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Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Neuronal vacuolization and glial activation are pathologic hallmarks in the superoxide dismutase 1 (SOD1) mouse model of ALS. Previously, we found the neuropeptide calcitonin gene-related peptide (CGRP) associated with vacuolization and astrogliosis in the spinal cord of these mice. We now show that CGRP abundance positively correlated with the severity of astrogliosis, but not vacuolization, in several motor and non-motor areas throughout the brain. SOD1 mice harboring a genetic depletion of the βCGRP isoform showed reduced CGRP immunoreactivity associated with vacuolization, while motor functions, body weight, survival, and astrogliosis were not altered. When CGRP signaling was completely disrupted through genetic depletion of the CGRP receptor component, receptor activity-modifying protein 1 (RAMP1), hind limb muscle denervation, and loss of muscle performance were accelerated, while body weight and survival were not affected. Dampened neuroinflammation, i.e., reduced levels of astrogliosis in the brain stem already in the pre-symptomatic disease stage, and reduced microgliosis and lymphocyte infiltrations during the late disease phase were additional neuropathology features in these mice. On the molecular level, mRNA expression levels of brain-derived neurotrophic factor (BDNF) and those of the anti-inflammatory cytokine interleukin 6 (IL-6) were elevated, while those of several pro-inflammatory cytokines found reduced in the brain stem of RAMP1-deficient SOD1 mice at disease end stage. Our results thus identify an important, possibly dual role of CGRP in ALS pathogenesis.  相似文献   
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This article analyses the Danish 1909 celebrations of the centenary of Charles Darwin's birth on 12 February 1809. I argue that the 1909 meetings, lectures and publications devoted to Darwin and his theory of evolution by natural selection can be characterised by ambivalence: on the one hand, tribute to a great man of science who established a new view of nature and, on the other hand, scepticism towards the Darwinian mechanism of natural selection and the wider religious and political implications drawn from his theory. The article examines both professional and popular commemorative activities, focusing primarily on celebratory articles carried in widely circulated magazines and newspapers. I identify three types of interpretations of Darwin's ideas which I characterise as ‘radical’, ‘evangelical’ and ‘safe’ science. These different positions were closely linked to the political and cultural divisions of the periodical press. Moreover, my analysis of the popular press offers a solid basis for asserting that to most people Darwinism was associated with human evolution, primarily the relationship between man and apes, while more sophisticated discussions about the crisis of Darwinism prominent among naturalists played only a secondary role in the public arena. This article demonstrates the value of using newspapers as historical sources when looking for public images of Darwin, popular receptions of Darwinism and representations of science in general.  相似文献   
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Summary Ginkgo biloba extract is known to be efficient in diseases associated with free radical generation. The purpose of this work was to study, under in vitro conditions, the action ofGinkgo biloba extract (Gbe) against superoxide anion ( ), which is directly or indirectly implicated in cell damage.Gbe appears to have both an scavenging effect and also a superoxide dismutase activity. Its antiradical effect was demonstrated by low temperature electron spin resonance and in a non-enzymatic system (phenazine methosulfate-NADH), and its enzymatic activity was shown by polarographic determination.  相似文献   
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As computer science enrollments continue to surge, assessments that involve student collaboration may play a more critical role in improving student learning. We provide a review on some of the most commonly adopted collaborative assessments in computer science, including pair programming, collaborative exams, and group projects. Existing research on these assessment formats is categorized and compared. We also discuss potential future research topics on the aforementioned collaborative assessment formats.  相似文献   
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The author deals with the operational core oflogic, i.e. its diverse procedures ofinference, in order to show that logicallyfalse inferences may in fact be right because –in contrast to logical rationality – theyactually enlarge our knowledge of the world.This does not only mean that logically trueinferences say nothing about the world, butalso that all our inferences are inventedhypotheses the adequacy of which cannot beproved within logic but only pragmatically. Inconclusion the author demonstrates, through therelationship between rule-following andrationality, that it is most irrational to wantto exclude the irrational: it may, at times, bemost rational to think and infer irrationally.Focussing on the operational aspects of knowingas inferring does away with the hiatus betweenlogic and life, cognition and the world(reality) – or whatever other dualism one wantsto invoke –: knowing means inferring, inferringmeans rule-governed interpreting, interpretingis a constructive, synthetic act, and aconstruction that proves adequate (viable) inthe ``world of experience', in life, in thepraxis of living, is, to the constructivistmind, knowledge. It is the practice of livingwhich provides the orienting standards forconstructivist thinking and its judgments ofviability. The question of truth is replaced bythe question of viability, and viabilitydepends on the (right) kind of experiential fit.  相似文献   
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In the present investigation, both static and dynamic precipitations of an Al–Mg–Si–Cu aluminum alloy after solid-solution treatment(SST)were comparatively analyzed using differential scanning calorimetry(DSC). Dynamic aging was performed in the SST alloy through equal channel angular pressing(ECAP) at different temperatures of room temperature, 110, 170, 191 and 300 1C. For comparison, static artificial aging was conducted in the SST alloy at 191 1C with two aging times of 4 and 10 h. The DSC analyses reveal that the dynamic precipitation has occurred in the ECAPed samples, while the activation energies associated with the strengthening precipitates in the dynamic samples are considerably higher than the energies in the SST and static aged samples. The higher activation energies are probably attributed to the smaller grains and higher dislocation density developed after ECAP. The results in the present investigation allow the prediction of the type of the dynamic precipitates to influence the strength of the ultrafine grained alloy during ECAP at various temperatures.  相似文献   
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The chemical composition of the Bannock basin has been studied in some detail. We recently showed that unusual microbial populations, including a new division of Archaea (MSBL1), inhabit the NaCl-rich hypersaline brine. High salinities tend to reduce biodiversity, but when brines come into contact with fresher water the natural haloclines formed frequently contain gradients of other chemicals, including permutations of electron donors and acceptors, that may enhance microbial diversity, activity and biogeochemical cycling. Here we report a 2.5-m-thick chemocline with a steep NaCl gradient at 3.3 km within the water column betweeen Bannock anoxic hypersaline brine and overlying sea water. The chemocline supports some of the most biomass-rich and active microbial communities in the deep sea, dominated by Bacteria rather than Archaea, and including four major new divisions of Bacteria. Significantly higher metabolic activities were measured in the chemocline than in the overlying sea water and underlying brine; functional analyses indicate that a range of biological processes is likely to occur in the chemocline. Many prokaryotic taxa, including the phylogenetically new groups, were confined to defined salinities, and collectively formed a diverse, sharply stratified, deep-sea ecosystem with sufficient biomass to potentially contribute to organic geological deposits.  相似文献   
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