Terrestrial isopods from the Oued Laou basin,north-eastern Morocco (Crustacea: Oniscidea), with descriptions of two new genera and seven new species

Thirty-four species of terrestrial isopods (Crustacea: Oniscidea) from the Oued Laou basin, in the Rif area of north-eastern Morocco, are recorded. One genus (Paractenoscia) and seven species (Trichoniscus microphthalmus, Paractenoscia cavernicola, Bathytropa rifensis, Soteriscus gibbosus, S. laouensis, Porcellio pseudornatus, and Eluma praticola) are described as new. The genus Soteriscus, unavailable according to article 13.3 of the International Commission on Zoological Nomenclature (ICZN), is here revalidated by choosing S. gaditanus as type species. Six species (Graeconiscus thermophilus, Ctenoscia minima, Platyarthrus parisii, Porcellio humberti, Porcellio flavocinctus and Eluma caelata) have been fully illustrated to facilitate their identifications. Ctenoscia dorsalis Verhoeff is considered to be a junior synonym of C. minima Dollfus. Porcellio ornatus from southern Spain is also figured for comparison with P. pseudornatus sp. nov. The composition and origin of the oniscidean fauna of the Rif region is briefly discussed.

http://zoobank.org/urn:lsid:zoobank.org:pub:DCBF3103-1463-4A32-9BC0-A4CFE8B762AE     

Postzygotic HRAS and KRAS mutations cause nevus sebaceous and Schimmelpenning syndrome

Nevus sebaceous is a common congenital cutaneous malformation. Affected individuals may develop benign and malignant secondary tumors in the nevi during life. Schimmelpenning syndrome is characterized by the association of nevus sebaceous with extracutaneous abnormalities. We report that of 65 sebaceous nevi studied, 62 (95%) had mutations in the HRAS gene and 3 (5%) had mutations in the KRAS gene. The HRAS c.37G>C mutation, which results in a p.Gly13Arg substitution, was present in 91% of lesions. Nonlesional tissues from 18 individuals had a wild-type sequence, confirming genetic mosaicism. The HRAS c.37G>C mutation was also found in 8 of 8 associated secondary tumors. Mosaicism for HRAS c.37G>C and KRAS c.35G>A mutations was found in two individuals with Schimmelpenning syndrome. Functional analysis of HRAS c.37G>C mutant cells showed constitutive activation of the MAPK and PI3K-Akt signaling pathways. Our results indicate that nevus sebaceous and Schimmelpenning syndrome are caused by postzygotic HRAS and KRAS mutations. These mutations may predispose individuals to the development of secondary tumors in nevus sebaceous.     

Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes

Genome-wide association studies have revealed that common noncoding variants in MTNR1B (encoding melatonin receptor 1B, also known as MT(2)) increase type 2 diabetes (T2D) risk(1,2). Although the strongest association signal was highly significant (P < 1 × 10(-20)), its contribution to T2D risk was modest (odds ratio (OR) of ～1.10-1.15)(1-3). We performed large-scale exon resequencing in 7,632 Europeans, including 2,186 individuals with T2D, and identified 40 nonsynonymous variants, including 36 very rare variants (minor allele frequency (MAF) <0.1%), associated with T2D (OR = 3.31, 95% confidence interval (CI) = 1.78-6.18; P = 1.64 × 10(-4)). A four-tiered functional investigation of all 40 mutants revealed that 14 were non-functional and rare (MAF < 1%), and 4 were very rare with complete loss of melatonin binding and signaling capabilities. Among the very rare variants, the partial- or total-loss-of-function variants but not the neutral ones contributed to T2D (OR = 5.67, CI = 2.17-14.82; P = 4.09 × 10(-4)). Genotyping the four complete loss-of-function variants in 11,854 additional individuals revealed their association with T2D risk (8,153 individuals with T2D and 10,100 controls; OR = 3.88, CI = 1.49-10.07; P = 5.37 × 10(-3)). This study establishes a firm functional link between MTNR1B and T2D risk.     

Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein

Rapid and efficient removal of apoptotic cells by phagocytes is important during development, tissue homeostasis and in immune responses. Efficient clearance depends on the capacity of a single phagocyte to ingest multiple apoptotic cells successively, and to process the corpse-derived cellular material. However, the factors that influence continued clearance by phagocytes are not known. Here we show that the mitochondrial membrane potential of the phagocyte critically controls engulfment capacity, with lower potential enhancing engulfment and vice versa. The mitochondrial membrane protein Ucp2, which acts to lower the mitochondrial membrane potential, was upregulated in phagocytes engulfing apoptotic cells. Loss of Ucp2 reduced phagocytic capacity, whereas Ucp2 overexpression enhanced engulfment. Mutational and pharmacological studies indicated a direct role for Ucp2-mediated mitochondrial function in phagocytosis. Macrophages from Ucp2-deficient mice were impaired in phagocytosis in vitro, and Ucp2-deficient mice showed profound in vivo defects in clearing dying cells in the thymus and testes. Collectively, these data indicate that mitochondrial membrane potential and Ucp2 are key molecular determinants of apoptotic cell clearance. As Ucp2 is linked to metabolic diseases and atherosclerosis, this newly discovered role for Ucp2 in apoptotic cell clearance has implications for the complex aetiology and pathogenesis of these diseases.     

Central powering of the largest Lyman-α nebula is revealed by polarized radiation

High-redshift Lyman-α (Lyα) blobs are extended, luminous but rare structures that seem to be associated with the highest peaks in the matter density of the Universe. Their energy output and morphology are similar to those of powerful radio galaxies, but the source of the luminosity is unclear. Some blobs are associated with ultraviolet or infrared bright galaxies, suggesting an extreme starburst event or accretion onto a central black hole. Another possibility is gas that is shock-excited by supernovae. But not all blobs are associated with galaxies, and these ones may instead be heated by gas falling into a dark-matter halo. The polarization of the Lyα emission can in principle distinguish between these options, but a previous attempt to detect this signature returned a null detection. Here we report observations of polarized Lyα from the blob LAB1 (ref. 2). Although the central region shows no measurable polarization, the polarized fraction (P) increases to ～20 per cent at a radius of 45?kiloparsecs, forming an almost complete polarized ring. The detection of polarized radiation is inconsistent with the in situ production of Lyα photons, and we conclude that they must have been produced in the galaxies hosted within the nebula, and re-scattered by neutral hydrogen.     

New gene functions in megakaryopoiesis and platelet formation

Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.