10 research outputs found

    Grain Surface Models and Data for Astrochemistry

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    AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of ∌25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions

    Males with high levels of oxidative damage form weak pair bonds in a gregarious bird species

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    International audienceThe number and quality of social bonds can have major consequences for fitness. For example, in socially monogamous species with biparental care, pair bond quality has been linked to the latency to breed as well as the number and survival of offspring. Given these benefits, what mechanisms prevent someindividuals from forming strong pair bonds? Markers of physiological stress and ageing, such as oxidative stress and telomere length, might mediate individual differences in behavioural performance. However, the possibility that physiological stress could also constrain the strength of the pair bond has rarely been investigated. We show that in captive colonies of the socially monogamous, gregarious zebra finch, Taeniopygia guttata, individuals with higher levels of plasma lipid oxidative damage formed weaker pair bonds. This effect was sex specific: while males with more oxidative damage spent less time in bodily contact with their prospective breeding partners, no such link was found in females. Although females experienced higher absolute levels of plasma oxidative damage, pair bond investment may have been more constrained in males due to the costly expression of their sexually selected traits. Pair bondstrength was not associated with levels of the key antioxidant glutathione or with telomere length. Individuals’ ability to form strong pair bonds may thus be constrained by their levels of oxidative damage, with potential downstream effects on fitness

    Defective Lipid Droplet-Lysosome Interaction Causes Fatty Liver Disease as Evidenced by Human Mutations in TMEM199 and CCDC115

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    BACKGROUND & AIMS: Recently, novel inborn errors of metabolism were identified because of mutations in V-ATPase assembly factors TMEM199 and CCDC115. Patients are characterized by generalized protein glycosylation defects, hypercholesterolemia, and fatty liver disease. Here, we set out to characterize the lipid and fatty liver phenotype in human plasma, cell models, and a mouse model. METHODS AND RESULTS: Patients with TMEM199 and CCDC115 mutations displayed hyperlipidemia, characterized by increased levels of lipoproteins in the very low density lipoprotein range. HepG2 hepatoma cells, in which the expression of TMEM199 and CCDC115 was silenced, and induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells from patients with TMEM199 mutations showed markedly increased secretion of apolipoprotein B (apoB) compared with controls. A mouse model for TMEM199 deficiency with a CRISPR/Cas9-mediated knock-in of the human A7E mutation had marked hepatic steatosis on chow diet. Plasma N-glycans were hypogalactosylated, consistent with the patient phenotype, but no clear plasma lipid abnormalities were observed in the mouse model. In the siTMEM199 and siCCDC115 HepG2 hepatocyte models, increased numbers and size of lipid droplets were observed, including abnormally large lipid droplets, which colocalized with lysosomes. Excessive de novo lipogenesis, failing oxidative capacity, and elevated lipid uptake were not observed. Further investigation of lysosomal function revealed impaired acidification combined with impaired autophagic capacity. CONCLUSIONS: Our data suggest that the hypercholesterolemia in TMEM199 and CCDC115 deficiency is due to increased secretion of apoB-containing particles. This may in turn be secondary to the hepatic steatosis observed in these patients as well as in the mouse model. Mechanistically, we observed impaired lysosomal function characterized by reduced acidification, autophagy, and increased lysosomal lipid accumulation. These findings could explain the hepatic steatosis seen in patients and highlight the importance of lipophagy in fatty liver disease. Because this pathway remains understudied and its regulation is largely untargeted, further exploration of this pathway may offer novel strategies for therapeutic interventions to reduce lipotoxicity in fatty liver disease

    Conceptual barriers to progress within evolutionary biology

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    In spite of its success, Neo-Darwinism is faced with major conceptual barriers to further progress, deriving directly from its metaphysical foundations. Most importantly, neo-Darwinism fails to recognize a fundamental cause of evolutionary change, “niche construction”. This failure restricts the generality of evolutionary theory, and introduces inaccuracies. It also hinders the integration of evolutionary biology with neighbouring disciplines, including ecosystem ecology, developmental biology, and the human sciences. Ecology is forced to become a divided discipline, developmental biology is stubbornly difficult to reconcile with evolutionary theory, and the majority of biologists and social scientists are still unhappy with evolutionary accounts of human behaviour. The incorporation of niche construction as both a cause and a product of evolution removes these disciplinary boundaries while greatly generalizing the explanatory power of evolutionary theory

    Characterising the physical and chemical properties of a young Class 0 protostellar core embedded in the Orion B9 filament

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