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ConclusionsLower inoculation of RRV-induced progressive liver injury and fibrosis via NK cells. These findings point to the potential use of NK cell-depleting strategies to block progression of liver disease in biliary atresia.  相似文献   
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Airway basal cells (BC) function as stem/progenitor cells capable of differentiating into the luminal ciliated and secretory cells to replenish the airway epithelium during physiological turnover and repair. The objective of this study was to define the role of Notch signaling in regulating human airway BC differentiation into a pseudostratified mucociliated epithelium. Notch inhibition with γ-secretase inhibitors demonstrated Notch activation is essential for BC differentiation into secretory and ciliated cells, but more so for the secretory lineage. Sustained cell autonomous ligand independent Notch activation via lentivirus expression of the intracellular domain of each Notch receptor (NICD1-4) demonstrated that the NOTCH2 and 4 pathways have little effect on BC differentiation into secretory and ciliated cells, while activation of the NOTCH1 or 3 pathways has a major influence, with persistent expression of NICD1 or 3 resulting in a skewing toward secretory cell differentiation with a parallel decrease in ciliated cell differentiation. These observations provide insights into the control of the balance of BC differentiation into the secretory vs ciliated cell lineage, a balance that is critical for maintaining the normal function of the airway epithelium in barrier defense against the inhaled environment.  相似文献   
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Multiple stressors threaten stream physical and biological quality, including elevated nutrients and other contaminants, riparian and in-stream habitat degradation and altered natural flow regime. Unconventional oil and gas (UOG) development is one emerging stressor that spans the U.S. UOG development could alter stream sedimentation, riparian extent and composition, in-stream flow, and water quality. We developed indices to describe the watershed sensitivity and exposure to natural and anthropogenic disturbances and computed a vulnerability index from these two scores across stream catchments in six productive shale plays. We predicted that catchment vulnerability scores would vary across plays due to climatic, geologic and anthropogenic differences. Across-shale averages supported this prediction revealing differences in catchment sensitivity, exposure, and vulnerability scores that resulted from different natural and anthropogenic environmental conditions. For example, semi-arid Western shale play catchments (Mowry, Hilliard, and Bakken) tended to be more sensitive to stressors due to low annual average precipitation and extensive grassland. Catchments in the Barnett and Marcellus-Utica were naturally sensitive from more erosive soils and steeper catchment slopes, but these catchments also experienced areas with greater UOG densities and urbanization. Our analysis suggested Fayetteville and Barnett catchments were vulnerable due to existing anthropogenic exposure. However, all shale plays had catchments that spanned a wide vulnerability gradient. Our results identify vulnerable catchments that can help prioritize stream protection and monitoring efforts. Resource managers can also use these findings to guide local development activities to help reduce possible environmental effects.  相似文献   
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Climate change is a major threat to global biodiversity, and its impacts can act synergistically to heighten the severity of other threats. Most research on projecting species range shifts under climate change has not been translated to informing priority management strategies on the ground. We develop a prioritization framework to assess strategies for managing threats to biodiversity under climate change and apply it to the management of invasive animal species across one‐sixth of the Australian continent, the Lake Eyre Basin. We collected information from key stakeholders and experts on the impacts of invasive animals on 148 of the region's most threatened species and 11 potential strategies. Assisted by models of current distributions of threatened species and their projected distributions, experts estimated the cost, feasibility, and potential benefits of each strategy for improving the persistence of threatened species with and without climate change. We discover that the relative cost‐effectiveness of invasive animal control strategies is robust to climate change, with the management of feral pigs being the highest priority for conserving threatened species overall. Complementary sets of strategies to protect as many threatened species as possible under limited budgets change when climate change is considered, with additional strategies required to avoid impending extinctions from the region. Overall, we find that the ranking of strategies by cost‐effectiveness was relatively unaffected by including climate change into decision‐making, even though the benefits of the strategies were lower. Future climate conditions and impacts on range shifts become most important to consider when designing comprehensive management plans for the control of invasive animals under limited budgets to maximize the number of threatened species that can be protected.  相似文献   
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Background and Aims Conservation of the genetic diversity afforded by recalcitrant seeds is achieved by cryopreservation, in which excised embryonic axes (or, where possible, embryos) are treated and stored at temperatures lower than −180 °C using liquid nitrogen. It has previously been shown that intracellular ice forms in rapidly cooled embryonic axes of Acer saccharinum (silver maple) but this is not necessarily lethal when ice crystals are small. This study seeks to understand the nature and extent of damage from intracellular ice, and the course of recovery and regrowth in surviving tissues.Methods Embryonic axes of A. saccharinum, not subjected to dehydration or cryoprotection treatments (water content was 1·9 g H2O g−1 dry mass), were cooled to liquid nitrogen temperatures using two methods: plunging into nitrogen slush to achieve a cooling rate of 97 °C s−1 or programmed cooling at 3·3 °C s−1. Samples were thawed rapidly (177 °C s−1) and cell structure was examined microscopically immediately, and at intervals up to 72 h in vitro. Survival was assessed after 4 weeks in vitro. Axes were processed conventionally for optical microscopy and ultrastructural examination.Key Results Immediately following thaw after cryogenic exposure, cells from axes did not show signs of damage at an ultrastructural level. Signs that cells had been damaged were apparent after several hours of in vitro culture and appeared as autophagic decomposition. In surviving tissues, dead cells were sloughed off and pockets of living cells were the origin of regrowth. In roots, regrowth occurred from the ground meristem and procambium, not the distal meristem, which became lethally damaged. Regrowth of shoots occurred from isolated pockets of surviving cells of peripheral and pith meristems. The size of these pockets may determine the possibility for, the extent of and the vigour of regrowth.Conclusions Autophagic degradation and ultimately autolysis of cells following cryo-exposure and formation of small (0·2–0·4 µm) intracellular ice crystals challenges current ideas that ice causes immediate physical damage to cells. Instead, freezing stress may induce a signal for programmed cell death (PCD). Cells that form more ice crystals during cooling have faster PCD responses.  相似文献   
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