Natural Single-Nucleosome Epi-Polymorphisms in Yeast

Epigenomes commonly refer to the sequence of presence/absence of specific epigenetic marks along eukaryotic chromatin. Complete histone-borne epigenomes have now been described at single-nucleosome resolution from various organisms, tissues, developmental stages, or diseases, yet their intra-species natural variation has never been investigated. We describe here that the epigenomic sequence of histone H3 acetylation at Lysine 14 (H3K14ac) differs greatly between two unrelated strains of the yeast Saccharomyces cerevisiae. Using single-nucleosome chromatin immunoprecipitation and mapping, we interrogated 58,694 nucleosomes and found that 5,442 of them differed in their level of H3K14 acetylation, at a false discovery rate (FDR) of 0.0001. These Single Nucleosome Epi-Polymorphisms (SNEPs) were enriched at regulatory sites and conserved non-coding DNA sequences. Surprisingly, higher acetylation in one strain did not imply higher expression of the relevant gene. However, SNEPs were enriched in genes of high transcriptional variability and one SNEP was associated with the strength of gene activation upon stimulation. Our observations suggest a high level of inter-individual epigenomic variation in natural populations, with essential questions on the origin of this diversity and its relevance to gene x environment interactions

Recherche d un effet protecteur de HLA-G membranaire et soluble vis-à-vis de la toxicité des anticorps anti-HLA dirigés contre le donneur en transplantation rénale

L allo-immunisation post-greffe rénale représente un facteur important de la dysfonction chronique d allogreffe. Le développement de technologies sensibles pour la détection des anticorps soulève la question de la toxicité de ces anticorps. En effet, ceux-ci ne s accompagnent pas toujours d épisodes de rejet, traduisant alors un état d accommodation dont la physiopathologie reste incomprise. Connaissant les propriétés immuno-modulatrices de HLA-G, l objectif de notre étude est de rechercher un effet protecteur de cette molécule vis à vis de la toxicité sur le greffon des anticorps. Notre étude rétrospective a été menée sur les patients non immunisés en pré-greffe receveurs d une allogreffe rénale au CHU de Grenoble entre le 01/01/2005 et le 31/12/2009, divisés en 2 groupes : un groupe immunisé (n=28) regroupant les patients ayant développé des anticorps anti-HLA dirigés contre leur donneur ( donor specific antibodies , DSA) en post-greffe, divisés en 2 sous-groupes : DSA + rejet (n=16) se caractérisant par la survenue d un rejet et DSA + accommodation (n=12) comprenant les patients sans signes de toxicité des DSA ; un groupe non immunisé (n=22) comprenant les patients n ayant pas développé de DSA en post-greffe. Une comparaison de l expression de HLA-G membranaire et soluble a été effectuée à différents temps post-greffe. Notre étude confirme une association positive entre l expression de HLA-G membranaire et la survenue d un état d accommodation en présence de DSA (p=0.042) ainsi qu une tendance à une moindre incidence de (p=NS). Aucun effet protecteur de l isoforme soluble de la molécule n a été mis en évidence.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Determined about sex: Sex-testing in 45 primate species using a 2Y/1X sex-typing assay

International audienc

Comedications influence immune infiltration and pathological response to neoadjuvant chemotherapy in breast cancer

Immunosurveillance plays an important role in breast cancer (BC) prognosis and progression, and can be geared by immunogenic chemotherapy. In a cohort of 1023 BC patients treated with neoadjuvant chemotherapy (NAC), 40% of the individuals took comedications mostly linked to aging and comorbidities. We systematically analyzed the off-target effects of 1178 concurrent comedications (classified according to the Anatomical Therapeutic Chemical (ATC) Classification System) on the density of tumor-infiltrating lymphocytes (TILs) and pathological complete responses (pCR). At level 1 of the ATC system, the main anatomical classes of drugs were those targeting the nervous system (class N, 39.1%), cardiovascular disorders (class C, 26.6%), alimentary and metabolism (class A, 16.9%), or hormonal preparations (class H, 6.5%). At level 2, the most frequent therapeutic classes were psycholeptics (N05), analgesics (N02), and psychoanaleptics (N06). Pre-NAC TIL density in triple-negative BC (TNBC) was influenced by medications from class H, N, and A, while TIL density in HER2+ BC was associated with the use of class C. Psycholeptics (N05) and agents acting on the renin-angiotensin system (C09) were independently associated with pCR in the whole population of BC or TNBC, and in HER2-positive BC, respectively. Importantly, level 3 hypnotics (N05C) alone were able to reduce tumor growth in BC bearing mice and increased the anti-cancer activity of cyclophosphamide in a T cell-dependent manner. These findings prompt for further exploration of drugs interactions in cancer, and for prospective drug-repositioning strategies to improve the efficacy of NAC in BC

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed