Genome mapping of a LYST mutation in corn snakes indicates that vertebrate chromatophore vesicles are lysosome-related organelles.

Reptiles exhibit a spectacular diversity of skin colors and patterns brought about by the interactions among three chromatophore types: black melanophores with melanin-packed melanosomes, red and yellow xanthophores with pteridine- and/or carotenoid-containing vesicles, and iridophores filled with light-reflecting platelets generating structural colors. Whereas the melanosome, the only color-producing endosome in mammals and birds, has been documented as a lysosome-related organelle, the maturation paths of xanthosomes and iridosomes are unknown. Here, we first use 10x Genomics linked-reads and optical mapping to assemble and annotate a nearly chromosome-quality genome of the corn snake Pantherophis guttatus The assembly is 1.71 Gb long, with an N50 of 16.8 Mb and L50 of 24. Second, we perform mapping-by-sequencing analyses and identify a 3.9-Mb genomic interval where the lavender variant resides. The lavender color morph in corn snakes is characterized by gray, rather than red, blotches on a pink, instead of orange, background. Third, our sequencing analyses reveal a single nucleotide polymorphism introducing a premature stop codon in the lysosomal trafficking regulator gene (LYST) that shortens the corresponding protein by 603 amino acids and removes evolutionary-conserved domains. Fourth, we use light and transmission electron microscopy comparative analyses of wild type versus lavender corn snakes and show that the color-producing endosomes of all chromatophores are substantially affected in the LYST mutant. Our work provides evidence characterizing xanthosomes in xanthophores and iridosomes in iridophores as lysosome-related organelles

Iron oxidation at low temperature (260–500 C) in air and the effect of water vapor

The oxidation of iron has been studied at low temperatures (between 260 and 500 C) in dry air or air with 2 vol% H2O, in the framework of research on dry corrosion of nuclear waste containers during long-term interim storage. Pure iron is regarded as a model material for low-alloyed steel. Oxidation tests were performed in a thermobalance (up to 250 h) or in a laboratory furnace (up to 1000 h). The oxide scales formed were characterized using SEM-EDX, TEM, XRD, SIMS and EBSD techniques. The parabolic rate constants deduced from microbalance experiments were found to be in good agreement with the few existing values of the literature. The presence of water vapor in air was found to strongly influence the transitory stages of the kinetics. The entire structure of the oxide scale was composed of an internal duplex magnetite scale made of columnar grains and an external hematite scale made of equiaxed grains. 18O tracer experiments performed at 400 C allowed to propose a growth mechanism of the scale

Inhibition of Hedgehog Signaling Decreases Proliferation and Clonogenicity of Human Mesenchymal Stem Cells

Human mesenchymal stem cells (hMSC) have the ability to differentiate into osteoblasts, adipocytes and chondrocytes. We have previously shown that hMSC were endowed with a basal level of Hedgehog signaling that decreased after differentiation of these cells. Since hMSC differentiation is associated with growth-arrest we investigated the function of Hh signaling on cell proliferation. Here, we show that inhibition of Hh signaling, using the classical inhibitor cyclopamine, or a siRNA directed against Gli-2, leads to a decrease in hMSC proliferation. This phenomenon is not linked to apoptosis but to a block of the cells in the G0/G1 phases of the cell cycle. At the molecular level, it is associated with an increase in the active form of pRB, and a decrease in cyclin A expression and MAP kinase phosphorylation. Inhibition of Hh signaling is also associated with a decrease in the ability of the cells to form clones. By contrast, inhibition of Hh signaling during hMSC proliferation does not affect their ability to differentiate. This study demonstrates that hMSC are endowed with a basal Hedgehog signaling activity that is necessary for efficient proliferation and clonogenicity of hMSC. This observation unravels an unexpected new function for Hedgehog signaling in the regulation of human mesenchymal stem cells and highlights the critical function of this morphogen in hMSC biology

Characterization of globulin storage proteins of a low prolamin cereal species in relation to celiac disease

Brachypodium distachyon, a small annual grass with seed storage globulins as primary protein reserves was used in our study to analyse the toxic nature of non-prolamin seed storage proteins related to celiac disease. The main storage proteins of B. distachyon are the 7S globulin type proteins and the 11S, 12S seed storage globulins similar to oat and rice. Immunoblot analyses using serum samples from celiac disease patients were carried out followed by the identification of immune-responsive proteins using mass spectrometry. Serum samples from celiac patients on a gluten-free diet, from patients with Crohn's disease and healthy subjects, were used as controls. The identified proteins with intense serum-IgA reactivity belong to the 7S and 11-12S seed globulin family. Structure prediction and epitope predictions analyses confirmed the presence of celiac disease-related linear B cell epitope homologs and the presence of peptide regions with strong HLA-DQ8 and DQ2 binding capabilities. These results highlight that both MHC-II presentation and B cell response may be developed not only to prolamins but also to seed storage globulins. This is the first study of the non-prolamin type seed storage proteins of Brachypodium from the aspect of the celiac disease

Relationships between serum adiponectin and soluble TNF-α receptors and glucose and lipid oxidation in lean and obese subjects

Insulin resistance might be associated with an impaired ability of insulin to stimulate glucose oxidation and inhibit lipid oxidation. Insulin action is also inversely associated with TNF-α system and positively related to adiponectin. The aim of the present study was to analyze the associations between serum adiponectin, soluble TNF-α receptors concentrations and the whole-body insulin sensitivity, lipid and glucose oxidation, non-oxidative glucose metabolism (NOGM) and metabolic flexibility in lean and obese subjects. We examined 53 subjects: 25 lean (BMI < 25 kg × m−2) and 28 with overweight or obesity (BMI > 25 kg × m−2) with normal glucose tolerance. Hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Obese subjects had lower insulin sensitivity, adiponectin and higher sTNFR1 (all P < 0.001) and sTNFR2 (P = 0.001). Insulin sensitivity was positively related to adiponectin (r = 0.49, P < 0.001) and negatively related to sTNFR1 (r = −0.40, P = 0.004) and sTNFR2 (r = −0.52, P < 0.001). Adiponectin was related to the rate of glucose (r = 0.47, P < 0.001) and lipid (r = −0.40, P = 0.003) oxidation during the clamp, NOGM (r = 0.41, P = 0.002) and metabolic flexibility (r = 0.36, P = 0.007). Serum sTNFR1 and sTNFR2 were associated with the rate of glucose (r = −0.45, P = 0.001; r = −0.51, P < 0.001, respectively) and lipid (r = 0.52, P < 0.001; r = 0.46, P = 0.001, respectively) oxidation during hyperinsulinemia, NOGM (r = −0.31, P = 0.02; r = −0.43, P = 0.002, respectively) and metabolic flexibility (r = −0.47 and r = −0.51, respectively, both P < 0.001) in an opposite manner than adiponectin. Our data suggest that soluble TNF-α receptors and adiponectin have multiple effects on glucose and lipid metabolism in obesity

A Serum Factor Induces Insulin-Independent Translocation of GLUT4 to the Cell Surface which Is Maintained in Insulin Resistance

In response to insulin, glucose transporter GLUT4 translocates from intracellular compartments towards the plasma membrane where it enhances cellular glucose uptake. Here, we show that sera from various species contain a factor that dose-dependently induces GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes, human adipocytes, myoblasts and myotubes. Notably, the effect of this factor on GLUT4 is fully maintained in insulin-resistant cells. Our studies demonstrate that the serum-induced increase in cell surface GLUT4 levels is not due to inhibition of its internalization and is not mediated by insulin, PDGF, IGF-1, or HGF. Similarly to insulin, serum also augments cell surface levels of GLUT1 and TfR. Remarkably, the acute effect of serum on GLUT4 is largely additive to that of insulin, while it also sensitizes the cells to insulin. In accordance with these findings, serum does not appear to activate the same repertoire of downstream signaling molecules that are implicated in insulin-induced GLUT4 translocation. We conclude that in addition to insulin, at least one other biological proteinaceous factor exists that contributes to GLUT4 regulation and still functions in insulin resistance. The challenge now is to identify this factor

The genome of the emerging barley pathogen Ramularia collo-cygni

Background Ramularia collo-cygni is a newly important, foliar fungal pathogen of barley that causes the disease Ramularia leaf spot. The fungus exhibits a prolonged endophytic growth stage before switching life habit to become an aggressive, necrotrophic pathogen that causes significant losses to green leaf area and hence grain yield and quality. Results The R. collo-cygni genome was sequenced using a combination of Illumina and Roche 454 technologies. The draft assembly of 30.3 Mb contained 11,617 predicted gene models. Our phylogenomic analysis confirmed the classification of this ascomycete fungus within the family Mycosphaerellaceae, order Capnodiales of the class Dothideomycetes. A predicted secretome comprising 1053 proteins included redox-related enzymes and carbohydrate-modifying enzymes and proteases. The relative paucity of plant cell wall degrading enzyme genes may be associated with the stealth pathogenesis characteristic of plant pathogens from the Mycosphaerellaceae. A large number of genes associated with secondary metabolite production, including homologs of toxin biosynthesis genes found in other Dothideomycete plant pathogens, were identified. Conclusions The genome sequence of R. collo-cygni provides a framework for understanding the genetic basis of pathogenesis in this important emerging pathogen. The reduced complement of carbohydrate-degrading enzyme genes is likely to reflect a strategy to avoid detection by host defences during its prolonged asymptomatic growth. Of particular interest will be the analysis of R. collo-cygni gene expression during interactions with the host barley, to understand what triggers this fungus to switch from being a benign endophyte to an aggressive necrotroph