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Institution

University of Virginia

EducationCharlottesville, Virginia, United States
About: University of Virginia is a education organization based out in Charlottesville, Virginia, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 52543 authors who have published 113268 publications receiving 5220506 citations. The organization is also known as: U of V & UVa.


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Journal ArticleDOI
TL;DR: Viral fusion proteins convert from a fusion-competent state to a membrane-embedded homotrimeric prehairpin, and then to a trimer-of-hairpins that brings the fusion peptide and the transmembrane domain into close proximity thereby facilitating the union of viral and target membranes.
Abstract: Recent work has identified three distinct classes of viral membrane fusion proteins based on structural criteria. In addition, there are at least four distinct mechanisms by which viral fusion proteins can be triggered to undergo fusion-inducing conformational changes. Viral fusion proteins also contain different types of fusion peptides and vary in their reliance on accessory proteins. These differing features combine to yield a rich diversity of fusion proteins. Yet despite this staggering diversity, all characterized viral fusion proteins convert from a fusion-competent state (dimers or trimers, depending on the class) to a membrane-embedded homotrimeric prehairpin, and then to a trimer-of-hairpins that brings the fusion peptide, attached to the target membrane, and the transmembrane domain, attached to the viral membrane, into close proximity thereby facilitating the union of viral and target membranes. During these conformational conversions, the fusion proteins induce membranes to progress through stages of close apposition, hemifusion, and then the formation of small, and finally large, fusion pores. Clearly, highly divergent proteins have converged on the same overall strategy to mediate fusion, an essential step in the life cycle of every enveloped virus.

744 citations

Journal ArticleDOI
TL;DR: The fluvial system is a major concern in modeling landform evolution in response to tectonic deformation as discussed by the authors, and sediment routing through alluvial channels must account for supply from slope erosion, transport rates, abrasion, and sorting.
Abstract: The fluvial system is a major concern in modeling landform evolution in response to tectonic deformation. Three stream bed types (bedrock, coarse-bed alluvial, and fine-bed alluvial) differ in factors controlling their occurrence and evolution and in appropriate modeling approaches. Spatial and temporal transitions among bed types occur in response to changes in sediment characteristics and tectonic deformation. Erosion in bedrock channels depends upon the ability to scour or pluck bed material; this detachment capacity is often a power function of drainage area and gradient. Exposure of bedrock in channel beds, due to rapid downcutting or resistant rock, slows the response of headwater catchments to downstream baselevel changes. Sediment routing through alluvial channels must account for supply from slope erosion, transport rates, abrasion, and sorting. In regional landform modeling, implicit rate laws must be developed for sediment production from erosion of sub-grid-scale slopes and small channels.

744 citations

Journal ArticleDOI
TL;DR: Replacement provided a more durable correction of mitral regurgitation, but there was no significant between-group difference in clinical outcomes.
Abstract: Background Ischemic mitral regurgitation is associated with a substantial risk of death. Practice guidelines recommend surgery for patients with a severe form of this condition but acknowledge that the supporting evidence for repair or replacement is limited. Methods We randomly assigned 251 patients with severe ischemic mitral regurgitation to undergo either mitral-valve repair or chordal-sparing replacement in order to evaluate efficacy and safety. The primary end point was the left ventricular end-systolic volume index (LVESVI) at 12 months, as assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized below the lowest LVESVI rank. Results At 12 months, the mean LVESVI among surviving patients was 54.6±25.0 ml per square meter of body-surface area in the repair group and 60.7±31.5 ml per square meter in the replacement group (mean change from baseline, −6.6 and −6.8 ml per square meter, respectively). The rate of death was 14.3% in the repair group and 17.6% in the replacement g...

741 citations

Journal ArticleDOI
01 Apr 2007
TL;DR: In this article, the authors describe previously modeled predictions of ecological change in boreal Alaska, Canada and Russia, and investigate potential evidence of current climate-induced change, and suggest that there is substantial evidence throughout the circumboreal region to conclude that the biosphere within the boreal terrestrial environment has already responded to the transient effects of climate change.
Abstract: For about three decades, there have been many predictions of the potential ecological response in boreal regions to the currently warmer conditions. In essence, a widespread, naturally occurring experiment has been conducted over time. In this paper, we describe previously modeled predictions of ecological change in boreal Alaska, Canada and Russia, and then we investigate potential evidence of current climate-induced change. For instance, ecological models have suggested that warming will induce the northern and upslope migration of the treeline and an alteration in the current mosaic structure of boreal forests. We present evidence of the migration of keystone ecosystems in the upland and lowland treeline of mountainous regions across southern Siberia. Ecological models have also predicted a moisture-stress-related dieback in white spruce trees in Alaska, and current investigations show that as temperatures increase, white spruce tree growth is declining. Additionally, it was suggested that increases in infestation and wildfire disturbance would be catalysts that precipitate the alteration of the current mosaic forest composition. In Siberia, five of the last seven years have resulted in extreme fire seasons, and extreme fire years have also been more frequent in both Alaska and Canada. In addition, Alaska has experienced extreme and geographically expansive multi-year outbreaks of the spruce beetle, which had been previously limited by the cold, moist environment. We suggest that there is substantial evidence throughout the circumboreal region to conclude that the biosphere within the boreal terrestrial environment has already responded to the transient effects of climate change. Additionally, temperature increases and warming-induced change are progressing faster than had been predicted in some regions, suggesting a potential non-linear rapid response to changes in climate, as opposed to the predicted slow linear response to climate change.

741 citations

Journal ArticleDOI
TL;DR: In this paper, localized central and peripheral nervous system expression of three transcripts (α1G, α1H, and α1I) of the T-type calcium channel family (CaVT) was found.
Abstract: Low voltage-activated (T-type) calcium currents are observed in many central and peripheral neurons and display distinct physiological and functional properties. Using in situ hybridization, we have localized central and peripheral nervous system expression of three transcripts (α1G, α1H, and α1I) of the T-type calcium channel family (CaVT). Each mRNA demonstrated a unique distribution, and expression of the three genes was largely complementary. We found high levels of expression of these transcripts in regions associated with prominent T-type currents, including inferior olivary and thalamic relay neurons (which expressed α1G), sensory ganglia, pituitary, and dentate gyrus granule neurons (α1H), and thalamic reticular neurons (α1I and α1H). Other regions of high expression included the Purkinje cell layer of the cerebellum, the bed nucleus of the stria terminalis, the claustrum (α1G), the olfactory tubercles (α1H and α1I), and the subthalamic nucleus (α1I and α1G). Some neurons expressed high levels of all three genes, including hippocampal pyramidal neurons and olfactory granule cells. Many brain regions showed a predominance of labeling for α1G, including the amygdala, cerebral cortex, rostral hypothalamus, brainstem, and spinal cord. Exceptions included the basal ganglia, which showed more prominent labeling for α1H and α1I, and the olfactory bulb, the hippocampus, and the caudal hypothalamus, which showed more even levels of all three transcripts. Our results are consistent with the hypothesis that differential gene expression underlies pharmacological and physiological heterogeneity observed in neuronal T-type calcium currents, and they provide a molecular basis for the study of T-type channels in particular neurons.

741 citations


Authors

Showing all 53083 results

NameH-indexPapersCitations
Joan Massagué189408149951
Michael Rutter188676151592
Gordon B. Mills1871273186451
Ralph Weissleder1841160142508
Gonçalo R. Abecasis179595230323
Jie Zhang1784857221720
John R. Yates1771036129029
John A. Rogers1771341127390
Bradley Cox1692150156200
Mika Kivimäki1661515141468
Hongfang Liu1662356156290
Carl W. Cotman165809105323
Ralph A. DeFronzo160759132993
Elio Riboli1581136110499
Dan R. Littman157426107164
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023189
2022783
20215,565
20205,600
20195,001
20184,586