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41.
MYO1C, a single-headed class I myosin, associates with cholesterol-enriched lipid rafts and facilitates their recycling from intracellular compartments to the cell surface. Absence of functional MYO1C disturbs the cellular distribution of lipid rafts, causes the accumulation of cholesterol-enriched membranes in the perinuclear recycling compartment, and leads to enlargement of endolysosomal membranes. Several feeder pathways, including classical endocytosis but also the autophagy pathway, maintain the health of the cell by selective degradation of cargo through fusion with the lysosome. Here we show that loss of functional MYO1C leads to an increase in total cellular cholesterol and its disrupted subcellular distribution. We observe an accumulation of autophagic structures caused by a block in fusion with the lysosome and a defect in autophagic cargo degradation. Interestingly, the loss of MYO1C has no effect on degradation of endocytic cargo such as EGFR, illustrating that although the endolysosomal compartment is enlarged in size, it is functional, contains active hydrolases, and the correct pH. Our results highlight the importance of correct lipid composition in autophagosomes and lysosomes to enable them to fuse. Ablating MYO1C function causes abnormal cholesterol distribution, which has a major selective impact on the autophagy pathway.  相似文献   
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In neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis, neuroinflammation can lead to blood‐brain barrier (BBB) breakdown. After intravenous or intra‐arterial injection into mice, endothelial progenitor cells (EPCs) home to the damaged BBB to promote neurovascular repair. Autologous EPCs transfected to express specific therapeutic proteins offer an innovative therapeutic option. Here, we demonstrate that EPC transfection by electroporation with plasmids encoding the reporter protein GFP or an anti‐β‐amyloid antibody fragment (Fab) leads to secretion of each protein. We also demonstrate the secreted anti‐β‐amyloid Fab protein functions in β‐amyloid aggregate solubilization.  相似文献   
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Ecosystems - Ecotones can form hot spots of biodiversity by containing species from multiple ecosystems. Because biodiversity is often linked to ecological function, we posit that rates of key...  相似文献   
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Wetlands Ecology and Management - Oil sands exploration activities across the Alberta boreal peatlands requires tree clearing and results in sites being left compressed and with altered understory...  相似文献   
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Gastrointestinal (GI) helminths are common parasites of humans, wildlife, and livestock, causing chronic infections. In humans and wildlife, poor nutrition or limited resources can compromise an individual''s immune response, predisposing them to higher helminth burdens. This relationship has been tested in laboratory models by investigating infection outcomes following reductions of specific nutrients. However, much less is known about how diet supplementation can impact susceptibility to infection, acquisition of immunity, and drug efficacy in natural host–helminth systems. We experimentally supplemented the diet of wood mice (Apodemus sylvaticus) with high-quality nutrition and measured resistance to the common GI nematode Heligmosomoides polygyrus. To test whether diet can enhance immunity to reinfection, we also administered anthelmintic treatment in both natural and captive populations. Supplemented wood mice were more resistant to H. polygyrus infection, cleared worms more efficiently after treatment, avoided a post-treatment infection rebound, produced stronger general and parasite-specific antibody responses, and maintained better body condition. In addition, when applied in conjunction with anthelmintic treatment, supplemented nutrition significantly reduced H. polygyrus transmission potential. These results show the rapid and extensive benefits of a well-balanced diet and have important implications for both disease control and wildlife health under changing environmental conditions.  相似文献   
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Understanding how landscape change influences the distribution and densities of species, and the consequences of these changes, is a central question in modern ecology. The distribution of white-tailed deer (Odocoileus virginianus) is expanding across North America, and in some areas, this pattern has led to an increase in predators and consequently higher predation rates on woodland caribou (Rangifer tarandus caribou)—an alternate prey species that is declining across western Canada. Understanding the factors influencing deer distribution has therefore become important for effective conservation of caribou in Canada. Changing climate and anthropogenic landscape alteration are hypothesized to facilitate white-tailed deer expansion. Yet, climate and habitat alteration are spatiotemporally correlated, making these factors difficult to isolate. Our study evaluates the relative effects of snow conditions and human-modified habitat (habitat alteration) across space on white-tailed deer presence and relative density. We modeled deer response to snow depth and anthropogenic habitat alteration across a large latitudinal gradient (49° to 60°) in Alberta, Canada, using motion-sensitive camera data collected in winter and spring from 2015 to 2019. Deer distribution in winter and spring were best explained by models including both snow depth and habitat alteration. Sites with shallower snow had higher deer presence regardless of latitude. Increased habitat alteration increased deer presence in the northern portion of the study area only. Winter deer density was best explained by snow depth only, whereas spring density was best explained by both habitat alteration and the previous winter's snow depth. Our results suggest that limiting future habitat alteration or restoring habitat can alter deer distribution, thereby potentially slowing or reversing expansion, but that climate plays a significant role beyond what managers can influence. © 2020 The Wildlife Society.  相似文献   
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Oat (Avena sativa L.) seed is a rich resource of beneficial lipids, soluble fiber, protein, and antioxidants, and is considered a healthful food for humans. Little is known regarding the genetic controllers of variation for these compounds in oat seed. We characterized natural variation in the mature seed metabolome using untargeted metabolomics on 367 diverse lines and leveraged this information to improve prediction for seed quality traits. We used a latent factor approach to define unobserved variables that may drive covariance among metabolites. One hundred latent factors were identified, of which 21% were enriched for compounds associated with lipid metabolism. Through a combination of whole-genome regression and association mapping, we show that latent factors that generate covariance for many metabolites tend to have a complex genetic architecture. Nonetheless, we recovered significant associations for 23% of the latent factors. These associations were used to inform a multi-kernel genomic prediction model, which was used to predict seed lipid and protein traits in two independent studies. Predictions for 8 of the 12 traits were significantly improved compared to genomic best linear unbiased prediction when this prediction model was informed using associations from lipid-enriched factors. This study provides new insights into variation in the oat seed metabolome and provides genomic resources for breeders to improve selection for health-promoting seed quality traits. More broadly, we outline an approach to distill high-dimensional “omics” data to a set of biologically meaningful variables and translate inferences on these data into improved breeding decisions.  相似文献   
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