168 research outputs found

    Proteomic analysis of inflammatory protein expression patterns in cell culture and transgenic animal models for Alzheimer's disease

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    Dementia is a syndrome characterized by failure of recent memory and other cognitive functions that is usually insidious in onset but steadily progresses with age. Alzheimer’s disease (AD) is the most common form of senile dementia. It is neuropathologically characterized by extracellular and perivascular aggregation of amyloid β (Aβ) peptide, by the generation of intracellular neurofibrillary tangles due to a hyperphosphorylation of tau protein and by an increased rate of neuronal degeneration. The degenerative process starts 20-30 years before the clinical onset of the disease. Clinical diagnosis of AD is difficult but possible, but can only be confirmed by biopsy or autopsy. At present, no biological marker exists for early diagnosis of AD during life. Therefore, identification of biomarkers for AD would be of great value for clinical diagnosis of incipient AD. Recent studies have proven the involvement of inflammatory processes in the neurodegenerative events in AD. Inflammation may not be the first event in the progression of the disease, but it involves activation of glia cells including microglia and astrocytes and subsequent release of proinflammatory mediators. Cytokines released such as IL-1, TNF-α and IL-6 are the main proinflammatory cytokines that can modulate inflammatory responses as well as glial proliferation and activation. Oxidative stress triggered by inflammatory processes causes changes in proteins such as tyrosine nitration or lipid peroxidation. Aβ deposits, tau hyperphosphorylation, inflammation and oxidative stress may finally lead to changes in synaptic connectivity and efficacy including perturbation of long-term potentiation (LTP), important in the formation of memory. Proteomic technology used in these studies is a recent technology which is a two step process: separation of proteins and their subsequent analysis by mass spectrometry. Moreover, this technology can provide new information concerning the expression level, post-translational modification of specific proteins as well as their conformational changes during disease progression. In our study, this technology was modified and improved, e.g by the miniaturization of the complete process. Proteomic technology was also used in parallel with other methods such as chromatography in order to increase the sensitivity of detection by mass spectrometry. This study aimed: 1) To establish that cytokine treatment of human microglia cells is an efficient method to study certain aspects of AD pathogenesis. For this analysis, a map of protein expression in normal and in treated microglia cells was made. 2) To map protein expression in APP/PS2 transgenic mice, a model for human AD, in order to compare human AD brain with murine models. 3) To identify highly nitrated proteins in brains of transgenic animals. Several proteins were found to be modified after injury. 4) To provide evidence for instability of synapses in AD brains. To start with this study, the technologies used to map mouse brain cytosolic proteins were improved. 5) To isolate synaptosomal membranes from the whole brain and to analyse it by massspectrometry. For mapping synaptic membrane protein expression in controls or transgenic mouse models, the technology was miniaturizated and optimized. This study is still in progress

    Retraction Note to: Omega-3 fatty acid levels in red blood cell membranes and physical decline over 3 years: longitudinal data from the MAPT study

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    International audienceThe Editors-in-Chief have retracted this articlebecause it contains text in the introduction and dis-cussion sections that overlaps with a previous pub-lished article by a different author group [1]. BertrandFougere, Christelle Cantet, Gaelle Soriano, SophieGuyonnet, Philipe De Souto Barreto, Matteo Cesari,Sandrine Andrieu and Bruno Vellas agree with thisretraction. Bertrand Fougere agrees with this retrac-tion on behalf of the MAPT Study Group. SabineGossier has not responded to correspondence fromthe publisher about this retraction

    Les femmes, le genre et les sexualités dans le Maghreb colonial (1830-1962)

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    Dans cet article, Christelle Taraud revient sur trente ans d’histoire des femmes, du genre et des sexualités au Maghreb à l’époque coloniale (1830-1962). Mettant l’accent sur l’apport fondamental des gender, subaltern & colonial studies, l’article vise aussi à faire un bilan critique des avancées, et au contraire des absences et résistances dans un champ qui, au moins depuis les années 1970, est en voie de constitution. Au cœur de l’article, cinq grandes thématiques – colonisation, peuplement et femmes européennes ; femmes européennes et femmes « indigènes » : une rencontre coloniale ? ; l’orientalisme recontextualisé ; sexualités en situation coloniale ; et femmes, hommes et guerre en contexte colonial – permettent d’avoir une vision claire, quoique non exhaustive, de la production historiographique des années 1980-2010.The article examines thirty years in the history of women, gender and sexualities in colonial Maghreb (1830-1962). The author emphasizes the essential contribution of gender and subaltern & colonial studies, while also offering a critical review of the advances, as well as the silences and resistances within the field. Five themes structure the analysis of the historiographic production between 1980 and the present – colonization, settlement and European women ; relationships between European women and indigenous women ; recontexualised orientalism ; sexualities in a colonial context ; women, men and war in colonial situations

    The discovery of SycO reveals a new function for type three secretion effector chaperones

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    The Type Three Secretion (T3S) system is a device used by many Gram-negative pathogens that allows bacteria to deliver effector proteins straight into the eukaryotic cell cytosol. These effectors interfere with various signaling pathways to subvert the host cell functions. The secretion machinery of the T3S system consist of a basal body spanning the bacterial inner and outer membrane followed by a stiff hollow needle outside the bacterium. The fully assembled secretion apparatus constitute a continuous hollow conduit that connects the bacteria to the eukaryotic target cell. After cell contact, virulence proteins -called effectors- are injected directly into the cytosol of the host cell via the T3S apparatus. Several effectors of the T3S system require the assistance of specific cytosolic chaperones to be efficiently exported. There are three classes of T3S chaperones. Effector proteins are assisted by Class I chaperones. Although Class I chaperones are well characterized, their main function is still a matter of controversy. In this thesis, we demonstrate that orf155 encodes a specific chaperone for the effector YopO that we called SycO. We showed that SycO enhances YopO secretion in vitro and is required for translocation of YopO into infected cells. By pulldown assay we demonstrated that residues 20 to 77 of YopO are required and sufficient for SycO binding. Using crosslinking experiments and size exclusion chromatography analysis, we determined the stoichiometry of purified SycO and YopO-SycO complexes. SycO alone forms dimers in solution and the YopO-SycO complex has a 1:2 stoichiometry. These results suggested that SycO is a typical chaperone of the Class I. YopO is a serine/theronine kinase that interacts with Rho and Rac and disrupts the cytoskeleton of the target cells. YopO has been shown to localize at the cell plasma-membrane. By transfection of YopO-EGFP hybrid proteins into HEK293T cells, we demonstrated that the chaperone-binding domain (CBD) coincides with the membrane localization domain of YopO. Nevertheless, the CBD was not needed for the kinase activity of YopO. By ultracentrifugation, we also showed that the CBD causes YopO aggregation in the bacteria, when SycO does not cover it. Further, we show that the CBD of YopE and YopT also caused aggregation in the bacteria in the absence of SycE and SycT respectively. YopE, YopT and T3S effectors in other systems also act at the membrane of the eukaryotic host cell. We propose a new hypothesis concerning the role of T3S chaperones. The sub-cellular localization domain of effectors is aggregation-prone and creates the need for a chaperone inside bacteria. We propose that masking such aggregation-prone localization domains may be a general function for type III effector chaperones

    ナイジェリア南東部および中南部におけるラッサウイルス検出のためのRT-LAMPアッセイの開発

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    Lassa virus (LASV) causes Lassa fever (LF), a viral hemorrhagic fever endemic in West Africa. LASV strains are clustered into six lineages according to their geographic location. To confirm a diagnosis of LF, a laboratory test is required. Here, a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay using a portable device for the detection of LASV in southeast and south-central Nigeria using three primer sets specific for strains clustered in lineage II was developed. The assay detected in vitro transcribed LASV RNAs within 23 min and was further evaluated for detection in 73 plasma collected from suspected LF patients admitted into two health settings in southern Nigeria. The clinical evaluation using the conventional RT-PCR as the reference test revealed a sensitivity of 50% in general with 100% for samples with a viral titer of 9500 genome equivalent copies (geq)/mL and higher. The detection limit was estimated to be 4214 geq/mL. The assay showed 98% specificity with no cross-reactivity to other viruses which cause similar symptoms. These results suggest that this RT-LAMP assay is a useful molecular diagnostic test for LF during the acute phase, contributing to early patient management, while using a convenient device for field deployment and in resource-poor settings.長崎大学学位論文 学位記番号:博(医歯薬)甲第1265号 学位授与年月日:令和2年9月18日Author: Christelle M. Pemba, Yohei Kurosaki, Rokusuke Yoshikawa, Olamide K. Oloniniyi, Shuzo Urata, Maki Sueyoshi, Vahid R. Zadeh, Ifeanyi Nwafor, Michael O. Iroezindu, Nnenna A. Ajayi, Chinedu M. Chukwubike, Nneka M. Chika-Igwenyi, Anne C. Ndu, Damian U. Nwidi, Yuki Maehira, Uche S. Unigwe, Chiedozie K. Ojide, Emeka O. Onwe, Jiro YasudaCitation: Journal of Virological Methods, 269, pp.30-37; 201

    Irish Self-Portraits: The Artist in Curved Mirrors

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    International audienceThough Ireland can pride itself on its national self-portrait collection, housed at the University of Limerick, very little research has been done on self-portrayal in Irish literature and visual arts. This absence of scientific investigation is all the more surprising as, as Marie Bourke observes, “self-portrayal is a complex act. The private nature of the task, and the intensity of self-scrutiny that it entails, has challenged artists through the ages. It’s not just a question of self-examination, but a process recording a likeness, the depiction of a psychological state, or social status, or the representation of abstract ideas” (Marie Bourke, Exploring Art at the National Gallery, Dublin, National Gallery of Ireland, 1997, p. 35). Self-portraiture admittedly is a probing endeavor but cannot be a straightforward representation since it requires the use of a mirror. A dim light, expressive eyes or a focus on the face may be the hallmarks of a confession. But there is much more to a self-portrait than meets the eye –be it the eye of the artist him/herself or the viewer’s or the reader’s: “The conception of the self-portrait as a privileged insight into an authentic truth has, like all interpretation, been opened up to more demanding and nuanced scrutiny,” William Gallagher notes (Introduction to William Gallagher, The National Self-Portrait Collection of Ireland, volume 2 1989-1999, University of Limerick Press, 2006). If “a self-portrait is a purely personal commitment” inviting readers or viewers to “witness an intimate discovery” (Preface to Sarah Finlay, The National Self-Portrait Collection of Ireland, volume 1 1979-1989, University of Limerick Press, 1989, p. 10), such an image is not to be blindly trusted. Artists stage their own identities and persona, playing with fame and the artist’s personableness, showing disrespect, or disregarding conventions and mores. The mirror in which the artist beholds him/herself is therefore often a curved one. This volume of Études Irlandaises (Volume 43.1) seeks to scrutinize the diverging strategies that lie at the core of self-portraiture.Together with an introduction by Fintan Cullen, author of The Irish Face. Redefining the Irish Portrait (London, National Portrait Gallery, 2004), Volume 43.1 includes chapters on Samuel Beckett, Derek Mahon, Paul Durcan, Paul Muldoon, eighteenth-century self-portraiture, Erskine Nicol, Seán Keating, Amanda Coogan and Helena Walsh

    About Bullshit Jobs, Tribute to David Graeber. A podcast in three episodes: A podcast in three episodes.

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    Manifet, C. 2022. A propos des Jobs à la Con, Hommage à David Graeber, Une émission sonore en trois épisodes (Épisode 1(27mn), Épisode 2 (23mn), Épisode 3 (27mn), [https://www.canal-u.tv/chaines/ut2j/a-propos-des-jobs-ala-con-hommage-a-david-graeber-cala-con-hommage-a-david-graeber-]“David Graeber died suddenly on September 2, 2020. He was 59 years old. This podcast in three episodes (27 minutes, 23mn, and 27mn) aims to ward off this brutal death, by discussing his work, Bullshit Jobs, in French ‘Jobs à la Con’ (JAC), because it is a beautiful work of black humor! In this book, David Graeber argues that many of us have jobs that are inconsistent, useless, and even toxic to others and to ourselves. And, if our jobs are not bullshit jobs, they are still earned by bullshitization, that is to say that part of our tasks are bullshit jobs, unproductive, useless, even toxic . Bullshitization also evokes a growing phenomenon. Behind the subversive statement, the anthropologist carries a message of hope regarding the humanist rebuilding of our societies. He defends the interest of a universal income which would make it possible to disconnect work from remuneration and allow everyone to work less, to share work better, to gain freed up time for everyone, to think about what is really useful to produce in a society that would be more egalitarian and in accordance with its ecosystem. In this book, David Graeber puts us to the test: what if we had bullshit jobs? Are we able to laugh with him and laugh at ourselves? Are we able to consider recasting the rules of the social game? Let’s try: let’s listen to David Graeber [Christelle Manifet].” Episode 1: Presented here are the major questions that the anthropologist asked to identify his subject and objectify it in support of methods that are those of the social sciences: what are the generic attributes of Bullshit jobs? What are the external forms through which they manifest themselves? David Graeber distinguishes 5 main types of Bullshit Jobs.In the second episode and in support of the typology developed by the author, it is a question of asking ourselves if we are concerned: do we, ourselves, have Bullshit Jobs?The third and final episode is driven by the question of why? Why do Bullshit Jobs exist and proliferate? What is David Graeber's explanatory theory?Keywords: Anthropology -- Methodology; Professions; Value of work; Utility (economy); Labor Value, Theory of ; Social recognition; Job satisfaction; Personal -- Motivation; Sociology of workUne émission sonore en trois épisodes (Épisode 1(27mn), Épisode 2 (23mn), Épisode 3 (27mn). Pour écouter, c'est ici : https://www.canal-u.tv/chaines/ut2j/a-propos-des-jobs-ala-con-hommage-a-david-graeber-christelle-manifet Présentation « David Graeber est décédé brutalement le 2 septembre 2020. Il avait 59 ans. Cette émission vise à conjurer cette mort brutale, en traitant de son ouvrage, Bullshit Jobs, en français 'Jobs à la Con', parce que c'est une belle oeuvre d'humour noir

    About Bullshit Jobs, Tribute to David Graeber. A podcast in three episodes: A podcast in three episodes.

    No full text
    Manifet, C. 2022. A propos des Jobs à la Con, Hommage à David Graeber, Une émission sonore en trois épisodes (Épisode 1(27mn), Épisode 2 (23mn), Épisode 3 (27mn), [https://www.canal-u.tv/chaines/ut2j/a-propos-des-jobs-ala-con-hommage-a-david-graeber-cala-con-hommage-a-david-graeber-]“David Graeber died suddenly on September 2, 2020. He was 59 years old. This podcast in three episodes (27 minutes, 23mn, and 27mn) aims to ward off this brutal death, by discussing his work, Bullshit Jobs, in French ‘Jobs à la Con’ (JAC), because it is a beautiful work of black humor! In this book, David Graeber argues that many of us have jobs that are inconsistent, useless, and even toxic to others and to ourselves. And, if our jobs are not bullshit jobs, they are still earned by bullshitization, that is to say that part of our tasks are bullshit jobs, unproductive, useless, even toxic . Bullshitization also evokes a growing phenomenon. Behind the subversive statement, the anthropologist carries a message of hope regarding the humanist rebuilding of our societies. He defends the interest of a universal income which would make it possible to disconnect work from remuneration and allow everyone to work less, to share work better, to gain freed up time for everyone, to think about what is really useful to produce in a society that would be more egalitarian and in accordance with its ecosystem. In this book, David Graeber puts us to the test: what if we had bullshit jobs? Are we able to laugh with him and laugh at ourselves? Are we able to consider recasting the rules of the social game? Let’s try: let’s listen to David Graeber [Christelle Manifet].” Episode 1: Presented here are the major questions that the anthropologist asked to identify his subject and objectify it in support of methods that are those of the social sciences: what are the generic attributes of Bullshit jobs? What are the external forms through which they manifest themselves? David Graeber distinguishes 5 main types of Bullshit Jobs.In the second episode and in support of the typology developed by the author, it is a question of asking ourselves if we are concerned: do we, ourselves, have Bullshit Jobs?The third and final episode is driven by the question of why? Why do Bullshit Jobs exist and proliferate? What is David Graeber's explanatory theory?Keywords: Anthropology -- Methodology; Professions; Value of work; Utility (economy); Labor Value, Theory of ; Social recognition; Job satisfaction; Personal -- Motivation; Sociology of workUne émission sonore en trois épisodes (Épisode 1(27mn), Épisode 2 (23mn), Épisode 3 (27mn). Pour écouter, c'est ici : https://www.canal-u.tv/chaines/ut2j/a-propos-des-jobs-ala-con-hommage-a-david-graeber-christelle-manifet Présentation « David Graeber est décédé brutalement le 2 septembre 2020. Il avait 59 ans. Cette émission vise à conjurer cette mort brutale, en traitant de son ouvrage, Bullshit Jobs, en français 'Jobs à la Con', parce que c'est une belle oeuvre d'humour noir
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