Institution
Utrecht University
Education•Utrecht, Utrecht, Netherlands•
About: Utrecht University is a education organization based out in Utrecht, Utrecht, Netherlands. It is known for research contribution in the topics: Population & Poison control. The organization has 58176 authors who have published 139351 publications receiving 6214282 citations. The organization is also known as: UU & Universiteit Utrecht.
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TL;DR: Severe disruption of Fam134b in mice causes expansion of the ER, inhibits ER turnover, sensitizes cells to stress-induced apoptotic cell death and leads to degeneration of sensory neurons, so selective ER-phagy via FAM134 proteins is indispensable for mammalian cell homeostasis and controls ER morphology and turnover in mice and humans.
Abstract: The endoplasmic reticulum (ER) is the largest intracellular endomembrane system, enabling protein and lipid synthesis, ion homeostasis, quality control of newly synthesized proteins and organelle communication. Constant ER turnover and modulation is needed to meet different cellular requirements and autophagy has an important role in this process. However, its underlying regulatory mechanisms remain unexplained. Here we show that members of the FAM134 reticulon protein family are ER-resident receptors that bind to autophagy modifiers LC3 and GABARAP, and facilitate ER degradation by autophagy ('ER-phagy'). Downregulation of FAM134B protein in human cells causes an expansion of the ER, while FAM134B overexpression results in ER fragmentation and lysosomal degradation. Mutant FAM134B proteins that cause sensory neuropathy in humans are unable to act as ER-phagy receptors. Consistently, disruption of Fam134b in mice causes expansion of the ER, inhibits ER turnover, sensitizes cells to stress-induced apoptotic cell death and leads to degeneration of sensory neurons. Therefore, selective ER-phagy via FAM134 proteins is indispensable for mammalian cell homeostasis and controls ER morphology and turnover in mice and humans.
662 citations
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National Center for Atmospheric Research1, Lawrence Berkeley National Laboratory2, Oak Ridge National Laboratory3, Utrecht University4, Columbia University5, Chinese Academy of Sciences6, University of Houston7, California Institute of Technology8, University of California, Los Angeles9, Institute of Arctic and Alpine Research10, Los Alamos National Laboratory11, Harvard University12, Cooperative Institute for Research in Environmental Sciences13, University of Arizona14, University of Colorado Boulder15, Purdue University16, Michigan State University17, Argonne National Laboratory18, University of Michigan19, Auburn University20, Pacific Northwest National Laboratory21, Goddard Space Flight Center22, University of California, Irvine23, Virginia Tech24, University of Sheffield25
TL;DR: The Community Land Model (CLM) is the land component of the Community Earth System Model (CESM) and is used in several global and regional modeling systems.
Abstract: The Community Land Model (CLM) is the land component of the Community Earth System Model (CESM) and is used in several global and regional modeling systems. In this paper, we introduce model developments included in CLM version 5 (CLM5), which is the default land component for CESM2. We assess an ensemble of simulations, including prescribed and prognostic vegetation state, multiple forcing data sets, and CLM4, CLM4.5, and CLM5, against a range of metrics including from the International Land Model Benchmarking (ILAMBv2) package. CLM5 includes new and updated processes and parameterizations: (1) dynamic land units, (2) updated parameterizations and structure for hydrology and snow (spatially explicit soil depth, dry surface layer, revised groundwater scheme, revised canopy interception and canopy snow processes, updated fresh snow density, simple firn model, and Model for Scale Adaptive River Transport), (3) plant hydraulics and hydraulic redistribution, (4) revised nitrogen cycling (flexible leaf stoichiometry, leaf N optimization for photosynthesis, and carbon costs for plant nitrogen uptake), (5) global crop model with six crop types and time‐evolving irrigated areas and fertilization rates, (6) updated urban building energy, (7) carbon isotopes, and (8) updated stomatal physiology. New optional features include demographically structured dynamic vegetation model (Functionally Assembled Terrestrial Ecosystem Simulator), ozone damage to plants, and fire trace gas emissions coupling to the atmosphere. Conclusive establishment of improvement or degradation of individual variables or metrics is challenged by forcing uncertainty, parametric uncertainty, and model structural complexity, but the multivariate metrics presented here suggest a general broad improvement from CLM4 to CLM5.
661 citations
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TL;DR: In this article, the authors take a first step towards an extended, interdisciplinary policy mix concept based on a review of the bodies of literature on innovation studies, environmental economics and policy analysis.
661 citations
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TL;DR: It is shown that city-specific per-capita excess mortality in 1918 was significantly correlated with 1917 per-Capita mortality, indicating some intrinsic variation in overall mortality, perhaps related to sociodemographic factors.
Abstract: During the 1918 influenza pandemic, the U.S., unlike Europe, put considerable effort into public health interventions. There was also more geographic variation in the autumn wave of the pandemic in the U.S. compared with Europe, with some cities seeing only a single large peak in mortality and others seeing double-peaked epidemics. Here we examine whether differences in the public health measures adopted by different cities can explain the variation in epidemic patterns and overall mortality observed. We show that city-specific per-capita excess mortality in 1918 was significantly correlated with 1917 per-capita mortality, indicating some intrinsic variation in overall mortality, perhaps related to sociodemographic factors. In the subset of 23 cities for which we had partial data on the timing of interventions, an even stronger correlation was found between excess mortality and how early in the epidemic interventions were introduced. We then fitted an epidemic model to weekly mortality in 16 cities with nearly complete intervention-timing data and estimated the impact of interventions. The model reproduced the observed epidemic patterns well. In line with theoretical arguments, we found the time-limited interventions used reduced total mortality only moderately (perhaps 10–30%), and that the impact was often very limited because of interventions being introduced too late and lifted too early. San Francisco, St. Louis, Milwaukee, and Kansas City had the most effective interventions, reducing transmission rates by up to 30–50%. Our analysis also suggests that individuals reactively reduced their contact rates in response to high levels of mortality during the pandemic.
661 citations
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Harvard University1, University of Otago2, Universidad Autónoma Metropolitana3, Stony Brook University4, Katholieke Universiteit Leuven5, Utrecht University6, University College Hospital, Ibadan7, Peking University8, St George's Hospital9, University of Tokyo10, University of Paris11, Mental Health Services12, Pontifical Xavierian University13, All India Institute of Medical Sciences14, New Bulgarian University15, University of São Paulo16
TL;DR: Using data from over 100,000 individuals in 21 countries participating in the WHO World Mental Health Surveys, Matthew Nock and colleagues investigate which mental health disorders increase the odds of experiencing suicidal thoughts and actual suicide attempts.
Abstract: Background: Suicide is a leading cause of death worldwide. Mental disorders are among the strongest predictors of suicide; however, little is known about which disorders are uniquely predictive of suicidal behavior, the extent to which disorders predict suicide attempts beyond their association with suicidal thoughts, and whether these associations are similar across developed and developing countries. This study was designed to test each of these questions with a focus on nonfatal suicide attempts. Methods and Findings: Data on the lifetime presence and age-of-onset of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) mental disorders and nonfatal suicidal behaviors were collected via structured face-to-face interviews with 108,664 respondents from 21 countries participating in the WHO World Mental Health Surveys. The results show that each lifetime disorder examined significantly predicts the subsequent first onset of suicide attempt (odds ratios [ORs] = 2.9–8.9). After controlling for comorbidity, these associations decreased substantially (ORs = 1.5–5.6) but remained significant in most cases. Overall, mental disorders were equally predictive in developed and developing countries, with a key difference being that the strongest predictors of suicide attempts in developed countries were mood disorders, whereas in developing countries impulse-control, substance use, and post-traumatic stress disorders were most predictive. Disaggregation of the associations between mental disorders and nonfatal suicide attempts showed that these associations are largely due to disorders predicting the onset of suicidal thoughts rather than predicting progression from thoughts to attempts. In the few instances where mental disorders predicted the transition from suicidal thoughts to attempts, the significant disorders are characterized by anxiety and poor impulse-control. The limitations of this study include the use of retrospective self-reports of lifetime occurrence and age-of-onset of mental disorders and suicidal behaviors, as well as the narrow focus on mental disorders as predictors of nonfatal suicidal behaviors, each of which must be addressed in future studies. Conclusions: This study found that a wide range of mental disorders increased the odds of experiencing suicide ideation. However, after controlling for psychiatric comorbidity, only disorders characterized by anxiety and poor impulse-control predict which people with suicide ideation act on such thoughts. These findings provide a more fine-grained understanding of the associations between mental disorders and subsequent suicidal behavior than previously available and indicate that mental disorders predict suicidal behaviors similarly in both developed and developing countries. Future research is needed to delineate the mechanisms through which people come to think about suicide and subsequently progress from ideation to attempts.
661 citations
Authors
Showing all 58756 results
Name | H-index | Papers | Citations |
---|---|---|---|
Ronald C. Kessler | 274 | 1332 | 328983 |
Albert Hofman | 267 | 2530 | 321405 |
Douglas G. Altman | 253 | 1001 | 680344 |
Hans Clevers | 199 | 793 | 169673 |
Craig B. Thompson | 195 | 557 | 173172 |
Patrick W. Serruys | 186 | 2427 | 173210 |
Ruedi Aebersold | 182 | 879 | 141881 |
Dennis S. Charney | 179 | 802 | 122408 |
Kenneth S. Kendler | 177 | 1327 | 142251 |
Jean Louis Vincent | 161 | 1667 | 163721 |
Vilmundur Gudnason | 159 | 837 | 123802 |
Monique M.B. Breteler | 159 | 546 | 93762 |
Lex M. Bouter | 158 | 767 | 103034 |
Elio Riboli | 158 | 1136 | 110499 |
Roy F. Baumeister | 157 | 650 | 132987 |