20 research outputs found

    Intoxicação por monofluoroacetato em animais

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    Banking Sector Fragility and the Transmission of Currency Crises

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    We assess whether, complementary to trade and financial linkages, banking sector fragility helps explain the transmission of currency crises. We attempt to strike a balance between the precision of measurement of banking sector fragility on the one hand and its consistent measurement across various crisis episodes on the other. We find that while the role of trade and financial linkages is robust over time, the independent role of banking sector fragility is rather weak and unstable across crisis episodes. Consequently it is difficult to extrapolate observed banking fragility transmission channels from one crisis to another. As a corollary we cannot conclude that during future crisis episodes economies characterized by fragile banking sectors are more prone to crisis transmission

    Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function

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    Gene targeting in mice was used to investigate the unknown function of Scp2, encoding sterol carrier protein-2 (SCP2; a peroxisomal lipid carrier) and sterol carrier protein-x (SCPx; a fusion protein between SCP2 and a peroxisomal thiolase). Complete deficiency of SCP2 and SCPx was associated with marked alterations in gene expression, peroxisome proliferation, hypolipidemia, impaired body weight control, and neuropathy. Along with these abnormalities, catabolism of methyl-branched fatty acyl CoAs was impaired. The defect became evident from up to 10-fold accumulation of the tetramethyl-branched fatty acid phytanic acid in Scp2(−/−) mice. Further characterization supported that the gene disruption led to inefficient import of phytanoyl-CoA into peroxisomes and to defective thiolytic cleavage of 3-ketopristanoyl-CoA. These results corresponded to high-affinity binding of phytanoyl-CoA to the recombinant rat SCP2 protein, as well as high 3-ketopristanoyl-CoA thiolase activity of the recombinant rat SCPx protein

    Mechanical behaviour of copper 15% volume niobium microcomposite wires

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    Cu-Nb microcomposites are attractive in magnet pulsed field technology applications due to their anomalous mechanism of mechanical strength and high electrical conductivity. In this sense, recently it was conceived the use of Cu 15% vol. Nb wires to operate as a high tensile strength cable for a diamond cutting tool (diamond wires) for marble and granite slabbing. The multifilamentary Cu 15% vol. Nb composite was obtained using a new processing route, starting with niobium bars bundled into copper tubes, without arc melting. Cold working techniques, such as swaging and wire drawing, combined with heat treatments such as sintering and annealing, and tube restacking were employed. The tensile property of the composite was measured as a function of the niobium filaments dimensions and morphology into the copper matrix, in the several processing steps. An ultimate tensile strength (UTS) of 960 MPa was obtained for an areal reduction (R = Ao/A, with Ao-initial cross section area, and A-final cross section area) of 4x10(8) X, in which the niobium filaments reached thickness less than 20 nm. The anomalous mechanical strength increase is attributed to the fact that the niobium filaments acts as a barrier to copper dislocations

    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
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