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61.
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Wei-hui Wu Qian Liu Xun Sun Ji-sheng Yu De-sheng Zhao Ye-ping Yu Jun-jie Luo Jia Hu Zhi-wu Yu Yu-fen Zhao Yan-mei Li 《Biochemical and biophysical research communications》2013
Amyloid-β (Aβ) peptides can exist in distinct forms including monomers, oligomers and fibrils, consisting of increased numbers of monomeric units. Among these, Aβ oligomers are implicated as the primary toxic species as pointed by multiple lines of evidence. It has been suggested that toxicity could be rendered by the soluble higher-molecular-weight (high-n) Aβ oligomers. Yet, the most culpable form in the pathogenesis of Alzheimer’s disease (AD) remains elusive. Moreover, the potential interaction among the insoluble fibrils that have been excluded from the responsible aggregates in AD development, Aβ monomers and high-n oligomers is undetermined. Here, we report that insoluble Aβ fibrillar seeds can interact with Aβ monomers at the stoichiometry of 1:2 (namely, each Aβ molecule of seed can bind to two Aβ monomers at a time) facilitating the fibrillization by omitting the otherwise mandatory formation of the toxic high-n oligomers during the fibril maturation. As a result, the addition of exogenous Aβ fibrillar seeds is seen to rescue neuronal cells from Aβ cytotoxicity presumably exerted by high-n oligomers, suggesting an unexpected protective role of Aβ fibrillar seeds. 相似文献
63.
Transmission events are the fundamental building blocks of the dynamics of any infectious disease. Much about the epidemiology of a disease can be learned when these individual transmission events are known or can be estimated. Such estimations are difficult and generally feasible only when detailed epidemiological data are available. The genealogy estimated from genetic sequences of sampled pathogens is another rich source of information on transmission history. Optimal inference of transmission events calls for the combination of genetic data and epidemiological data into one joint analysis. A key difficulty is that the transmission tree, which describes the transmission events between infected hosts, differs from the phylogenetic tree, which describes the ancestral relationships between pathogens sampled from these hosts. The trees differ both in timing of the internal nodes and in topology. These differences become more pronounced when a higher fraction of infected hosts is sampled. We show how the phylogenetic tree of sampled pathogens is related to the transmission tree of an outbreak of an infectious disease, by the within-host dynamics of pathogens. We provide a statistical framework to infer key epidemiological and mutational parameters by simultaneously estimating the phylogenetic tree and the transmission tree. We test the approach using simulations and illustrate its use on an outbreak of foot-and-mouth disease. The approach unifies existing methods in the emerging field of phylodynamics with transmission tree reconstruction methods that are used in infectious disease epidemiology. 相似文献
64.
Kitaru Suda Slawomir Filipek Krzysztof Palczewski Andreas Engel 《Molecular membrane biology》2013,30(6):435-446
Rhodopsin, the prototypical G-protein-coupled receptor, which is densely packed in the disc membranes of rod outer segments, was proposed to function as a monomer. However, a growing body of evidence indicates dimerization and oligomerization of numerous G-protein-coupled receptors, and atomic force microscopy images revealed rows of rhodopsin dimers in murine disc membranes. In this work we demonstrate by electron microscopy of negatively stained samples, blue native- and sodium dodecyl sulphate-polyacrylamide gel electrophoresis, chemical crosslinking, and by proteolysis that native bovine rhodopsin exists mainly as dimers and higher oligomers. These results corroborate the recent findings from atomic force microscopy and molecular modeling on the supramolecular structure and packing arrangement of murine rhodopsin dimers. 相似文献
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In mammals, expression of UBE3A is epigenetically regulated in neurons and expression is restricted to the maternal copy of UBE3A. A recent report claimed that Drosophila melanogaster UBE3A homolog (Dube3a) is preferentially expressed from the maternal allele in fly brain, inferring an imprinting mechanism. However, complex epigenetic regulatory features of the mammalian imprinting center are not present in Drosophila, and allele specific expression of Dube3a has not been documented. We used behavioral and electrophysiological analysis of the Dube3a loss-of-function allele (Dube3a15b) to investigate Dube3a imprinting in fly neurons. We found that motor impairment (climbing ability) and a newly-characterized defect in synaptic transmission are independent of parental inheritance of the Dube3a15b allele. Furthermore, expression analysis of coding single nucleotide polymorphisms (SNPs) in Dube3a did not reveal allele specific expression differences among reciprocal crosses. These data indicate that Dube3a is neither imprinted nor preferentially expressed from the maternal allele in fly neurons. 相似文献
67.
We have previously reported that oxytocin produces an inward current at a holding potential of ?70 mV without a change in glutamatergic excitatory transmission in adult male rat spinal lamina II (substantia gelatinosa; SG) neurons that play a pivotal role in regulating nociceptive transmission. Oxytocin also enhanced GABAergic and glycinergic spontaneous inhibitory transmissions in a manner sensitive to a voltage-gated Na+-channel blocker tetrodotoxin. These actions were mediated by oxytocin-receptor activation. Such a result was different from that obtained by other investigators in young male rat superficial dorsal horn neurons in which an oxytocin-receptor agonist enhanced glutamatergic and GABAergic but not glycinergic spontaneous transmissions. In order to know a developmental change and also sexual difference in the actions of oxytocin, we examined its effect on spontaneous synaptic transmission in adult female and young male rat SG neurons by using the whole-cell patch-clamp technique in spinal cord slices. In adult female rats, oxytocin produced an inward current at ?70 mV without a change in excitatory transmission. GABAergic and glycinergic transmissions were enhanced by oxytocin, the duration of which enhancement was much shorter than in adult male rats. In young (11–21 postnatal days) male rats, oxytocin produced not only an inward but also outward current at ?70 mV, and presynaptically inhibited or facilitated excitatory transmission, depending on the neurons tested; both GABAergic and glycinergic transmissions were enhanced by oxytocin. The inhibitory transmission enhancements in adult female and young male rats were sensitive to tetrodotoxin. Although the data may not be enough to be estimated, it is suggested that synaptic modulation by oxytocin in SG neurons, i.e., cellular mechanism for its antinociceptive action, exhibits a developmental change and sexual difference. 相似文献
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69.
Migration (seasonal round-trip movement across relatively large distances) is common within the animal kingdom. This behaviour often incurs extreme costs in terms of time, energy, and/or survival. Climate, food, predation, and breeding are typically suggested as factors favouring the evolution of migration. Although disease regulation has also been considered, few studies consider it as the primary selective pressure for migration. Our aim was to determine, theoretically, under what conditions migration could reduce the long-term disease prevalence within a population, assuming the only benefits of migration are infection-related. We created two mathematical models, one where the population migrates annually and one where the entire population remains on the breeding ground year-round. In each we simulated disease transmission (frequency-dependent and density-dependent) and quantified eventual disease prevalence. In the migration model we varied the time spent migrating, disease-related migration mortality, and the overall migration mortality. When we compared results from the two models, we found that migration generally lowered disease prevalence. We found a population was healthier if it: (1) spent more time migrating (assuming no disease transmission during migration), (2) had higher disease-induced migration mortality, and (3) had an overall higher mortality when migrating (compared to not migrating). These results provide support for two previously proposed mechanisms by which migration can reduce disease prevalence (migratory escape and migratory cull), and also demonstrate that non-selective mortality during migration is a third mechanism. Our findings indicate that migration may be evolutionarily advantageous even if the only migratory benefit is disease control. 相似文献
70.
Direct exposure to stimuli in their environment is not the only way that animals learn about important information. Individuals can infer fear from a social context through observation. Like humans, rats are very social animals, and may learn to infer information about their environment through their interactions with conspecifics. Here, we first review different models for social transmission of information in rodents. Second, we examine different modes of communication that are important to social learning. Then, we cover the different proximate factors that are thought to modulate the social transmission of information. Next, we identify social and environmental conditions that impact social learning, and finally, we conclude by revisiting social transmission through the lens of the Tinbergen framework. 相似文献