Ghrelin Stimulation of Growth Hormone-Releasing Hormone Neurons Is Direct in the Arcuate Nucleus

International audienceGhrelin targets the arcuate nucleus, from where growth hormone releasing hormone (GHRH) neurones trigger GH secretion. This hypothalamic nucleus also contains neuropeptide Y (NPY) neurons which play a master role in the effect of ghrelin on feeding. Interestingly, connections between NPY and GHRH neurons have been reported, leading to the hypothesis that the GH axis and the feeding circuits might be co-regulated by ghrelin.Here, we show that ghrelin stimulates the firing rate of identified GHRH neurons, in transgenic GHRH-GFP mice. This stimulation is prevented by growth hormone secretagogue receptor-1 antagonism as well as by U-73122, a phospholipase C inhibitor and by calcium channels blockers. The effect of ghrelin does not require synaptic transmission, as it is not antagonized by gamma-aminobutyric acid, glutamate and NPY receptor antagonists. In addition, this hypothalamic effect of ghrelin is independent of somatostatin, the inhibitor of the GH axis, since it is also found in somatostatin knockout mice. Indeed, ghrelin does not modify synaptic currents of GHRH neurons. However, ghrelin exerts a strong and direct depolarizing effect on GHRH neurons, which supports their increased firing rate. Thus, GHRH neurons are a specific target for ghrelin within the brain, and not activated secondary to altered activity in feeding circuits. These results support the view that ghrelin related therapeutic approaches could be directed separately towards GH deficiency or feeding disorders

Clinical spectrum of MTOR-related hypomelanosis of Ito with neurodevelopmental abnormalities.

PURPOSE: Hypomelanosis of Ito (HI) is a skin marker of somatic mosaicism. Mosaic MTOR pathogenic variants have been reported in HI with brain overgrowth. We sought to delineate further the pigmentary skin phenotype and clinical spectrum of neurodevelopmental manifestations of MTOR-related HI. METHODS: From two cohorts totaling 71 patients with pigmentary mosaicism, we identified 14 patients with Blaschko-linear and one with flag-like pigmentation abnormalities, psychomotor impairment or seizures, and a postzygotic MTOR variant in skin. Patient records, including brain magnetic resonance image (MRI) were reviewed. Immunostaining (n = 3) for melanocyte markers and ultrastructural studies (n = 2) were performed on skin biopsies. RESULTS: MTOR variants were present in skin, but absent from blood in half of cases. In a patient (p.[Glu2419Lys] variant), phosphorylation of p70S6K was constitutively increased. In hypopigmented skin of two patients, we found a decrease in stage 4 melanosomes in melanocytes and keratinocytes. Most patients (80%) had macrocephaly or (hemi)megalencephaly on MRI. CONCLUSION: MTOR-related HI is a recognizable neurocutaneous phenotype of patterned dyspigmentation, epilepsy, intellectual deficiency, and brain overgrowth, and a distinct subtype of hypomelanosis related to somatic mosaicism. Hypopigmentation may be due to a defect in melanogenesis, through mTORC1 activation, similar to hypochromic patches in tuberous sclerosis complex

Christ and the teacher of righteousness : The Evidence of the Dead Sea Scrolls

Baltimoreviii, 168 p.; 22 c

Conjectures sur les écrits de Qumran

La convergence de nombreux indices décelés par la critique interne amène à conclure que la Règle de la Communauté, la Règle de la Guerre et les Hymnes ont été composés par le même auteur, qui semble bien être le Docteur de Justice en personne ; en ce cas, la rédaction de ces ouvrages s'échelonnerait entre 130 et 100 avant Jésus-Christ. Au contraire, le Commentaire d'Habacuc et le Document de Damas trahissent une autre main un peu plus récente ; le temps des verbes montre que le Commentaire d'Habacuc a été composé avant la mort du Prêtre Impie (Alexandre Jannée ?), donc aux environs de 80 avant Jésus-Christ ; et l'évolution de la situation place le Document de Damas vers 60 ou 55 avant Jésus-Christ.Carmignac Jean. Conjectures sur les écrits de Qumran. In: Revue des Sciences Religieuses, tome 31, fascicule 2, 1957. pp. 140-168

Effect of habitat spatiotemporal structure on collembolan diversity

International audienceLandscape fragmentation is a major threat to biodiversity. It results in the transformation of continuous (hence large) habitat patches into isolated (hence smaller) patches, embedded in a matrix of another habitat type. Many populations are harmed by fragmentation because remnant patches do not fulfil their ecological and demographic requirements. In turn, this leads to a loss of biodiversity, especially if species have poor dispersal abilities. Moreover, landscape fragmentation is a dynamic process in which patches can be converted from one type of habitat to another. A recently created habitat might suffer from a reduced biodiversity because of the absence of adapted species that need a certain amount of time to colonize the new patch (e.g. direct meta-population effect). Thus landscape dynamics lead to complex habitat spatiotemporal structured, in which each patch is more or less continuous in space and time. In this study, we define habitat spatial structure as the degree to which a habitat is isolated from another habitat of the same kind and temporal structure as the time since the habitat is in place. Patches can also display reduced biodiversity because their spatial or temporal structures are correlated with habitat quality (e.g. indirect effects). We discriminated direct meta-community effects from indirect (habitat quality) effects of the spatiotemporal structure of habitats on biodiversity using Collembola as a model. We tested the relative importance of spatial and temporal structure of habitats for collembolan diversity, taking soil properties into account. In an agroforested landscape, we set up a sampling design comprised of two types of habitats (agriculture versus forest), a gradient of habitat isolation (three isolation classes) and two contrasting ages of habitats. Our results showed that habitat temporal structure is a key factor shaping collembolan diversity. A reduced diversity was detected in recent habitats, especially in forests. Interactions between temporal continuity and habitat quality were also detected by taking into account soil properties: diversity increased with soil carbon content, especially in old forests. Negative effects of habitat age on diversity were stronger in isolated patches. We conclude that habitat temporal structure is a key factor shaping collembolan diversity, while direction and amplitude of its effect depend on land use type and spatial isolation