Mythologies de l'après vache-folle, relecture de Roland Barthes

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Response to Treatment and Disease Progression Linked to CD4+ T Cell Surface CC Chemokine Receptor 5 Density in Human Immunodeficiency Virus Type 1 Vertical Infection

The factors governing interindividual variability in disease progression among children vertically infected with human immunodeficiency virus type 1 (HIV-1) remain unclear. Because it has recently been shown in infected adults that the density of CC chemokine receptor 5 (CCR5) molecules at the surface of nonactivated (human leukocyte antigen [HLA]-DR-) CD4+ T cells correlates with disease progression, the same correlation was sought in children. HLA-DR-CD4+ T cell surface CCR5 density was constant over time and correlated with the bioclinical stage and with the CD4 cell slope observed before antiretroviral treatment. In addition, CCR5 density was negatively correlated with the intensity of the decrease in viremia during antiretroviral therapy and was positively correlated with CD4 cell slope since birth. These results are compatible with the hypothesis that CCR5 density is a key factor governing disease progression in pediatric HIV-1 infection and, thereby, an indicator of prognosis. Moreover, they suggest that therapies aimed at reducing CCR5 accessibility should slow down HIV disease evolution in childre

T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID

BackgroundAs about 10% of patients with COVID-19 present sequelae, it is important to better understand the physiopathology of so-called long COVID.MethodTo this aim, we recruited 29 patients hospitalized for SARS-CoV-2 infection and, by Luminex®, quantified 19 soluble factors in their plasma and in the supernatant of their peripheral blood mononuclear cells, including inflammatory and anti-inflammatory cytokines and chemokines, Th1/Th2/Th17 cytokines, and endothelium activation markers. We also measured their T4, T8 and NK differentiation, activation, exhaustion and senescence, T cell apoptosis, and monocyte subpopulations by flow cytometry. We compared these markers between participants who developed long COVID or not one year later.ResultsNone of these markers was predictive for sequelae, except programmed T4 cell death. T4 lymphocytes from participants who later presented long COVID were more apoptotic in culture than those of sequelae-free participants at Month 12 (36.9 ± 14.7 vs. 24.2 ± 9.0%, p = 0.016).ConclusionsOur observation raises the hypothesis that T4 cell death during the acute phase of SARS-CoV-2 infection might pave the way for long COVID. Mechanistically, T4 lymphopenia might favor phenomena that could cause sequelae, including SARS-CoV-2 persistence, reactivation of other viruses, autoimmunity and immune dysregulation. In this scenario, inhibiting T cell apoptosis, for instance, by caspase inhibitors, could prevent long COVID

Small-Molecule Inhibition of HIV pre-mRNA Splicing as a Novel Antiretroviral Therapy to Overcome Drug Resistance

The development of multidrug-resistant viruses compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, it is an ongoing task to identify new targets for antiretroviral therapy and to develop new drugs. Here, we show that an indole derivative (IDC16) that interferes with exonic splicing enhancer activity of the SR protein splicing factor SF2/ASF suppresses the production of key viral proteins, thereby compromising subsequent synthesis of full-length HIV-1 pre-mRNA and assembly of infectious particles. IDC16 inhibits replication of macrophage- and T cell–tropic laboratory strains, clinical isolates, and strains with high-level resistance to inhibitors of viral protease and reverse transcriptase. Importantly, drug treatment of primary blood cells did not alter splicing profiles of endogenous genes involved in cell cycle transition and apoptosis. Thus, human splicing factors represent novel and promising drug targets for the development of antiretroviral therapies, particularly for the inhibition of multidrug-resistant viruses

Combined Phytochemistry and Chemotaxis Assays for Identification and Mechanistic Analysis of Anti-Inflammatory Phytochemicals in Fallopia japonica

Plants provide a rich source of lead compounds for a variety of diseases. A novel approach combining phytochemistry and chemotaxis assays was developed and used to identify and study the mechanisms of action of the active compounds in F. japonica, a medicinal herb traditionally used to treat inflammation. Based on a bioactivity-guided purification strategy, two anthranoids, emodin and physcion, were identified from F. japonica. Spectroscopic techniques were used to characterize its crude extract, fractions and phytochemicals. The crude extract, chloroform fraction, and anthranoids of F. japonica significantly inhibited CXCR4-mediated chemotaxis. Mechanistic studies showed that emodin and physcion inhibited chemotaxis via inactivating the MEK/ERK pathway. Moreover, the crude extract and emodin could prevent or treat type 1 diabetes in non-obese diabetic (NOD) mice. This study illustrates the applicability of a combinational approach for the study of anti-inflammatory medicine and shows the potential of F. japonica and its anthranoids for anti-inflammatory therapy

Effective Gene Therapy in a Mouse Model of Prion Diseases

Classical drug therapies against prion diseases have encountered serious difficulties. It has become urgent to develop radically different therapeutic strategies. Previously, we showed that VSV-G pseudotyped FIV derived vectors carrying dominant negative mutants of the PrP gene are efficient to inhibit prion replication in chronically prion-infected cells. Besides, they can transduce neurons and cells of the lymphoreticular system, highlighting their potential use in gene therapy approaches. Here, we used lentiviral gene transfer to deliver PrPQ167R virions possessing anti-prion properties to analyse their efficiency in vivo. Since treatment for prion diseases is initiated belatedly in human patients, we focused on the development of a curative therapeutic protocol targeting the late stage of the disease, either at 35 or 105 days post-infection (d.p.i.) with prions. We observed a prolongation in the lifespan of the treated mice that prompted us to develop a system of cannula implantation into the brain of prion-infected mice. Chronic injections of PrPQ167R virions were done at 80 and 95 d.p.i. After only two injections, survival of the treated mice was extended by 30 days (20%), accompanied by substantial improvement in behaviour. This delay was correlated with: (i) a strong reduction of spongiosis in the ipsilateral side of the brain by comparison with the contralateral side; and (ii) a remarkable decrease in astrocytic gliosis in the whole brain. These results suggest that chronic injections of dominant negative lentiviral vectors into the brain, may be a promising approach for a curative treatment of prion diseases

Interfering RNA and HIV: Reciprocal Interferences

In this review, a quick presentation of what interfering RNA (iRNA) are—small RNA able to exert an inhibition on gene expression at a posttranscriptional level, based on sequence homology between the iRNA and the mRNA—will be given. The many faces of the interrelations between iRNA and viruses, particularly HIV, will be reviewed. Four kinds of interactions have been described: i) iRNA of viral origin blocking viral RNA, ii) iRNA of viral origin downregulating cellular mRNA, iii) iRNA of cellular origin (microRNA) targeting viral RNA, and iv) microRNA downregulating cellular mRNA encoding cell proteins used by the virus for its replication. Next, HIV strategies to manipulate these interrelations will be considered: suppression of iRNA biosynthesis by Tat, trapping by the HIV TAR sequence of a cell component, TRBP, necessary for iRNA production and action, and induction by the virus of some microRNA together with suppression of others. Then, we will discuss the putative effects of these mutual influences on viral replication as well as on viral latency, immune response, and viral cytopathogenicity. Finally, the potential consequences on the human infection of genetic polymorphisms in microRNA genes and the therapeutic potential of iRNA will be presented

: Cuisine, alimentation, Métissages

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Cuisiner, pâtisser, métisser

Kochen, Backen, Mischen. Kochen und essen gehören in den von uns so bezeichneten «Bereich der Nahrung». Wir gehen davon aus, dass sie, die zu unserer Identitätsbildung beiträgt, auch von einer beständigen Anomie gekennzeichnet ist, die zweifellos zu bestimmten Zeiten ausgeprägter oder dra¬ matisierter erscheint. Der Koch/Konsument muss also in bestimmten Situationen eine Wahl treffen oder ertragen, um diesen oder jenen seiner Wünsche zu entsprechen. Diese Rekonstruktion, die bei der betroffenen Person Zentripetal-und Zentrifugalkräfte vermischt, spielt sich in fünf Szenarien ab... wo man ein mystifiziertes gastronomisches Erbe valorisiert, das als christallisiert empfunden wird (diese Pseudoreproduktion endet für uns in verschiedenen Mutationsformen), es sei denn, man schliesst sich in einer Neophobie ein, die von einer Schulhypothese zeugt. Man kann sich auch in geschmacklichen Mischungen wieder zusammenfügen. Wir schlagen dazu drei Formen vor : die auf gezwungene Mischung, die erwünschte Mischung sowie die unerwartete Mischung. Wir betonen, dass jenseits der geschmacklichen Mutationen das Auftauchen einer Umkehrung der verschiedenen Arten der alltäglichen Küche und in der «grande cuisine» zu einer anderen Art von erwünschter Mischung führt.Cooking, baking, mixing. Cooking and eating are part of what we call the «business of eating». We would say that this is part of the making of our identity, is also characterised by an eternal anomie, certainly more important or dramatised at any given time. Then, the cook/eater must make or be suggested to choices in certain situations so as to fulfil one or the other of his wishes. This reconstruction that involves both centripetal and centrifugal forces in the actor takes place in five scenarios. You enhance the value of a mythicised gastronomic heritage, which is regarded as being crystallised, (for us, this pseudo reproduction results in various types of changes) unless locking yourself into a neophobia which is only a hypothetical case. It is also possible to reconstruct oneself through a blend of taste experiences. Imposed crossing, desired crossing and unthought-of crossing are three types of them. We would stress that beyond gustative changes, the emergence of styles’ inversion in daily cooking and in «cuisine» leads to another type of desired crossing.Corbeau Jean-Pierre. Cuisiner, pâtisser, métisser. In: Revue des sciences sociales, N°27, 2000. Révolution dans les cuisines. pp. 68-73