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41.
The effects of obesity and a high-fat (HF) diet on whole body and tissue-specific metabolism of lactating dams and their offspring were examined in C57/B6 mice. Female mice were fed low-fat (LF) or HF diets before and throughout pregnancy and lactation. HF-fed mice were segregated into lean (HF-Ln) and obese (HF-Ob) groups before pregnancy by their weight gain response. Compared to LF-Ln dams, HF-Ln, and HF-Ob dams exhibited a greater positive energy balance (EB) and increased dietary fat retention in peripheral tissues (P < 0.05). HF-Ob dams had greater dietary fat retention in liver and adipose compared to HF-Ln dams (P < 0.05). De novo synthesized fat was decreased in tissues and milk from HF-fed dams compared to LF-Ln dams (P < 0.05). However, less dietary and de novo synthesized fat was found in the HF-Ob mammary glands compared to HF-Ln (P < 0.05). Obesity was associated with reduced milk triglycerides relative to lean controls (P < 0.05). Compared to HF diet alone obesity has additional adverse affects, impairing both lipid metabolism as well as milk fat production. Growth rates of LF-Ln litters were lower than HF-Ln and HF-Ob litters (P < 0.05). Total energy expenditure (TEE) of HF-Ob litters was reduced relative to HF-Ln litters, whereas their respiratory exchange ratios (RERs) were increased (P < 0.05). Collectively these data show that consumption of a HF diet significantly affects maternal and neonatal metabolism and that maternal obesity can independently alter these responses.  相似文献   
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Proteins of the Leishmania hydrophilic acylated surface protein B (HASPB) family are only expressed in infective parasites (both extra- and intracellular stages) and, together with the peripheral membrane protein SHERP (small hydrophilic endoplasmic reticulum-associated protein), are essential for parasite differentiation (metacyclogenesis) in the sand fly vector. HASPB is a 'non-classically' secreted protein, requiring N-terminal acylation for trafficking to and exposure on the plasma membrane. Here, we use live cell imaging methods to further explore this pathway to the membrane and flagellum. Unlike HASPB trafficking in transfected mammalian cells, we find no evidence for a phosphorylation-regulated recycling pathway in metacyclic parasites. Once at the plasma membrane, HASPB18-GFP (green fluorescent protein) can undergo bidirectional movement within the inner leaflet of the membrane and on the flagellum. Transfer of fluorescent protein between the flagellum and the plasma membrane is compromised, however, suggesting the presence of a diffusion barrier at the base of the Leishmania flagellum. Full-length HASPB is released from the metacyclic parasite surface on to macrophages during phagocytosis but while expression is maintained in intracellular amastigotes, HASPB cannot be detected on the external surface in these cells. Thus HASPB may be a dual function protein that is shed by the infective metacyclic but retained internally once Leishmania are taken up by macrophages.  相似文献   
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BACKGROUND AND OBJECTIVES: Recent experimental evidence from rodent models suggests a potential risk for transmissible spongiform encephalopathy (TSE) transmission by blood. The emergence of a new variant Creutzfeldt-Jakob disease (vCJD) has raised increased concerns about the safety of blood components and plasma products derived from vCJD-infected donors. Recent risk-minimisation strategies have included a ban on the use of UK-sourced plasma for the preparation of licensed blood products and leukodepletion of blood donations for fear of possible transmission of the human TSE via blood or blood components. The aim of this study was to investigate the capability and efficacy of a preparative electrophoresis system (Gradiflow) in the removal of TSE contaminants during the separation of plasma products. MATERIALS AND METHODS: Using hamster adapted scrapie 263 K as a model for TSE agent, albumin and IgG separation from human plasma by Gradiflow were performed separately by spiking a 263 K scrapie microsomal fraction to the feed material at each process step. Samples from pre- and post-Gradiflow separation process were titrated to the end-point for the detection of the disease-associated, proteinase K resistant form of the pathogenic prion protein (PrP(Sc)) by Western blot. RESULTS: Under all conditions tested, a greater than 3 log(10) reduction was achieved with no PrP(Sc) detected in any of the pooled products for either of the IgG or albumin separations. These data show that Gradiflow processing has clear advantages for concurrent purification of plasma products and in-process TSE removal. CONCLUSIONS: Our findings suggest that Gradiflow process is a viable alternative to remove causative TSE agents during plasma products separation, potentially eliminating the risk of TSE agents transmission.  相似文献   
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