how the vestibular system would develop and/or adapt to prolonged changes in gravity such as during long-term space journey. How do vestibular reflexes develop if the appropriate assembly of otoliths and semi-circular canals is perturbed? The aim of present work was to evaluate the role of gravity sensing during ontogeny of the vestibular system. In otoconia-deficient mice (ied), gravity cannot be sensed and therefore maculo-ocular reflexes (MOR) were absent. While canals-related reflexes were present, the ied deficit also led to the abnormal spatial tuning of the horizontal angular canal-related VOR. To identify putative otolith-related critical periods, normal C57Bl/6J mice were subjected to 2G hypergravity by chronic centrifugation during different periods of development or adulthood (Adult-HG) and compared to non-centrifuged (control) C57Bl/6J mice. Mice exposed to hypergravity during development had completely normal vestibulo-ocular reflexes 6 months after end of centrifugation. Adult-HG mice all displayed major abnormalities in maculo-ocular reflexe one month after return to normal gravity. During the next 5 months, adaptation to normal gravity occurred in half of the individuals. In summary, genetic suppression of gravity sensing indicated that otolith-related signals might be necessary to ensure proper functioning of canal-related vestibular reflexes. On the other hand, exposure to hypergravity during development was not sufficient to modify durably motor behaviour. Hence, 2G centrifugation during development revealed no otolith-specific critical period.
Proteomic Analysis of Excretory-Secretory Products of Heligmosomoides polygyrus Assessed with Next-Generation Sequencing Transcriptomic Information
Yovany Moreno,Pierre-Paul Gros,Mifong Tam,Mariela Segura,Rajesh Valanparambil,Timothy G. Geary,Mary M. Stevenson
PLOS Neglected Tropical Diseases , 2011, DOI: 10.1371/journal.pntd.0001370
Abstract: The murine parasite Heligmosomoides polygyrus is a convenient experimental model to study immune responses and pathology associated with gastrointestinal nematode infections. The excretory-secretory products (ESP) produced by this parasite have potent immunomodulatory activity, but the protein(s) responsible has not been defined. Identification of the protein composition of ESP derived from H. polygyrus and other relevant nematode species has been hampered by the lack of genomic sequence information required for proteomic analysis based on database searches. To overcome this, a transcriptome next generation sequencing (RNA-seq) de novo assembly containing 33,641 transcripts was generated, annotated, and used to interrogate mass spectrometry (MS) data derived from 1D-SDS PAGE and LC-MS/MS analysis of ESP. Using the database generated from the 6 open reading frames deduced from the RNA-seq assembly and conventional identification programs, 209 proteins were identified in ESP including homologues of vitellogenins, retinol- and fatty acid-binding proteins, globins, and the allergen V5/Tpx-1-related family of proteins. Several potential immunomodulators, such as macrophage migration inhibitory factor, cysteine protease inhibitors, galectins, C-type lectins, peroxiredoxin, and glutathione S-transferase, were also identified. Comparative analysis of protein annotations based on the RNA-seq assembly and proteomics revealed processes and proteins that may contribute to the functional specialization of ESP, including proteins involved in signalling pathways and in nutrient transport and/or uptake. Together, these findings provide important information that will help to illuminate molecular, biochemical, and in particular immunomodulatory aspects of host-H. polygyrus biology. In addition, the methods and analyses presented here are applicable to study biochemical and molecular aspects of the host-parasite relationship in species for which sequence information is not available.
Will an Unsupervised Self-Testing Strategy Be Feasible to Operationalize in Canada? Results from a Pilot Study in Students of a Large Canadian University
Nitika Pant Pai,Madhavi Bhargava,Lawrence Joseph,Jigyasa Sharma,Sabrina Pillay,Bhairavi Balram,Pierre-Paul Tellier
AIDS Research and Treatment , 2014, DOI: 10.1155/2014/747619
Abstract: Background. A convenient, private, and accessible HIV self-testing strategy stands to complement facility-based conventional testing. Over-the-counter oral HIV self-tests are approved and available in the United States, but not yet in Canada. Canadian data on self-testing is nonexistent. We investigated the feasibility of offering an unsupervised self-testing strategy to Canadian students. Methods. Between September 2011 and May 2012, we recruited 145 students from a student health clinic of a large Canadian university. Feasibility of operationalization (i.e., self-test conduct, acceptability, convenience, and willingness to pay) was evaluated. Self-test conduct was computed with agreement between the self-test performed by the student and the test repeated by a healthcare professional. Other metrics were measured on a survey. Results. Participants were young (median age: 22 years), unmarried (97%), and 47% were out of province or international students. Approximately 52% self-reported a history of unprotected casual sex and sex with multiple partners. Self-test conduct agreement was high (100%), so were acceptability (81%), convenience (99%), and willingness to pay (74%) for self-tests. Concerns included accuracy of self-tests and availability of expedited linkages. Conclusion. An unsupervised self-testing strategy was found to be feasible in Canadian students. Findings call for studies in at-risk populations to inform Canadian policy. 1. Introduction At the end of 2008, an estimated 65,000 Canadians were living with HIV, an increase of 14% since 2005 [1]. About 2,300 to 4,300 new HIV infections occurred in 2008 alone. Despite the availability of facility-based HIV testing and counselling [2], approximately 26% of all positive Canadians remain unaware of their HIV serostatus [1]. Systemic and social barriers, such as stigma, perceived discrimination, and the fear of social visibility and lack of confidentiality have long deterred uptake of conventional facility-based testing. In addition, fear of the test result and the belief that they are not at risk can also prevent some individuals from accessing testing. Furthermore, an increased anxiety associated with long wait times to receive test results and loss of work days associated with getting an HIV test have further impeded the uptake of facility-based HIV testing [3–9]. Conventional testing at a healthcare facility in Canada can be (a) nominal (i.e., the name of the person being tested appears on test forms, results, and medical records), (b) nonnominal (i.e., the test is ordered using a code, but
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