T regulatory cells disrupt the CCL20-CCR6 axis driving Th17 homing to the gut

Background: During HIV-1 infection, the integrity of the intestinal immune barrier is disrupted due to a deep depletion of CD4 + T cells in the gut. The translocation of microbial products from the gut lumen into the bloodstream has been linked with systemic inflammation. Despite long-term effective cART, CD4 + T cells in the lamina propria are incompletely restored in most individuals. Aims: Among the chemotactic axes involved in CD4 + T cell homing to the gut, we focused on the CCR6-CCL20 axis as it governs Th17 cells homing, a T cell subset exerting a major role in antimicrobial immunity. We aimed to assess the factors regulating the expression of CCL20 by the enterocytes, and notably the role of the cytokines produced by Treg and Th17 cells. Methods: Small bowel biopsies were obtained by endoscopy in 20 HIV-1 + and 10 HIV-1-individuals. Intestinal lymphocytes phenotype was analyzed by flow cytometry. CCL20 mRNA was quantified by qRT-PCR. The effect of PRR ligands and cytokines on CCL20 expression was explored using an ex-vivosystem of human primary enterocytes. A coculture was done between the enterocytes and Th17/Treg cells. The expression of CCL20 by the enterocytes was evaluated by qRT-PCR and ELISA

Deciphering the Molecular Basis of Wine Yeast Fermentation Traits Using a Combined Genetic and Genomic Approach

The genetic basis of the phenotypic diversity of yeast is still poorly understood. Wine yeast strains have specific abilities to grow and ferment under stressful conditions compared with other strains, but the genetic basis underlying these traits is unknown. Understanding how sequence variation influences such phenotypes is a major challenge to address adaptation mechanisms of wine yeast. We aimed to identify the genetic basis of fermentation traits and gain insight into their relationships with variations in gene expression among yeast strains. We combined fermentation trait QTL mapping and expression profiling of fermenting cells in a segregating population from a cross between a wine yeast derivative and a laboratory strain. We report the identification of QTL for various fermentation traits (fermentation rates, nitrogen utilization, metabolites production) as well as expression QTL (eQTL). We found that many transcripts mapped to several eQTL hotspots and that two of them overlapped with QTL for fermentation traits. A QTL controlling the maximal fermentation rate and nitrogen utilization overlapping with an eQTL hotspot was dissected. We functionally demonstrated that an allele of the ABZ1 gene, localized in the hotspot and involved in p-aminobenzoate biosynthesis, controls the fermentation rate through modulation of nitrogen utilization. Our data suggest that the laboratory strain harbors a defective ABZ1 allele, which triggers strong metabolic and physiological alterations responsible for the generation of the eQTL hotspot. They also suggest that a number of gene expression differences result from some alleles that trigger major physiological disturbances

Blunted Response to Combination Antiretroviral Therapy in HIV Elite Controllers: An International HIV Controller Collaboration

Objective: HIV “elite controllers” (ECs) spontaneously control viral load, but some eventually require combination antiretroviral treatment (cART), due to a loss of viral control or a decline in CD4 T-cell counts. Here we studied the CD4 T-cell count dynamics after cART initiation among 34 ECs followed in U.S. and European cohorts, by comparison with chronically viremic patients (VIRs). Methods: ECs were defined as patients with at least ≥5 viral load (VL) measurements below 400 copies/mL during at least a 5-year period despite never receiving ART and were selected from the French ANRS CO18 cohort, the U.S. SCOPE cohort, the International HIV Controllers study and the European CASCADE collaboration. VIRs were selected from the ANRS COPANA cohort of recently-diagnosed (<1 year) ART-naïve HIV-1-infected adults. CD4 T-cell count dynamics after cART initiation in both groups were modelled with piecewise mixed linear models. Results: After cART initiation, CD4 T-cell counts showed a biphasic rise in VIRs with: an initial rapid increase during the first 3 months (+0.63/month), followed by +0.19/month. This first rapid phase was not observed in ECs, in whom the CD4Tc count increased steadily, at a rate similar to that of the second phase observed in VIRs. After cART initiation at a CD4 T-cell count of 300/mm3, the estimated mean CD4 T-cell gain during the first 12 months was 139/mm3 in VIRs and 80/mm3 in ECs (p = 0.048). Conclusions: cART increases CD4 T-cell counts in elite controllers, albeit less markedly than in other patients

HIV-1 Residual Viremia Correlates with Persistent T-Cell Activation in Poor Immunological Responders to Combination Antiretroviral Therapy

BACKGROUND:The clinical significance and cellular sources of residual human immunodeficiency virus type 1 (HIV-1) production despite suppressive combination antiretroviral therapy (cART) remain unclear and the effect of low-level viremia on T-cell homeostasis is still debated. METHODOLOGY/PRINCIPAL FINDINGS:We characterized the recently produced residual viruses in the plasma and short-lived blood monocytes of 23 patients with various immunological responses to sustained suppressive cART. We quantified the residual HIV-1 in the plasma below 50 copies/ml, and in the CD14(high) CD16(-) and CD16+ monocyte subsets sorted by flow cytometry, and predicted coreceptor usage by genotyping V3 env sequences. We detected residual viremia in the plasma of 8 of 10 patients with poor CD4+ T-cell reconstitution in response to cART and in only 5 of 13 patients with good CD4+ T-cell reconstitution. CXCR4-using viruses were frequent among the recently produced viruses in the plasma and in the main CD14(high) CD16(-) monocyte subset. Finally, the residual viremia was correlated with persistent CD4+ and CD8+ T-cell activation in patients with poor immune reconstitution. CONCLUSIONS:Low-level viremia could result from the release of archived viruses from cellular reservoirs and/or from ongoing virus replication in some patients. The compartmentalization of the viruses between the plasma and the blood monocytes suggests at least two origins of residual virus production during effective cART. CXCR4-using viruses might be produced preferentially in patients on cART. Our results also suggest that low-level HIV-1 production in some patients may contribute to persistent immune dysfunction despite cART

Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis

<p>Abstract</p> <p>Background</p> <p>Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool.</p> <p>Methods</p> <p>We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3).</p> <p>Results</p> <p>Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel.</p> <p>Conclusions</p> <p>Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.</p

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Bases d'une lutte physique contre la bruche de l'arachide : étude de la résistance thermique : rapport de stage de seconde année

La bruche de l'arachide (#Caryedon serratus$ Ol.), principal ravageur des stocks de cette plante doit être détruite avant la mise en grenier. Une méthode physique de lutte adaptée aux conditions locales, la solarisation, paraît être un moyen envisageable. La présente étude vise à en démontrer la faisabilité. Ce travail consiste en la détermination des stades utilisables, des critères de mortalité afin d'établir l'évolution des TL50 et TL90 en fonction de la température à laquelle sont exposés les insectes dans une étuve. Le stade le plus résistant est la nymphe dans son cocon (jusqu'à 65°C durant plusieurs minutes). Le procédé de solarisation qui permet d'atteindre des températures supérieures est donc applicable. Il reste à en déterminer les conditions pratiques d'application. (Résumé d'auteur

Affinités phylogénétiques d'une nouvelle espèce de bruche ravageuse de Cercis siliquastrum L. en Chine et en Europe (Coleoptera: Chrysomelidae: Bruchinae: Bruchini)

Correspondance: [email protected], [email protected], [email protected] audienceBruchidius siliquastri n. sp. is described. This seed-beetle develops in pods of Cercis siliquastrum, a widely grown ornamental tree. Several recent reports reveal that this species is well established in Southern France. The presence of this species is also reported from Hungary. The relationships of this new species are investigated using both morphological data and molecular phylogenetic analyses. Our results indicate that this species is likely related to a mostly Paleotropical group, which includes members of genera Bruchidius and Conicobruchus. Hypotheses on the geographic origin of this new species are also discussedBruchidius siliquastri n. sp. est décrite. Cette bruche se développe dans les gousses de Cercis siliquastrum, un arbre ornemental qui est fréquemment planté à travers le monde. Des observations récentes révèlent que cette espèce est bien installée dans le sud de la France. La présence de cette espèce en Hongrie est également rapportée. Les liens de parenté de cette nouvelle espèce sont examinés à l’aide de données morphologiques et d’analyses phylogénétiques basées sur des caractères moléculaires. Nos résultats indiquent que cette espèce est vraisemblablement apparentée à un groupe majoritairement paléotropical, qui inclut des membres des genres Bruchidius et Conicobruchus. Des hypothèses concernant l’origine géographique de cette nouvelle espèce sont également discutées

Détection de virus minoritaire au sein des quasi-espèces du HIV-1 (application à l'étude de la mutation de résistance K103N)

La faible sensibilité de détection des virus minoritaires au sein des quasi-espèces du VHI-1 est un des facteurs limitants principaux des tests de résistance actuellement utilisés en pratique clinique. Nous avons développé une technique de PCR allèle-spécifique en temps réel capable de quantifier des virus minoritaires porteurs de la mutation K103N associée à la résistance aux inhibiteurs non-nucléosidiques de la transcriptase inverse jusqu'à une fréquence de 0.1%. Dans une sous-étude de l'essai ANRS 106 Window chez 21 patients recevant un traitement intermittent comportant de l'efavirenz, des mutations K103N ont été mises en évidence chez 7 patients. La PCR allèle-spécifique a permis de détecter la présence de mutations K103N minoritaires non détectées par le génotypage standard. L'impact de ces mutations sur le contrôle de la virémie lors des phases de reprise du traitement semble cependant inconstant.TOULOUSE3-BU Santé-Centrale (315552105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

AES chez les internes (fréquence des accidents mais faible application des recommandations de prise en charge)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF