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Introduction Legume crops are an important source of protein and oil for human health and in fixing atmospheric N2 for soil enrichment. With an objective to accelerate much-needed genetic analyses and breeding applications, draft genome assemblies were generated in several legume crops; many of them are not high quality because they are mainly based on short reads. However, the superior quality of genome assembly is crucial for a detailed understanding of genomic architecture, genome evolution, and crop improvement. Objectives Present study was undertaken with an objective of developing improved chromosome-length genome assemblies in six different legumes followed by their systematic investigation to unravel different aspects of genome organization and legume evolution. Methods We employed in situ Hi-C data to improve the existing draft genomes and performed different evolutionary and comparative analyses using improved genome assemblies. Results We have developed chromosome-length genome assemblies in chickpea, pigeonpea, soybean, subterranean clover, and two wild progenitor species of cultivated groundnut (A. duranensis and A. ipaensis). A comprehensive comparative analysis of these genome assemblies offered improved insights into various evolutionary events that shaped the present-day legume species. We highlighted the expansion of gene families contributing to unique traits such as nodulation in legumes, gravitropism in groundnut, and oil biosynthesis in oilseed legume crops such as groundnut and soybean. As examples, we have demonstrated the utility of improved genome assemblies for enhancing the resolution of “QTL-hotspot” identification for drought tolerance in chickpea and marker-trait associations for agronomic traits in pigeonpea through genome-wide association study. Genomic resources developed in this study are publicly available through an online repository, ‘Legumepedia’. Conclusion This study reports chromosome-length genome assemblies of six legume species and demonstrates the utility of these assemblies in crop improvement. The genomic resources developed here will have significant role in accelerating genetic improvement applications of legume crops.

SUMMARYT-Cell Factors (TCFs) are the main transcriptional effectors of Wnt/β-catenin signaling. TCF responsiveness is a hallmark of self-renewal in mouse embryonic, and adult, neural stem cells (NSC). However,in vivocontribution(s) of TCF activities in long-lived NSCs are poorly understood. Granule neuron progenitors (GNP) in the upper rhombic lip (URL) are long-lived NSCs which expressAtoh1and generate cerebellar granule neurons. Using functional and transcriptomic approaches in amphibian, we demonstrate that TCFs are active in the URL, and are strictly necessary for the emergence and maintenance of the GNP germinative zone. We identify BarH-like 1 (Barhl1), a direct target of Atoh1, as a gate keeper for GNP exit from the URL, through silencing of TCF transcriptional activity. Our transcriptomic andin silicoanalysis identifies Barhl1/TCF URL target genes, and confirms our functional data. Our study providesin vivoevidence that inhibition of TCF repressive activity is necessary for maintenance of the URL, a long-lived neural germinative niche.

Dynamic models using masses, dampers and springs have been developed to represent the behavior of energy piloted machines. These models were proven to estimate more accurately the required amount of energy to forge a part. But how to identify the parameters of the model to accurately represent the behavior of a specific machine? In this study, the case of a strike without billet on a screw press is investigated, different target functions are tested to identify the model parameters and a sensitivity study of the optimization is performed. Results are encouraging.

The Encyclopedia of DNA elements (ENCODE) project is a collaborative effort to create a comprehensive catalog of functional elements in the human genome. The current database comprises more than 19000 functional genomics experiments across more than 1000 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory and transcriptional landscape of theHomo sapiensandMus musculusgenomes. All experimental data, metadata, and associated computational analyses created by the ENCODE consortium are submitted to the Data Coordination Center (DCC) for validation, tracking, storage, and distribution to community resources and the scientific community. The ENCODE project has engineered and distributed uniform processing pipelines in order to promote data provenance and reproducibility as well as allow interoperability between genomic resources and other consortia. All data files, reference genome versions, software versions, and parameters used by the pipelines are captured and availableviathe ENCODE Portal. The pipeline code, developed using Docker and Workflow Description Language (WDL;https://openwdl.org/) is publicly available in GitHub, with images available on Dockerhub (https://hub.docker.com), enabling access to a diverse range of biomedical researchers. ENCODE pipelines maintained and used by the DCC can be installed to run on personal computers, local HPC clusters, or in cloud computing environmentsviaCromwell. Access to the pipelines and dataviathe cloud allows small labs the ability to use the data or software without access to institutional compute clusters. Standardization of the computational methodologies for analysis and quality control leads to comparable results from different ENCODE collections - a prerequisite for successful integrative analyses.Database URL:https://www.encodeproject.org/

Despite recent approvals, the response to treatment and prognosis of patients with advanced hepatocellular carcinoma (HCC) remain poor. Claudin-1 (CLDN1) is a membrane protein that is expressed at tight junctions, but it can also be exposed non-junctionally, such as on the basolateral membrane of the human hepatocyte. While CLDN1 within tight junctions is well characterized, the role of non-junctional CLDN1 and its role as a therapeutic target in HCC remains unexplored. Using humanized monoclonal antibodies (mAbs) specifically targeting the extracellular loop of human non-junctional CLDN1 and a large series of patient-derived cell-based and animal model systems we aimed to investigate the role of CLDN1 as a therapeutic target for HCC. Targeting non-junctional CLDN1 markedly suppressed tumor growth and invasion in cell line-based models of HCC and patient-derived 3D ex vivo models. Moreover, the robust effect on tumor growth was confirmed in vivo in a large series of cell line-derived xenograft and patient-derived xenograft mouse models. Mechanistic studies, including single-cell RNA sequencing of multicellular patient HCC tumorspheres, suggested that CLDN1 regulates tumor stemness, metabolism, oncogenic signaling and perturbs the tumor immune microenvironment. Our results provide the rationale for targeting CLDN1 in HCC and pave the way for the clinical development of CLDN1-specific mAbs for the treatment of advanced HCC. Hepatocellular carcinoma (HCC) is associated with high mortality and unsatisfactory treatment options. Herein, we identified the cell surface protein Claudin-1 as a treatment target for advanced HCC. Monoclonal antibodies targeting Claudin-1 inhibit tumor growth in patient-derived ex vivo and in vivo models by modulating signaling, cell stemness and the tumor immune microenvironment. Given the differentiated mechanism of action, the identification of Claudin-1 as a novel therapeutic target for HCC provides an opportunity to break the plateau of limited treatment response. The results of this preclinical study pave the way for the clinical development of Claudin-1-specific antibodies for the treatment of advanced HCC. It is therefore of key impact for physicians, scientists and drug developers in the field of liver cancer and gastrointestinal oncology. journal article research support, non-u.s. gov't 2023 Feb 2022 10 27 imported

Resume La presente etude porte sur le developpement d’un outil destine a mesurer les comportements inadaptes au travail. Cet outil a ete developpe aupres de directions d’ecole. Pour ce faire, des analyses factorielles exploratoires ont ete effectuees. Les donnees ont ete colligees aupres de 232 membres de la direction d’etablissements scolaires du Quebec. Les participants ont ete invites a repondre a un questionnaire en ligne. Les resultats obtenus permettent de categoriser les comportements inadaptes au travail en un facteur. En plus de sa valeur theorique, cette recherche comporte plusieurs contributions significatives pour la pratique.

Tissue fibrosis is a key driver of end-stage organ failure and cancer, overall accounting for up to 45% of deaths in developed countries. There is a large unmet medical need for antifibrotic therapies. Claudin-1 (CLDN1) is a member of the tight junction protein family. Although the role of CLDN1 incorporated in tight junctions is well established, the function of nonjunctional CLDN1 (njCLDN1) is largely unknown. Using highly specific monoclonal antibodies targeting a conformation-dependent epitope of exposed njCLDN1, we show in patient-derived liver three-dimensional fibrosis and human liver chimeric mouse models that CLDN1 is a mediator and target for liver fibrosis. Targeting CLDN1 reverted inflammation-induced hepatocyte profibrogenic signaling and cell fate and suppressed the myofibroblast differentiation of hepatic stellate cells. Safety studies of a fully humanized antibody in nonhuman primates did not reveal any serious adverse events even at high steady-state concentrations. Our results provide preclinical proof of concept for CLDN1-specific monoclonal antibodies for the treatment of advanced liver fibrosis and cancer prevention. Antifibrotic effects in lung and kidney fibrosis models further indicate a role of CLDN1 as a therapeutic target for tissue fibrosis across organs. In conclusion, our data pave the way for further therapeutic exploration of CLDN1-targeting therapies for fibrotic diseases in patients.

ORAL session EuMC35 Integration and Miniaturization of Filter Components; International audience; This paper presents the implementation of a new topology of 3D slow-wave transmission lines in CMOS technology. The proposed structure makes it possible to consider the design of compact circuits based on these 3D transmission lines presenting performances superior to the lumped elements approach (inductors and capacitors) for the Ka band, and in particular for 5G applications. The equivalent electrical model of the 3D structure, based on a physical analysis, is established, with excellent agreement with the measurement results. Then a filter based on parallel stubs is proposed in order to show the potentialities of the proposed 3D structure. The performances obtained are acceptable, with a power balance showing insertion loss potentially equal to 3 dB if the structure is matched, for a relative bandwidth of 22%. Development prospects concern the design of more complex filters but also of matching networks for LNAs or PAs.

Background Descriptions of cutaneous findings associated with COVID-19 have not been consistently accompanied by histopathology or confirmatory testing for SARS-CoV-2. Objective To describe and classify the cutaneous findings with supporting histopathology of confirmed COVID-19 inpatients. Methods We included consecutive inpatients with a confirmed diagnosis of COVID-19 for whom a dermatology consult was requested. A skin biopsy was performed in all cases. Skin findings were classified as being compatible with a cutaneous manifestation of COVID-19 or as representing a distinct clinical entity. Results Twenty-eight patients were studied in whom thirty-one dermatologic diagnoses were made. Twenty-two of the dermatoses were compatible with a cutaneous manifestation of COVID-19; nine entities were not associated with infection by SARS-CoV-2. The most common COVID-19-associated pattern was an exanthematous presentation. In four patients, a new pattern was observed, characterized by discrete papules with varied histopathological findings including a case of neutrophilic eccrine hidradenitis. No cases of pernio-like lesions were identified. Skin findings not associated with COVID-19 represented 29% of diagnoses and included Malassezia folliculitis, tinea, miliaria, and contact dermatitis. Limitations There is no gold-standard test to distinguish between viral exanthems and drug reactions. Conclusion A histopathological study is critical before attributing skin findings to a manifestation of COVID-19.

Chromatin architecture mapping in 3D formats has increased our understanding of how regulatory sequences and gene expression are connected and regulated in a genome. The 3D chromatin genome shows extensive remodeling during embryonic development, and although the cleavage-stage embryos of most species lack structure before zygotic genome activation (pre-ZGA), zebrafish has been reported to have structure. Here, we aimed to determine the chromosomal architecture in paternal/sperm zebrafish gamete cells to discern whether it either resembles or informs early pre-ZGA zebrafish embryo chromatin architecture. First, we assessed the higher-order architecture through advanced low-cell in situ Hi-C. The structure of zebrafish sperm, packaged by histones, lacks topological associated domains and instead displays “hinge-like” domains of ∼150 kb that repeat every 1–2 Mbs, suggesting a condensed repeating structure resembling mitotic chromosomes. The pre-ZGA embryos lacked chromosomal structure, in contrast to prior work, and only developed structure post-ZGA. During post-ZGA, we find chromatin architecture beginning to form at small contact domains of a median length of ∼90 kb. These small contact domains are established at enhancers, including super-enhancers, and chemical inhibition of Ep300a (p300) and Crebbpa (CBP) activity, lowering histone H3K27ac, but not transcription inhibition, diminishes these contacts. Together, this study reveals hinge-like domains in histone-packaged zebrafish sperm chromatin and determines that the initial formation of high-order chromatin architecture in zebrafish embryos occurs after ZGA primarily at enhancers bearing high H3K27ac.

Hepatocellular carcinoma (HCC) is a leading cause of death among cirrhotic patients, for which chemopreventive strategies are lacking. Recently, we developed a simple human cell-based system modeling a clinical prognostic liver signature (PLS) predicting liver disease progression and HCC risk. In a previous study, we applied our cell-based system for drug discovery and identified captopril, an approved angiotensin converting enzyme (ACE) inhibitor, as a candidate compound for HCC chemoprevention. Here, we explored ACE as a therapeutic target for HCC chemoprevention. Captopril reduced liver fibrosis and effectively prevented liver disease progression toward HCC development in a diethylnitrosamine (DEN) rat cirrhosis model and a diet-based rat model for nonalcoholic steatohepatitis–induced (NASH-induced) hepatocarcinogenesis. RNA-Seq analysis of cirrhotic rat liver tissues uncovered that captopril suppressed the expression of pathways mediating fibrogenesis, inflammation, and carcinogenesis, including epidermal growth factor receptor (EGFR) signaling. Mechanistic data in liver disease models uncovered a cross-activation of the EGFR pathway by angiotensin. Corroborating the clinical translatability of the approach, captopril significantly reversed the HCC high-risk status of the PLS in liver tissues of patients with advanced fibrosis. Captopril effectively prevents fibrotic liver disease progression toward HCC development in preclinical models and is a generic and safe candidate drug for HCC chemoprevention.

To evaluate the impact in maternity hospitals of using an embroidered "I sleep on my back" sleeping bag on observing the sleeping recommendations at 1 month after birth.This was a multicentere prospective study, exposed/unexposed type, in which mothers answered questionnaires (by telephone and online) 1 month after giving birth. The exposed group consisted of mothers who had given birth in a maternity hospital of the ELENA network in which the embroidered sleeping bag was used as a preventive action; the unexposed group of mothers gave birth in a maternity hospital of the RP2S network, without this specific preventive action.A total of 540 mothers participated in the study: 245 in the exposed group and 295 in the unexposed group. In the exposed group, 87.3% of infants slept exclusively on their back versus 75.9% in the unexposed group (P0.001); 91% of the mothers reported having actually used the sleeping bag. Except for room-sharing, compliance with the other sleeping recommendations was higher in the exposed group.Sleeping practices when infants were 1 month old were not optimal in our study population. A simple preventive initiative in maternity hospitals, using the embroidered "I sleep on my back" sleeping bags, is relevant and effective in improving compliance with the sleeping recommendations for infants at home.

Since its first discovery in the late 90s, Wnt canonical signaling has been demonstrated to affect a large variety of neural developmental processes, including, but not limited to, embryonic axis formation, neural proliferation, fate determination, and maintenance of neural stem cells. For decades, studies have focused on the mechanisms controlling the activity of β-catenin, the sole mediator of Wnt transcriptional response. More recently, the spotlight of research is directed towards the last cascade component, the T-cell factor (TCF)/Lymphoid-Enhancer binding Factor (LEF), and more specifically, the TCF/LEFmediated switch from transcriptional activation to repression, which in both embryonic blastomeres and mouse embryonic stem cells pushes the balance from pluri/multipotency towards differentiation. It has been long known that Groucho/Transducin-Like Enhancer of split (Gro/TLE) is the main co-repressor partner of TCF/LEF. More recently, other TCF/LEFinteracting partners have been identified, including the pro-neural BarH-Like 2 (BARHL2), which belongs to the evolutionary highly conserved family of homeodomain-containing transcription factors. This review describes the activities and regulatory modes of TCF/LEF as transcriptional repressors, with a specific focus on the functions of Barhl2 in vertebrate brain development. Specific attention is given to the transcriptional events leading to formation of the Organizer, as well as the roles and regulations of Wnt/β-catenin pathway in growth of the caudal forebrain. We present TCF/LEF activities in both embryonic and neural stem cells and discuss how alterations of this pathway could lead to tumors., Depuis sa première découverte à la fin des années 90, il a été démontré que la signalisation canonique Wnt affecte une grande variété de processus de développement neuronal, y compris, mais sans s'y limiter, la formation des axes embryonnaires, la prolifération neuronale, la détermination du destin et le maintien des cellules souches neurales. Pendant des décennies, les études se sont concentrées sur les mécanismes contrôlant l'activité de la β-caténine, l'unique médiateur de la réponse transcriptionnelle Wnt. Plus récemment, les recherches se sont concentrées sur le dernier composant de la cascade, le T-cell factor (TCF)/Lymphoid-Enhancer binding Factor (LEF), et plus précisément sur le passage de l'activation à la répression de la transcription médié par le TCF/LEF, qui, dans les blastomères embryonnaires et les cellules souches embryonnaires de souris, fait pencher la balance de la pluripotence vers la différenciation. On sait depuis longtemps que Groucho/Transducin-Like Enhancer of split (Gro/TLE) est le principal partenaire corépresseur de TCF/LEF. Plus récemment, d'autres partenaires d'interaction de TCF/LEF ont été identifiés, notamment le pro-neural BarH-Like 2 (BARHL2), qui appartient à la famille hautement conservée dans l'évolution des facteurs de transcription contenant des homéodomaines. Cette revue décrit les activités et les modes de régulation des TCF/LEF en tant que répresseurs transcriptionnels, avec un accent particulier sur les fonctions de Barhl2 dans le développement du cerveau des vertébrés. Une attention particulière est accordée aux événements transcriptionnels menant à la formation de l'Organisateur, ainsi qu'aux rôles et régulations de la voie Wnt/β-caténine dans la croissance du cerveau antérieur caudal. Nous présentons les activités de TCF/LEF dans les cellules souches embryonnaires et neurales et discutons de la manière dont les altérations de cette voie pourraient conduire à des tumeurs.

International audience; Felsic magmatic rocks (tonalites and trondhjemites) with calc-alkaline affinity were emplaced in SW Ecuador (Pascuales area; North Guayaquil) at ~87–89 Ma intruding the top of the basalts of the Caribean Large Igneous Province (CLIP), prior to the development of typical well-known island arcs from ~85 to 80 Ma onwards. A clear depletion of REE distinguishes the Pascuales felsic rocks from the more differentiated lavas of the Rio Cala Arc in Ecuador and from other Late Cretaceous arc-like felsic intrusives emplaced within the CLIP in Colombia and the Antilles. In addition, the Pascuales tonalites have very low K2O (

Aim Primary hyperparathyroidism (PHPT) is a common endocrine disorder, with an estimated incidence of 1/500 women and 1/2000 men older than 40 years. Several factors influence the positivity of preoperative scans including serum calcium, PTH and vitamin D levels, and gland size. The aim of our study is to examine the effect of biochemical adversity of primary hyperparathyroidism on preoperative imaging (SPECT-CT and US parathyroids). Method Retrospective study of 176 parathyroidectomies (2017-2020) in a tertiary referral centre with biochemistry, SPECT-CT, US parathyroids and histology outcomes being recorded. Failed parathyroidectomies were excluded. Results Patients were divided into 4 groups based on the preoperative calcium levels (normocalcemia 3.0 mmol/l, 14.2% of patients). Age (p-0.0297), preoperative vitamin D (p-0.03) and PTH levels (p-0.0001) were different while SPECT-CT positivity (p-0.29) weight of gland (p-0.015) and US positivity (p-0.09) were similar within the subgroups. Looking at the whole group, patients with positive SPECT-CT have a larger weight (p Conclusions Serum PTH levels and weight of the gland are directly correlated with positivity of preoperative imaging. Preoperative calcium and vitamin D levels correlates indirectly with the severity of the disease but did not influence the preoperative imaging positivity.

Chromatin looping plays an important role in genome regulation. However, because ChIP-seq and loop-resolution Hi-C (DNA-DNA proximity ligation) are extremely challenging in mammalian early embryos, the developmental stage at which cohesin-mediated loops form remains unknown. Here, we study early development in medaka (the Japanese killifish, Oryzias latipes) at 12 time points before, during, and after gastrulation (the onset of cell differentiation) and characterize transcription, protein binding, and genome architecture. We find that gastrulation is associated with drastic changes in genome architecture, including the formation of the first loops between sites bound by the insulator protein CTCF and a large increase in the size of contact domains. In contrast, the binding of the CTCF is fixed throughout embryogenesis. Loops form long after genome-wide transcriptional activation, and long after domain formation seen in mouse embryos. These results suggest that, although loops may play a role in differentiation, they are not required for zygotic transcription. When we repeated our experiments in zebrafish, loops did not emerge until gastrulation, that is, well after zygotic genome activation. We observe that loop positions are highly conserved in synteny blocks of medaka and zebrafish, indicating that the 3D genome architecture has been maintained for >110–200 million years of evolution.

Hepatitis B virus (HBV) envelopes as well as empty subviral particles carry in their lipid membranes the small (S), middle (M), and large (L) surface proteins, collectively known as hepatitis B surface antigen (HBsAg). Due to their common S domain all three proteins share a surface-exposed hydrophilic antigenic loop (AGL) with a complex disulfide bridge-dependent structure. The AGL is critical for HBV infectivity and virion secretion, and thus represents a major target for neutralizing antibodies. Previously, a human monoclonal antibody (mAb) targeting a conformational epitope in the AGL, IgG12, exhibited 1000-fold higher neutralizing activity than hepatitis B immune globulin (HBIG). Here we designed a single-chain variable fragment (scFv) homolog of IgG12, G12-scFv, which could be efficiently produced in soluble form in the cytoplasm of E. coli SHuffle cells. Independent in vitro assays verified specific binding of G12-scFv to a conformational S epitope shared with IgG12. Despite 20-fold lower affinity, G12-scFv but not an irrelevant scFv potently neutralized HBV infection of susceptible hepatoma cells (IC50 = 1.8 nM). Strikingly, low concentrations of G12-scFv blocked virion secretion from HBV producing cells (IC50 = 1.25 nM) without disturbing intracellular viral replication, whereas extracellular HBsAg was reduced only at >100-fold higher though still nontoxic concentration. The inhibitory effects correlated with S binding specificity and presumably also G12-scFv internalization into cells. Together these data suggest G12-scFv as a highly specific yet easily accessible novel tool for basic, diagnostic, and possibly future therapeutic applications.

BackgroundIn March 2020, many cases of COVID-19 were reported in three socially deprived neighbourhoods of the city of Perpignan, in the south of France, where large sedentary gypsy communities live. A study to measure seroprevalence was conducted in July 2020 to assess the level of contamination in these neighbourhoods after the first wave of the pandemic, and to identify factors associated with seropositivity.MethodsSCoPe is a cross-sectional survey conducted in selected persons aged six years old and over living in three neighbourhoods in Perpignan. Households were selected by systematic sampling and participants by random sampling. Collected blood samples were tested for SARS-CoV-2 IgG and IgM antibodies using the EIecsys® immunoassay to target the coronavirus’s spike protein. Antibody seroprevalence was estimated from weighted data and associated factors were investigated using multivariate logistic regression.ResultsThe seroprevalence of anti-SARS-CoV-2 antibodies was 35.4% (95% CI: 30.2-41.0). Over a fifth of seropositive individuals (21.7% ([14.1-31.8]) did not report any COVID-19 symptom. People aged 15-64 years old were at greater risk of seropositivity than those aged 65 years or over. Obesity prevalence was 40.7% (35.8-45.8) and obese people were more likely to be seropositive (aOR=2.0 [1.1-3.8]). The risk of being seropositive was higher in households with clinical COVID-19 cases (One case: aOR=2.5 [1.3-5.0]). In the neighbourhood with the highest measured seroprevalence, people living in a dwelling with 1-2 rooms had a higher risk of being seropositive than those living in a 4-room house (aOR=2.8 [1.2-6.3]). Working during the lockdown was associated with a lower risk of seropositivity (aOR=0.2 [0.03-1.0]).ConclusionTransmission prevalence of the SARS-COV-2 virus in this vulnerable population was very high during the COVID-19 pandemic’s first wave. Our results highlight the need to strengthen and adapt preventive measures by taking into account all social determinants of health, especially housing conditions.

Background & Purpose. Hepatocellular carcinoma (HCC) is the second leading and fastest rising cause of cancer death worldwide. HCC is often diagnosed when it is not curable. Thus, there are many challenges associated with the treatment of HCC. Until now there is no simple and robust system for reliable pre-treatment screening of approved drugs. Methods. We developed a simple and robust patient-derived multicellular cell clustering model from 18 liver resections. We applied this technology on 9 HCC liver tissues and assessed FDA-approved drug responses.Results. The success rate of our model is 100% independently from the type of liver underlying disease. The model shows differential responses to HCC targeted- and immune-based treatments with a high reproducibility. Our work highlights that preserving the integrity of the primary liver architecture permits to perpetuate the physiopathology. Conclusion. This model system will help to understand the biological role of the tumor microenvironment and to accelerate the clinical research program for personalized liver cancer treatment based on functional screening.

Introduction La pandémie de Covid-19 est apparue comme un révélateur des inégalités sociales de santé. En mars 2020, de nombreux cas ont été déclarés dans trois quartiers défavorisés où vit une importante communauté gitane. Une étude de séroprévalence a été menée en juillet 2020 afin d’évaluer le niveau de contamination dans ces quartiers à l’issue de la première vague et d’identifier des facteurs associés à la séropositivité. Matériels et méthodes Cette étude est une enquête transversale menée auprès de la population de 6 ans et plus de ces trois quartiers. Les logements ont été sélectionnés par tirage systématique et les participants par tirage aléatoire. Cette sélection a été réalisée par des enquêteurs terrain préalablement formés. La passation des questionnaires et les prélèvements sanguins des participants ont été effectués dans des centres Covid dédiés. Ces prélèvements ont été soumis à des tests de détection des anticorps IgG et IgM grâce au test immunologique EIecsys® Anti-SARS-CoV-2. La séroprévalence a été estimée sur les données redressées et des facteurs de risque associés ont été recherchés à partir d’un modèle de régression logistique. Résultats Au total, 700 personnes ont participé à l’étude. La séroprévalence des anticorps anti-SARS-CoV-2 était de 35,4% (IC95 % : 30,2–41,0), avec des variations significatives selon le quartier (13,9 %, 17,1 % et 46,7 %). Parmi les personnes séropositives, 21,7 % (14,1–31,8) n’avaient déclaré aucun symptôme entre le 24 février 2020 et la date d’enquête. Les femmes avaient un risque plus élevé d’être séropositives (odds ratio ajusté (ORa) = 1,8 [1,0–3,3], p = 0,034), de même que les personnes âgées de 15–64 ans en comparaison avec les personnes de 65 ans et plus (15–19 ans : ORa = 9,1 [2,8–29,8], p

Recombinant interferon-α (IFN-α) treatment functionally cures chronic hepatitis B virus (HBV) infection in some individuals and suppresses virus replication in hepatocytes infected in vitro. We studied the antiviral effect of conditioned media (CM) from peripheral blood mononuclear cells (PBMCs) stimulated with agonists of Toll-like receptors (TLRs) 2, 7, 8 and 9. We found that CM from PBMCs stimulated with dual-acting TLR7/8 (R848) and TLR2/7 (CL413) agonists were more potent drivers of inhibition of HBe and HBs antigen secretion from HBV-infected primary human hepatocytes (PHH) than CM from PBMCs stimulated with single-acting TLR7 (CL264) or TLR9 (CpG-B) agonists. Inhibition of HBV in PHH did not correlate with the quantity of PBMC-produced IFN-α, but it was a complex function of multiple secreted cytokines. More importantly, we found that the CM that efficiently inhibited HBV production in freshly isolated PHH via various cytokine repertoires and mechanisms did not reduce covalently closed circular (ccc)DNA levels. We confirmed our data with a cell culture model based on HepG2-NTCP cells and the plasmacytoid dendritic cell line GEN2.2. Collectively, our data show the importance of dual-acting TLR agonists inducing broad cytokine repertoires. The development of poly-specific TLR agonists provides novel opportunities towards functional HBV cure. journal article research support, non-u.s. gov't 2020 07 29 2020 07 29 imported

Early detection of infection with SARS-CoV-2 is key to managing the current global pandemic, as evidence shows the virus is most contagious on or before symptom onset. Here, we introduce a low-cost, high-throughput method for diagnosing and studying SARS-CoV-2 infection. Dubbed Pathogen-Oriented Low-Cost Assembly & Re-Sequencing (POLAR), this method amplifies the entirety of the SARS-CoV-2 genome. This contrasts with typical RT-PCR-based diagnostic tests, which amplify only a few loci. To achieve this goal, we combine a SARS-CoV-2 enrichment method developed by the ARTIC Network (https://artic.network/) with short-read DNA sequencing andde novogenome assembly. Using this method, we can reliably (>95% accuracy) detect SARS-CoV-2 at a concentration of 84 genome equivalents per milliliter (GE/mL). Almost all diagnostic methods currently authorized for use by the United States Food and Drug Administration with the Coronavirus Disease 2019 (COVID-19) Emergency Use Authorization require larger concentrations of the virus to achieve this degree of accuracy. In addition, we can reliably assemble the SARS-CoV-2 genome in the sample, often with no gaps and perfect accuracy. The genotypic data contained in these genome assemblies enable the more effective analysis of disease spread than is possible with an ordinary binary diagnostic. These data can also help identify vaccine and drug targets. Finally, we show that the diagnoses obtained using POLAR of both positive and negative clinical nasopharyngeal swab samples 100% match the diagnoses obtained in a clinical diagnostic lab using the Center for Disease Control’s 2019-Novel Coronavirus test. Using POLAR, a single person can manually process 192 samples over an 8- hour experiment at the cost of ∼$36 per patient (as of December 7th, 2022), enabling a 24-hour turnaround with sequencing and data analysis time. We anticipate that further testing and refinement will allow greater sensitivity in this approach.