82 research outputs found

    Cell cycle regulation in hematopoietic stem cells

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    Hematopoietic stem cells (HSCs) give rise to all lineages of blood cells. Because HSCs must persist for a lifetime, the balance between their proliferation and quiescence is carefully regulated to ensure blood homeostasis while limiting cellular damage. Cell cycle regulation therefore plays a critical role in controlling HSC function during both fetal life and in the adult. The cell cycle activity of HSCs is carefully modulated by a complex interplay between cell-intrinsic mechanisms and cell-extrinsic factors produced by the microenvironment. This fine-tuned regulatory network may become altered with age, leading to aberrant HSC cell cycle regulation, degraded HSC function, and hematological malignancy

    Association of Forced Vital Capacity with the Developmental Gene <i>NCOR2</i>

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    Background Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes. Methods Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 chi

    Forty years of carabid beetle research in Europe - from taxonomy, biology, ecology and population studies to bioindication, habitat assessment and conservation

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    Volume: 100Start Page: 55End Page: 14

    Rôle de l'alimentation dans le développement de la glande mammaire et la lactation chez le lapin

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    The nutritional status of the women, in particular during critical periods such as childhood and adolescence, can have long-term effects on lactation. Although similar phenomena are described in animal models, mechanisms responsible for these alterations are only partially known. In the present work, we first studied leptin gene expression in the rabbit mammary gland. Rabbit leptin cDNA cloning allowed us on the one hand to deduce the primary structure of the protein and, on the other hand to compare rabbit leptin to that of other species. We showed that leptin mRNA and protein were present in the mammary gland of rabbit during pregnancy and lactation. The quantitative analysis by real time RT-PCR showed that the level of expression of leptin mRNA in the mammary gland increased from the end of the pregnancy to reach at mid-lactation a level equivalent to that of the adipose tissue, while that of leptin receptors was higher during pregnancy as compared to lactation. The cellular localization of leptin mRNA and protein revealed a specific expression in mammary luminal epithelial cells. These results suggest that leptin plays an autocrine and/or paracrine role in the mammary gland and can thus constitute a major mediator acting in the local regulation of the mammary development. By using a model of diet-induced obese rabbits, we were able to study the consequences of the nutritional changes during the neonatal and from the prepubertal periods on adult mammary phenotype. Newborn rabbits were suckled by dams fed a high-fat/high-sugar obesogenic (OB) or a control (T) diet starting before puberty and extending until the end of lactation. They were subsequently fed either the OB, or T diets, as before the onset of puberty and throughout early pregnancy. Mammary glands were collected on Day 8 of pregnancy. Rabbits fed with OD milk and subjected to an OD diet displayed an abnormal development of the mammary gland. Furthermore, we analysed the expression of leptin in the mammary gland. Mammary leptin mRNA was strongly expressed in rabbits fed with OD milk and subjected to an OD diet, by comparison with controls. Taken together, these data suggest that early-life nutritional history can determine subsequent mammary gland development. Moreover since leptin has been shown to be involved in several developmental processes, our results highlight the potentially important regulatory role that this cytokine may play during critical early-life nutritional windows with respect to long-term growth and mammary function.Le statut nutritionnel des femmes, en particulier au cours de l’enfance et de l’adolescence, peut influencer ultérieurement l’allaitement et de ce fait, perturber la fonction de lactation en altérant le développement mammaire. Bien que chez des animaux, des phénomènes similaires aient été décrits, les mécanismes responsables de ces perturbations au niveau mammaire ne sont que partiellement connus. Le travail de cette thèse est réparti en deux volets. Dans un premier temps, nous avons étudié le gène de la leptine chez le lapin. Le clonage de l’ADNc codant pour la leptine de lapin ainsi que la détermination de sa structure nucléotidique ont permis d’une part de déduire la structure primaire de la protéine et, d’autre part de pouvoir la comparer à celle d’autres espèces. Nous avons montré que les ARNm codant pour la leptine et la protéine étaient présents au niveau de la glande mammaire de lapin pendant la gestation et la lactation. L’analyse quantitative par RT-PCR en temps réel a montré que le niveau d’expression des ARNm codant pour la leptine augmentait à partir de la fin de la gestation pour atteindre un niveau équivalent à celui du tissu adipeux à mi-lactation. L’analyse de la localisation cellulaire de la leptine révèle une expression spécifique dans les cellules épithéliales luminales. Ces résultats suggèrent que la leptine via un rôle autocrine et/ou paracrine pourrait constituer un médiateur important dans la régulation locale du développement mammaire. Dans un second temps, un modèle de lapine à adiposité élevée ayant été développé au laboratoire, nous nous sommes intéressés aux conséquences de celle-ci sur la lactation et sur le phénotype mammaire de la descendance. Deux cohortes de lapines ont reçu ou non le régime obésogène (régime hyperglucidique et hyperlipidique dit OB) avant la puberté jusque leur mise-bas. Les lapereaux femelles (F1) ont été répartis de manière aléatoire sous les deux groupes de lapines. Au sevrage, les femelles F1 ont-elles-mêmes été soumises soit à un régime témoin, soit au régime obésogène. Ces travaux nous ont permis de montrer que le lait provenant d’animaux ayant ingéré le régime obésogène, combiné à un régime obésogène, pouvait provoquer des altérations importantes au niveau du phénotype mammaire chez la descendance. L’ensemble de ce travail soutient l’hypothèse selon laquelle le lait maternel, dont la composition peut être altérée selon l’alimentation de la mère, influerait sur le développement mammaire de la descendance
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