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Witze A 《Nature》2008,455(7212):442-445
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Ahn S  Joyner AL 《Nature》2005,437(7060):894-897
Sonic hedgehog (Shh) has been implicated in the ongoing neurogenesis in postnatal rodent brains. Here we adopted an in vivo genetic fate-mapping strategy, using Gli1 (GLI-Kruppel family member) as a sensitive readout of Shh activity, to systematically mark and follow the fate of Shh-responding cells in the adult mouse forebrain. We show that initially, only a small population of cells (including both quiescent neural stem cells and transit-amplifying cells) responds to Shh in regions undergoing neurogenesis. This population subsequently expands markedly to continuously provide new neurons in the forebrain. Our study of the behaviour of quiescent neural stem cells provides in vivo evidence that they can self-renew for over a year and generate multiple cell types. Furthermore, we show that the neural stem cell niches in the subventricular zone and dentate gyrus are established sequentially and not until late embryonic stages.  相似文献   
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Cells respond to internal and external cellular stressors by activating stress-response pathways that re-establish homeostasis. If homeostasis is not achieved in a timely manner, stress pathways trigger programmed cell death (apoptosis) to preserve organism integrity. A highly conserved stress pathway is the unfolded protein response (UPR), which senses excessive amounts of unfolded proteins in the ER. While a physiologically beneficial pathway, the UPR requires tight regulation to provide a beneficial outcome and avoid deleterious consequences. Recent work has demonstrated that a conserved and highly selective RNA degradation pathway—nonsense-mediated RNA decay (NMD)—serves as a major regulator of the UPR pathway. NMD degrades mRNAs encoding UPR components to prevent UPR activation in response to innocuous ER stress. In response to strong ER stress, NMD is inhibited by the UPR to allow for a full-magnitude UPR response. Recent studies have indicated that NMD also has other stress-related functions, including promoting the timely termination of the UPR to avoid apoptosis; NMD also regulates responses to non-ER stressors, including hypoxia, amino-acid deprivation, and pathogen infection. NMD regulates stress responses in species across the phylogenetic scale, suggesting that it has conserved roles in shaping stress responses. Stress pathways are frequently constitutively activated or dysregulated in human disease, raising the possibility that “NMD therapy” may provide clinical benefit by downmodulating stress responses.  相似文献   
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Meteorology: bad weather ahead   总被引:1,自引:0,他引:1  
Witze A 《Nature》2006,441(7093):564-566
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Geology: the start of the world as we know it   总被引:1,自引:0,他引:1  
Witze A 《Nature》2006,442(7099):128-131
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High plant diversity is needed to maintain ecosystem services   总被引:3,自引:0,他引:3  
Biodiversity is rapidly declining worldwide, and there is consensus that this can decrease ecosystem functioning and services. It remains unclear, though, whether few or many of the species in an ecosystem are needed to sustain the provisioning of ecosystem services. It has been hypothesized that most species would promote ecosystem services if many times, places, functions and environmental changes were considered; however, no previous study has considered all of these factors together. Here we show that 84% of the 147 grassland plant species studied in 17 biodiversity experiments promoted ecosystem functioning at least once. Different species promoted ecosystem functioning during different years, at different places, for different functions and under different environmental change scenarios. Furthermore, the species needed to provide one function during multiple years were not the same as those needed to provide multiple functions within one year. Our results indicate that even more species will be needed to maintain ecosystem functioning and services than previously suggested by studies that have either (1) considered only the number of species needed to promote one function under one set of environmental conditions, or (2) separately considered the importance of biodiversity for providing ecosystem functioning across multiple years, places, functions or environmental change scenarios. Therefore, although species may appear functionally redundant when one function is considered under one set of environmental conditions, many species are needed to maintain multiple functions at multiple times and places in a changing world.  相似文献   
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