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The pH and lumenal environment of intracellular organelles is considered essential for protein sorting and trafficking through the cell. We provide the first evidence that a mammalian NHE sodium (potassium)/proton exchanger, NHE8, plays a key role in the control of protein trafficking and endosome morphology. At steady state, the majority of epitope-tagged NHE8 was found in the trans-Golgi network of HeLa M-cells, but a proportion was also localized to multivesicular bodies (MVBs). Depletion of NHE8 in HeLa M-cells with siRNA resulted in the perturbation of MVB protein sorting, as shown by an increase in epidermal growth factor degradation. Additionally, NHE8-depleted cells displayed striking perinuclear clustering of endosomes and lysosomes, and there was a ninefold increase in the cellular volume taken up by LAMP1/LBPA-positive, dense MVBs. Our data points to a role for the ion exchange activity of NHE8 being required to maintain endosome morphology, as overexpression of a nonfunctional point mutant protein (NHE8 E225Q) resulted in phenotypes similar to those seen after siRNA depletion of endogenous NHE8. Interestingly, we found that depletion of NHE8, despite its function as a sodium (potassium)/proton antiporter, did not affect the overall pH inside dense MVBs.  相似文献   
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The congenitally jaundiced Gunn rat does not conjugate bilirubin but does conjugate bilirubin dimethyl diester. Partial defects in conjugating p-nitrophenol and demethylating aminopyrine are also evident. A proposed mechanism to explain this combination of findings is a defective microsomal membrane. To examine the 'matrix' of Gunn microsomal membranes, hepatic microsomes were isolated from Gunn (jj) and outbred Wistar (JJ) rats and were studied by electron paramagnetic resonance spectroscopy of 7-doxylstearic and 12-doxylstearic acid probes, fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene, glucose-6-phosphatase activity vs. temperature, and lipid analysis. The data indicate several factors related to lipid bilayer order do not differ in microsomes from jj and JJ.  相似文献   
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Listeners consistently perceive approaching sounds to be closer than they actually are and perceptually underestimate the time to arrival of looming sound sources. In a natural environment, this underestimation results in more time than expected to evade or engage the source and affords a “margin of safety” that may provide a selective advantage. However, a key component in the proposed evolutionary origins of the perceptual bias is the appropriate timing of anticipatory motor behaviors. Here we show that listeners with poorer physical fitness respond sooner to looming sounds and with a larger margin of safety than listeners with better physical fitness. The anticipatory perceptual bias for looming sounds is negatively correlated with physical strength and positively correlated with recovery heart rate (a measure of aerobic fitness). The results suggest that the auditory perception of looming sounds may be modulated by the response capacity of the motor system.  相似文献   
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Myelography using pantopaque in greater than usual amount with a variation in technique, which is described, is believed to provide increased accuracy in differential diagnosis and precise localization of lesions in the lumbar spine. The need for multiple space exploration is eliminated and more detailed information concerning the size and shape of lesions is provided as compared to that secured by the use of 3 or 6 cc. of opaque medium and fluoroscopic examination alone. In 53 cases in which lumbar myelography was performed and the diagnosis verified or disproved at operation, there was a 5 per cent diagnostic error in 41 instances in which the method outlined was used, as compared with 17 per cent error in 12 cases in which only 3 or 6 cc. of radiopaque material and fluoroscopy alone were used. The accuracy of the procedure would appear to warrant its use in the evaluation of patients suspected of having abnormalities of the lumbar discs associated with nerve root compression.  相似文献   
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The effects of natural blooms of Heterosigma akashiwo on freshwater-and saltwater-acclimated juvenile chinook salmon were assessed. Rates of fish mortality in the blooms were independent of acclimation of fish to seawater and the ambient oxygen levels, but were dependent on concentration of algae and ambient water temperatures. No pathological abnormality to gills or other internal organs in the fish were evident. Aeration or oxygenation of fish cages did not enhance or inhibit fish survival in a H. akashiwo bloom. Cause of death was considered to be due to a labile ichthyotoxic agent.  相似文献   
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Exotic (nonnative) species are known to have a wide variety of impacts on native biota. One potential set of impacts that have been poorly studied are the effects of replacing native habitat-providing species with exotic ones, e.g. when native trees that compose a woodland are replaced by an exotic tree plantation. Here we develop a graphical model that can be used to explore how multiple taxonomic components (such as birds, mammals and plants) respond to such changes. We suggest that four categorical responses are possible, with respect to changes in species richness (or other quantitative measures) of taxonomic groups within species assemblages. First, that each taxonomic group compared between habitats will be relatively unchanged, e.g. have equivalent values of species richness. Second, that a decrease (for example in species richness) of one group will be compensated for by an increase (in species richness) of another group. Third, that one or more groups will decrease without any compensated increases in other groups. Fourth, that one or more groups will increase without any compensated decreases in other groups. We provide empirical support for 3 of these 4 responses, with respect to measures of species richness, with much evidence for equivalency between habitats. These types of comparisons should provide a valuable tool for evaluating 1) the efficacy of environmental mitigation efforts that artificially create or restore habitats and 2) the types of changes that have occurred over time or across space as native habitat-producing species are replaced by exotic ones. Finally, this conceptual framework should help to broaden the range of possible changes considered by ecologists who study the impacts of exotic species.  相似文献   
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