French Institute of Health and Medical Research

About: French Institute of Health and Medical Research is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Receptor. The organization has 109367 authors who have published 174236 publications receiving 8365503 citations.

Human Splicing Finder: an online bioinformatics tool to predict splicing signals

Abstract: Thousands of mutations are identified yearly. Although many directly affect protein expression, an increasing proportion of mutations is now believed to influence mRNA splicing. They mostly affect existing splice sites, but synonymous, non-synonymous or nonsense mutations can also create or disrupt splice sites or auxiliary cis-splicing sequences. To facilitate the analysis of the different mutations, we designed Human Splicing Finder (HSF), a tool to predict the effects of mutations on splicing signals or to identify splicing motifs in any human sequence. It contains all available matrices for auxiliary sequence prediction as well as new ones for binding sites of the 9G8 and Tra2-beta Serine-Arginine proteins and the hnRNP A1 ribonucleoprotein. We also developed new Position Weight Matrices to assess the strength of 5' and 3' splice sites and branch points. We evaluated HSF efficiency using a set of 83 intronic and 35 exonic mutations known to result in splicing defects. We showed that the mutation effect was correctly predicted in almost all cases. HSF could thus represent a valuable resource for research, diagnostic and therapeutic (e.g. therapeutic exon skipping) purposes as well as for global studies, such as the GEN2PHEN European Project or the Human Variome Project.

A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction

Abstract: The adipocyte-specific hormone leptin, the product of the obese (ob) gene, regulates adipose-tissue mass through hypothalamic effects on satiety and energy expenditure Leptin acts through the leptin receptor, a single-transmembrane-domain receptor of the cytokine-receptor family In rodents, homozygous mutations in genes encoding leptin or the leptin receptor cause early-onset morbid obesity, hyperphagia and reduced energy expenditure These rodents also show hypercortisolaemia, alterations in glucose homeostasis, dyslipidaemia, and infertility due to hypogonadotropic hypogonadisms In humans, leptin deficiency due to a mutation in the leptin gene is associated with early-onset obesity Here we describe a homozygous mutation in the human leptin receptor gene that results in a truncated leptin receptor lacking both the transmembrane and the intracellular domains In addition to their early-onset morbid obesity, patients homozygous for this mutation have no pubertal development and their secretion of growth hormone and thyrotropin is reduced These results indicate that leptin is an important physiological regulator of several endocrine functions in humans

Three parietal circuits for number processing

Abstract: Did evolution endow the human brain with a predisposition to represent and acquire knowledge about numbers? Although the parietal lobe has been suggested as a potential substrate for a domain-specific representation of quantities, it is also engaged in verbal, spatial, and attentional functions that may contribute to calculation. To clarify the organisation of number-related processes in the parietal lobe, we examine the three-dimensional intersection of fMRI activations during various numerical tasks, and also review the corresponding neuropsychological evidence. On this basis, we propose a tentative tripartite organisation. The horizontal segment of the intraparietal sulcus (HIPS) appears as a plausible candidate for domain specificity: It is systematically activated whenever numbers are manipulated, independently of number notation, and with increasing activation as the task puts greater emphasis on quantity processing. Depending on task demands, we speculate that this core quantity system, analogous t...

Innate or Adaptive Immunity? The Example of Natural Killer Cells

Abstract: Natural killer (NK) cells were originally defined as effector lymphocytes of innate immunity endowed with constitutive cytolytic functions. More recently, a more nuanced view of NK cells has emerged. NK cells are now recognized to express a repertoire of activating and inhibitory receptors that is calibrated to ensure self-tolerance while allowing efficacy against assaults such as viral infection and tumor development. Moreover, NK cells do not react in an invariant manner but rather adapt to their environment. Finally, recent studies have unveiled that NK cells can also mount a form of antigen-specific immunologic memory. NK cells thus exert sophisticated biological functions that are attributes of both innate and adaptive immunity, blurring the functional borders between these two arms of the immune response.