7 research outputs found
PremiÚre étude sur les profils sociodémographiques et nutritionnels de végétariens et végétaliens français, résultats de Nutrinet-Santé
PremiÚre étude sur les profils sociodémographiques et nutritionnels de végétariens et végétaliens français, résultats de Nutrinet-Santé. Journées francophones de la nutrition 201
Consumption of Ultra-Processed Foods by Pesco-Vegetarians, Vegetarians, and Vegans: Associations with Duration and Age at Diet Initiation
International audienc
viroCapt: A Bioinformatics Pipeline for Identifying Viral Insertion in Human Host Genome
International audienceIntroduction: The implication of viruses in human cancers, as well as the emergence of next generation sequencing has permitted to investigate further their role and pathophysiology in the development of this disease. One such mechanism is the integration of portions of viral genomes in the human genome, as well as the specific action of viral oncogenes.inding integration sites and preserved oncogenes is still relying on heavy manual intervention. Methods: We developed an analysis and interpretation pipeline to determine viral insertions. Using data from directed viral capture, the pipeline conducts a crude genotyping phase to select reference viral genomes, identifies chimeric reads, extracts the putative human sequences to locate in the human reference genome, scores and ranks candidate junctions, and exports tabular and visual results. Results: We leverage common bioinformatics tools (bowtie2, samtools, blat), and a dedicated filtering and ranking algorithm, implemented in R, to infer candidate junctions and insertions. Static results (tables, figures) are produced, as well as an interactive interpretation tool developed as a shiny web app. Discussion: We validated this pipeline against published results of HPV, HBV, and AAV2 insertions and show good information retrieval
Human iPSC-derived trigeminal neurons lack constitutive TLR3-dependent immunity that protects cortical neurons from HSV-1 infection
Herpes simplex virus type 1 (HSV-1) encephalitis (HSE) is the most common sporadic viral encephalitis in Western countries. Some HSE children carry inborn errors of the Toll-like receptor 3 (TLR3)-dependent IFN-\u3b1/\u3b2\u2013 and -\u3bb\u2013inducing pathway. Induced pluripotent stem cell (iPSC)-derived cortical neurons with TLR3 pathway mutations are highly susceptible to HSV-1, due to impairment of cell-intrinsic TLR3-IFN immunity. In contrast, the contribution of cell-intrinsic immunity of human trigeminal ganglion (TG) neurons remains unclear. Here, we describe efficient in vitro derivation and purification of TG neurons from human iPSCs via a cranial placode intermediate. The resulting TG neurons are of sensory identity and exhibit robust responses to heat (capsaicin), cold (icilin), and inflammatory pain (ATP). Unlike control cortical neurons, both control and TLR3-deficient TG neurons were highly susceptible to HSV-1. However, pretreatment of control TG neurons with poly(I:C) induced the cells into an anti\u2013HSV-1 state. Moreover, both control and TLR3-deficient TG neurons developed resistance to HSV-1 following pretreatment with IFN-\u3b2 but not IFN-\u3bb. These data indicate that TG neurons are vulnerable to HSV-1 because they require preemptive stimulation of the TLR3 or IFN-\u3b1/\u3b2 receptors to induce antiviral immunity, whereas cortical neurons possess a TLR3-dependent constitutive resistance that is sufficient to block incoming HSV-1 in the absence of prior antiviral signals. The lack of constitutive resistance in TG neurons in vitro is consistent with their exploitation as a latent virus reservoir in vivo. Our results incriminate deficiencies in the constitutive TLR3-dependent response of cortical neurons in the pathogenesis of HSE
Cyclin A2/E1 activation defines a hepatocellular carcinoma subclass with a rearrangement signature of replication stress
Cyclins A2 and E1 are known to regulate the cell cycle by promoting S phase entry and progression. Here, they identify an aggressive hepatocellular carcinoma subgroup exhibiting cyclin activation through various mechanisms and find this subgroup to display replication stress-induced structural rearrangements frequently activating TERT promoter
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A Drug Repurposing Approach Reveals Targetable Epigenetic Pathways in Plasmodium vivax Hypnozoites.
Radical cure of Plasmodium vivax malaria must include elimination of quiescent "hypnozoite" forms in the liver; however, the only FDA-approved treatments are contraindicated in many vulnerable populations. To identify new drugs and drug targets, we screened the Repurposing, Focused Rescue, and Accelerated Medchem library against P. vivax liver stages and identified the DNA methyltransferase inhibitors hydralazine and cadralazine as active against hypnozoites. We then used bisulfite sequencing and immunostaining to identify cytosine modifications in the infectious stage (sporozoites) and liver stages, respectively. A subsequent screen of epigenetic inhibitors revealed hypnozoites are broadly sensitive to histone acetyltransferase and methyltransferase inhibitors, indicating that several epigenetic mechanisms are likely modulating hypnozoite persistence. Our data present an avenue for the discovery and development of improved radical cure antimalarials