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排序方式: 共有185条查询结果,搜索用时 15 毫秒
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Byron Andrews Alan E. Murphy Michele Stofella Sarah Maslen Leonardo Almeida-Souza J. Mark Skehel Nathan G. Skene Frank Sobott René A.W. Frank 《Molecular & cellular proteomics : MCP》2022,21(2):100192
The amount of any given protein in the brain is determined by the rates of its synthesis and destruction, which are regulated by different cellular mechanisms. Here, we combine metabolic labeling in live mice with global proteomic profiling to simultaneously quantify both the flux and amount of proteins in mouse models of neurodegeneration. In multiple models, protein turnover increases were associated with increasing pathology. This method distinguishes changes in protein expression mediated by synthesis from those mediated by degradation. In the AppNL-F knockin mouse model of Alzheimer’s disease, increased turnover resulted from imbalances in both synthesis and degradation, converging on proteins associated with synaptic vesicle recycling (Dnm1, Cltc, Rims1) and mitochondria (Fis1, Ndufv1). In contrast to disease models, aging in wild-type mice caused a widespread decrease in protein recycling associated with a decrease in autophagic flux. Overall, this simple multidimensional approach enables a comprehensive mapping of proteome dynamics and identifies affected proteins in mouse models of disease and other live animal test settings. 相似文献
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In the mammalian cortex, the initial formation of synaptic connections is followed by a prolonged period during which synaptic circuits are functional, but retain an elevated capacity for activity‐dependent remodeling and functional plasticity. During this period, synaptic terminals appear fully mature, morphologically and physiologically. We show here, however, that synaptic terminals during this period are distinguished by their simultaneous accumulation of multiple growth‐associated proteins at levels characteristic of axonal growth cones, and proteins involved in synaptic transmitter release at levels characteristic of adult synapses. We show further that newly formed synapses undergo a switch in the dynamic S‐palmitoylation of proteins early in the critical period, which includes a large and specific decrease in the palmitoylation of GAP‐43 and other major substrates characteristic of growth cones. Previous studies have shown that a similar reduction in ongoing palmitoylation of growth cone proteins is sufficient to stop advancing axons in vitro, suggesting that a developmental switch in protein S‐palmitoylation serves to disengage the molecular machinery for axon extension in the absence of local triggers for remodeling during the critical period. Only much later does a decline in the availability of major growth cone components mark the molecular maturation of cortical synapses at the close of the critical period. © 1999 John Wiley & Sons, Inc. J Neurobiol 39: 423–437, 1999 相似文献
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Skene Keith 《BMJ (Clinical research ed.)》1902,2(2184):1563-1564
87.
Background
In a number of species males damage females during copulation, but the reasons for this remain unclear. It may be that males are trying to manipulate female mating behaviour or their life histories. Alternatively, damage may be a side-effect of male-male competition. In the black scavenger or dung fly Sepsis cynipsea (Diptera: Sepsidae) mating reduces female survival, apparently because males wound females during copulation. However, this damage does not seem to relate to attempted manipulation of female reproduction by males. Here we tested the hypothesis that harming females during mating is an incidental by-product of characters favoured during pre-copulatory male-male competition. We assessed whether males and their sons vary genetically in their ability to obtain matings and harm females, and whether more successful males were also more damaging. We did this by ranking males' mating success in paired competitions across several females whose longevity under starvation was subsequently measured. 相似文献88.
A change in twist of actin provides the force for the extension of the acrosomal process in limulus sperm: the false-discharge reaction 总被引:1,自引:5,他引:1 下载免费PDF全文
One of the most spectacular motions is the generation of the acrosomal process in the limulus sperm. On contact with the egg, the sperm generates a 60-mum-long process that literally drills its way through the jelly surrounding the egg. This irresversible reaction takes only a few seconds. We suggested earlier that this motion is driven by a change in twist of the actin filaments comprising the acrosomal process. In this paper we analyze the so-called false discharge, a reversible reaction, in which the acrosomal filament bundle extends laterally from the base of the sperm and not anteriorly from the apex. Unlike the true discharge, which is straight, the false discharge is helical. Before extension, the filament bundle is coiled about the base of the sperm. In the coil, the bundle is not smoothly bent but consists of arms (straight segments) and elbows (corners) so that the coil looks like a 14-sided polygon. The extension of the false discharge works as follows: starting at the base of the bundle, the filaments change their twist which concomitantly changes the orientations of the elbows relative to each other; that is, in the coil, the elbows all like in a common plane, but after the change in twist, the plane of each elbow is rotated to be perpendicular to that of its neighbors. This change transforms the bundle from a compact coil into an extended left- handed helix. Because the basal end of the bundle is unconstrained, the extension is lateral. The true discharge works the same way but starts at the apical end of the bundle. The apical end, however, is constrained by its passage through the nuclear canal, which directs the extention anteriorly. Unlike the false discharge, during the true discharge the elbows are melted out, making the reaction irreversible. This study shows that rapid movement can be regenerated by actin without myosin and gives us insight into the molecular mechanism. 相似文献
89.
Evolution at the tip and base of the X chromosome in an African population of Drosophila melanogaster 总被引:1,自引:0,他引:1
Hitchhiking effects of advantageous mutations have been invoked to explain
reduced polymorphism in regions of low crossing-over in Drosophila. Besides
reducing DNA heterozygosity, hitchhiking effects should produce strong
linkage disequilibrium and a frequency spectrum skewed toward an excess of
rare polymorphisms (compared to the neutral expectation). We measured DNA
polymorphism in a Zimbabwe population of D. melanogaster at three loci,
yellow, achaete, and suppressor of forked, located in regions of reduced
crossing-over. Similar to previously published surveys of these genomic
regions in other populations, we observed low levels of nucleotide
variability. However, the frequency spectrum was compatible with a neutral
model, and there was abundant evidence for recombination in the history of
the yellow and ac genes. Thus, some aspects of the data cannot be accounted
for by a simple hitchhiking model. An alternative hypothesis, background
selection, might be compatible with the observed patterns of linkage
disequilibrium and the frequency spectrum. However, this model cannot
account for the observed reduction in nucleotide heterozygosity. Thus,
there is currently no satisfactory theoretical model for the data from the
tip and base of the X chromosome in D. melanogaster.
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