Une approche d’intervention axée sur les femmes peut-elle appeler à la fois une analyse féministe et de développement des communautés ? Une réflexion à partir d’un récit de stage : le Red de Salud de Collique, au Pérou

À partir d’un récit de stage réalisé au Pérou, nous nous questionnons à savoir si les expériences d’intervention réalisées au Red de Salud de Collique, une approche d’intervention axée sur les femmes, appellent à la fois une analyse féministe et de développement des communautés (DC). Cette réflexion nous apparaît importante dans la perspective du défi de taille que pose l’arrimage des pratiques d’intervention sociale aux particularités de communautés dans lesquelles elles s’implantent.From an internship story produced in Peru, we are asking if the intervention experience Red de Salud from Collique (an intervention approach centrered around women) deals with both a feminist and community development (CD) analysis. This reflection appears to be important from a perspective where the main challenge is the link between social intervention practices and the characteristics of the communities in which they are being established

Serum Markers of Hepatocyte Death and Apoptosis Are Non Invasive Biomarkers of Severe Fibrosis in Patients with Alcoholic Liver Disease

BACKGROUND: Quantification of hepatocyte death is useful to evaluate the progression of alcoholic liver diseases. Our aims were to quantify and correlate the circulating levels of Cytokeratin 18 (CK18) and its caspases-generated fragment to disease severity in heavy alcoholics. METHODOLOGY/PRINCIPAL FINDINGS: CK18 and CK18-fragment were evaluated in the serum of 143 heavy alcoholics. Serum levels of markers of hepatocyte death (CK18), apoptosis (CK18 fragment) and necrosis (CK18 -CK18 fragment) increased in patients with severe fibrosis compared to patients with mild fibrosis. These markers strongly correlated with Mallory-Denk bodies, hepatocyte ballooning, fibrosis and with hepatic TNFα and TGFβ assessed in the liver of 24 patients. Elevated levels of serum hepatocyte death and apoptotic markers were independent risk factors in predicting severe fibrosis in a model combining alkaline phosphatase, bilirubin, prothrombin index, hyaluronate, hepatocyte death and apoptotic markers. The level of markers of hepatocyte death and apoptosis had an area under the receiving operator curve that predicted severe fibrosis of 0.84 and 0.76, respectively. CONCLUSION/SIGNIFICANCE: Death of hepatocytes can be easily evaluated with serum markers and correlated with severe fibrosis in heavy alcohol drinkers. These biomarkers could be useful to rapidly evaluate liver injuries and the efficacy of therapies

Unexpected Novel Relational Links Uncovered by Extensive Developmental Profiling of Nuclear Receptor Expression

Nuclear receptors (NRs) are transcription factors that are implicated in several biological processes such as embryonic development, homeostasis, and metabolic diseases. To study the role of NRs in development, it is critically important to know when and where individual genes are expressed. Although systematic expression studies using reverse transcriptase PCR and/or DNA microarrays have been performed in classical model systems such as Drosophila and mouse, no systematic atlas describing NR involvement during embryonic development on a global scale has been assembled. Adopting a systems biology approach, we conducted a systematic analysis of the dynamic spatiotemporal expression of all NR genes as well as their main transcriptional coregulators during zebrafish development (101 genes) using whole-mount in situ hybridization. This extensive dataset establishes overlapping expression patterns among NRs and coregulators, indicating hierarchical transcriptional networks. This complete developmental profiling provides an unprecedented examination of expression of NRs during embryogenesis, uncovering their potential function during central nervous system and retina formation. Moreover, our study reveals that tissue specificity of hormone action is conferred more by the receptors than by their coregulators. Finally, further evolutionary analyses of this global resource led us to propose that neofunctionalization of duplicated genes occurs at the levels of both protein sequence and RNA expression patterns. Altogether, this expression database of NRs provides novel routes for leading investigation into the biological function of each individual NR as well as for the study of their combinatorial regulatory circuitry within the superfamily

Aromatic maturity is a cornerstone of terroir expression in red wine

This article is published in cooperation with Terclim 2022 (XIVth International Terroir Congress and 2nd ClimWine Symposium), 3-8 July 2022, Bordeaux, France.Harvesting grapes at adequate maturity is key to the production of high-quality red wines. Viticulturists, enologists, and wine makers define several types of maturity, including physiological maturity, technological maturity, phenolic maturity, and aromatic maturity. Physiological maturity is a biological concept. Technological maturity and phenolic maturity are relatively well documented in the scientific literature, being linked to quantifiable compounds in grape must. Articles on aromatic maturity are scarcer. This is surprising, because aromatic maturity is, probably, the most important of the four in determining wine quality and typicity, including terroir expression, i.e.  the identifiable taste of wine in relation to its origin. Optimal terroir expression can be obtained when technological, phenolic, and aromatic maturity are reached at the same time, or within a short time frame. This is more likely to occur when the ripening takes place under mild temperatures, neither too cool, nor too hot.Aromatic expression in wine can be driven, in order from low to high maturity, by green, herbal, spicy, floral, fresh fruit, ripe fruit, jammy fruit, dried fruit, candied, or cooked fruit aromas. Green and cooked fruit aromas are not desirable in red wines, while the levels of other aromatic nuances contribute to the typicity of the wine in relation to its place of origin. Wines produced in cool climates, or on cool soils in temperate climates, are likely to express herbal or fresh fruit aromas, while wines produced under warm climates, or on warm soils in temperate climates, may express ripe fruit, jammy fruit, or candied fruit aromas.This article reviews the state of the art of compounds underpinning the aromas of wines obtained from grapes harvested at different stages of maturity. Advances in the understanding of how aromatic maturity shapes terroir expression and how it can be manipulated by variety choices and management practices, under current and future climatic conditions, are shown. Early ripening varieties perform better in cool climates and late ripening varieties in warm climates. Additionally, maturity can be advanced or delayed by different canopy management practices or training systems. Timing of harvest also impacts aromatic expression of the produced wine. Gaps in the literature are highlighted to guide future directions of research

HIF2α reduces growth rate but promotes angiogenesis in a mouse model of neuroblastoma

<p>Abstract</p> <p>Background</p> <p>HIF2α/EPAS1 is a hypoxia-inducible transcription factor involved in catecholamine homeostasis, vascular remodelling, physiological angiogenesis and adipogenesis. It is overexpressed in many cancerous tissues, but its exact role in tumour progression remains to be clarified.</p> <p>Methods</p> <p>In order to better establish its function in tumourigenesis and tumour angiogenesis, we have stably transfected mouse neuroblastoma N1E-115 cells with the native form of HIF2α or with its dominant negative mutant, HIF2α (1–485) and studied their phenotype <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p><it>In vitro </it>studies reveal that HIF2α induces neuroblastoma cells hypertrophy and decreases their proliferation rate, while its inactivation by the HIF2α (1–485) mutant leads to a reduced cell size, associated with an accelerated proliferation. However, our <it>in vivo </it>experiments show that subcutaneous injection of cells overexpressing HIF2α into syngenic mice, leads to the formation of tumour nodules that grow slower than controls, but that are well structured and highly vascularized. In contrast, HIF2α (1–485)-expressing neuroblastomas grow fast, but are poorly vascularized and quickly tend to extended necrosis.</p> <p>Conclusion</p> <p>Together, our data reveal an unexpected combination between an antiproliferative and a pro-angiogenic function of HIF2α that actually seems to be favourable to the establishment of neuroblastomas <it>in vivo</it>.</p

Muscle inactivation of mTOR causes metabolic and dystrophin defects leading to severe myopathy

Mammalian target of rapamycin (mTOR) is a key regulator of cell growth that associates with raptor and rictor to form the mTOR complex 1 (mTORC1) and mTORC2, respectively. Raptor is required for oxidative muscle integrity, whereas rictor is dispensable. In this study, we show that muscle-specific inactivation of mTOR leads to severe myopathy, resulting in premature death. mTOR-deficient muscles display metabolic changes similar to those observed in muscles lacking raptor, including impaired oxidative metabolism, altered mitochondrial regulation, and glycogen accumulation associated with protein kinase B/Akt hyperactivation. In addition, mTOR-deficient muscles exhibit increased basal glucose uptake, whereas whole body glucose homeostasis is essentially maintained. Importantly, loss of mTOR exacerbates the myopathic features in both slow oxidative and fast glycolytic muscles. Moreover, mTOR but not raptor and rictor deficiency leads to reduced muscle dystrophin content. We provide evidence that mTOR controls dystrophin transcription in a cell-autonomous, rapamycin-resistant, and kinase-independent manner. Collectively, our results demonstrate that mTOR acts mainly via mTORC1, whereas regulation of dystrophin is raptor and rictor independent

The Osteopontin Level in Liver, Adipose Tissue and Serum Is Correlated with Fibrosis in Patients with Alcoholic Liver Disease

<div><h3>Background</h3><p>Osteopontin (OPN) plays an important role in the progression of chronic liver diseases. We aimed to quantify the liver, adipose tissue and serum levels of OPN in heavy alcohol drinkers and to compare them with the histological severity of hepatic inflammation and fibrosis.</p> <h3>Methodology/Principal Findings</h3><p>OPN was evaluated in the serum of a retrospective and prospective group of 109 and 95 heavy alcohol drinkers, respectively, in the liver of 34 patients from the retrospective group, and in the liver and adipose tissue from an additional group of 38 heavy alcohol drinkers. Serum levels of OPN increased slightly with hepatic inflammation and progressively with the severity of hepatic fibrosis. Hepatic OPN expression correlated with hepatic inflammation, fibrosis, TGFβ expression, neutrophils accumulation and with the serum OPN level. Interestingly, adipose tissue OPN expression also correlated with hepatic fibrosis even after 7 days of alcohol abstinence. The elevated serum OPN level was an independent risk factor in estimating significant (F≥2) fibrosis in a model combining alkaline phosphatase, albumin, hemoglobin, OPN and FibroMeter® levels. OPN had an area under the receiving operator curve that estimated significant fibrosis of 0.89 and 0.88 in the retrospective and prospective groups, respectively. OPN, Hyaluronate (AUROC: 0.88), total Cytokeratin 18 (AUROC: 0.83) and FibroMeter® (AUROC: 0.90) estimated significance to the same extent in the retrospective group. Finally, the serum OPN levels also correlated with hepatic fibrosis and estimated significant (F≥2) fibrosis in 86 patients with chronic hepatitis C, which suggested that its elevated level could be a general response to chronic liver injury.</p> <h3>Conclusion/Significance</h3><p>OPN increased in the liver, adipose tissue and serum with liver fibrosis in alcoholic patients. Further, OPN is a new relevant biomarker for significant liver fibrosis. OPN could thus be an important actor in the pathogenesis of this chronic liver disease.</p> </div

Emotional and attention-deficit/hyperactivity disorder symptoms of preterm vs. full-term children during COVID-19 pandemic restrictions

BACKGROUND: Preterm children are at higher risk of developing mental health problems than full-term children. Deterioration of children's mental health was observed during COVID-19 pandemic restrictive measures. Our study compared emotional and attention-deficit/hyperactivity disorder (ADHD) symptoms during school closure between preterm and full-term children. METHODS: Data from two French birth cohorts-ELFE and EPIPAGE-2-were used. In 2011, infants born ≥22 weeks' gestation were recruited. Parents completed the Strengths and Difficulties Questionnaire when the children were 9 years old and experiencing school closure. Multivariate multinomial logistic regression models were used. RESULTS: Subjects included 4164 full-term and 1119 preterm children. In univariate analyses, compared to full-term children: extremely and very preterm children more frequently had abnormal and borderline ADHD scores (odds ratio [OR] 1.86, 95% confidence interval [CI] 1.50-2.30, OR 1.42, 95% CI 1.08-1.85, respectively) and abnormal emotional scores (OR 1.86, 95% CI 1.43-2.40); moderate to late preterm children more often had abnormal ADHD scores (OR 1.33, 95% CI 1.01-1.78). The associations did not remain when previous symptoms at 5 years old were considered. CONCLUSIONS: School closure during lockdown did not appear to increase the risk of mental health problems in preterm compared to full-term children. IMPACT STATEMENT: Preterm children are at higher risk of developing mental health problems than full-term children. Deterioration in children's mental health was observed during COVID-19 pandemic restrictions. However, whether preterm children were a particularly vulnerable subgroup during school closure is unclear. In univariate analyses, extremely and very preterm children more often had abnormal and borderline ADHD symptoms and abnormal emotional symptom scores than full-term children. The associations did not remain significantly associated when previous symptoms were considered. Preterm compared to full-term children more often suffer from ADHD and emotional symptoms, but school closure during lockdown did not appear to increase this risk.Santé, perception, pratiques, relations et inégalités sociales en population générale pendant la crise COVID-1