The neuregulin 4 gene encodes at least five different variants (designated A1, A2, B1, B2 and B3) produced as a result of alternative splicing. We have determined their sites of expression in normal ...human adult tissues using isoform-specific antibodies. Their expression is cell type specific and differs in subcellular location suggesting that they may have varied functions in these contexts. We have shown in a panel of prostate cancers that each form is present to differing degrees, and that principal component analysis indicates that there are three patterns of expression. Some isoforms were positively correlated with high prostate-specific antigen levels and others were inversely associated with Gleason score. Synthetic, refolded A forms promoted lamellipodia and filopodia formation in cells expressing the ErbB4 (CTa) receptor and stimulated cell motility in wound healing assays. The data suggest that the different forms have varied sites of expression and function, and this includes effects on cell architecture and motility.
The neuregulin (NRG) 1, 2, and 3 genes undergo extensive alternative mRNA splicing, which results in variants that show structural and functional diversity. The aims of this study were to establish ...whether the fourth member of this family, NRG4, is expressed in prostate cancer, if it is alternatively spliced and whether any functional differences between the variants could be observed.
The expression of NRG4 was determined using immunohistochemical staining of 40 cases of primary prostate cancer. Bioinformatic analysis and reverse transcription-PCR (RT-PCR) using NRG4 isotype-specific primers on a panel of normal and prostate cancer cell lines were used to identify alternatively spliced NRG4 variants. Expression of these variants was determined using isotype-specific antibodies. Transfection into Cos-7 cells of two of these green fluorescent protein-tagged variants allowed analysis of their subcellular location. Four of the variants were chemically synthesized and tested for their ability to activate the ErbB4 receptor.
NRG4 was variably expressed in the cytoplasm in the majority of prostate cancer cases, and in a subset of cases in the membrane, high levels were associated with advanced disease stage. Four novel NRG4 splice variants (NRGA2, NRG4 B1-3) were characterized, where each seemed to have a different subcellular location and were also expressed in the cytoplasm of the prostate tumors. NRG4 B3 was also present in endothelial cells. In transfected cells, the A type variant (NRG4 A1) was localized to the membrane, whereas the B type variant (NRG4 B1), which lacks the predicted transmembrane region, had an intracellular localization. Only the variants with an intact epidermal growth factor-like domain activated ErbB4 signaling.
NRG4 overexpression is associated with advanced-stage prostate cancer. The alternative splice variants may have different roles in cell signaling, some acting as classic receptor ligands and some with as-yet unknown functions.
Climate warming is driving changes in species distributions and community composition. Many species have a so‐called climatic debt, that is, shifts in range lag behind shifts in temperature ...isoclines. Inside protected areas (PAs), community changes in response to climate warming can be facilitated by greater colonization rates by warm‐dwelling species, but also mitigated by lowering extirpation rates of cold‐dwelling species. An evaluation of the relative importance of colonization‐extirpation processes is important to inform conservation strategies that aim for both climate debt reduction and species conservation. We assessed the colonization‐extirpation dynamics involved in community changes in response to climate inside and outside PAs. To do so, we used 25 years of occurrence data of nonbreeding waterbirds in the western Palearctic (97 species, 7071 sites, 39 countries, 1993–2017). We used a community temperature index (CTI) framework based on species thermal affinities to investigate species turnover induced by temperature increase. We determined whether thermal community adjustment was associated with colonization by warm‐dwelling species or extirpation of cold‐dwelling species by modeling change in standard deviation of the CTI (CTISD). Using linear mixed‐effects models, we investigated whether communities in PAs had lower climatic debt and different patterns of community change than communities outside PAs. For CTI and CTISD combined, communities inside PAs had more species, higher colonization, lower extirpation, and lower climatic debt (16%) than communities outside PAs. Thus, our results suggest that PAs facilitate 2 independent processes that shape community dynamics and maintain biodiversity. The community adjustment was, however, not sufficiently fast to keep pace with the large temperature increases in the central and northeastern western Palearctic. Our results underline the potential of combining CTI and CTISD metrics to improve understanding of the colonization‐extirpation patterns driven by climate warming.
Beneficios de las Áreas Protegidas para las Aves Acuáticas No Reproductoras que Están Ajustando su Distribución Debido al Calentamiento Climático
Resumen
El calentamiento climático está generando cambios en la distribución y en la composición comunitaria de las especies. Muchas de ellas tienen una deuda climática, es decir, los cambios en la distribución se atrasan con respecto a los cambios en las isoclinas térmicas. Dentro de las áreas protegidas (APs), los cambios comunitarios como respuesta al calentamiento climático pueden facilitarse mediante tasas mayores de colonización por especies de climas cálidos, pero también pueden mitigarse al reducir las tasas de extirpación de las especies de climas fríos. Se requiere una evaluación de la importancia relativa de los procesos de colonización‐extirpación para orientar las estrategias de conservación que buscan la reducción de la deuda climática y la conservación de las especies. Analizamos las dinámicas de colonización‐extirpación que participan en los cambios comunitarios como respuesta al clima dentro y fuera de las APs. Para realizar lo anterior, usamos datos tomados durante 25 años de la presencia de aves acuáticas no reproductoras en el Paleártico occidental (97 especies, 7,071 sitios, 39 países, 1993–2017). Usamos un marco de trabajo del índice de temperatura comunitaria (ITC) basado en las afinidades térmicas de las especies para así investigar la rotación de especies inducida por el incremento en la temperatura. Determinamos si el ajuste térmico en la comunidad estuvo asociado con la colonización por especies de climas cálidos o con la extirpación de especies de climas fríos al modelar el cambio mediante una desviación estándar del ITC (ITCDS). Con los modelos lineales de efectos mixtos investigamos si las comunidades dentro de las APs tenían una deuda climática más baja y patrones diferentes de cambio comunitario que las comunidades localizadas fuera de las APs. Con la combinación del ITC y deL ITCDS, las comunidades dentro de las APs tuvieron más especies, una mayor colonización, una menor extirpación y una deuda climática más baja (16%) que las comunidades fuera de las APs. Por lo tanto, nuestros resultados sugieren que las APs facilitan dos procesos independientes que moldean las dinámicas comunitarias y mantienen la biodiversidad. Sin embargo, el ajuste comunitario no fue lo suficientemente rápido para mantener el paso de los grandes incrementos en la temperatura de las regiones central y noreste del Paleártico occidental. Nuestros resultados resaltan el potencial que tiene la combinación de las medidas del ITC y del ICTDS para mejorar el entendimiento de los patrones de colonización‐extirpación causados por el calentamiento climático.
【摘要】
气候变暖正在引起物种分布和群落组成的变化。许多物种都背负着所谓的 “气候债务”, 即分布范围的变化滞后于温度的变化。气候变暖背景下, 保护地中适应温暖环境的物种较高的定殖率可以促进群落变化, 适应寒冷环境的物种灭绝率下降也可以减缓影响。评估定殖–灭绝过程的相对重要性, 对于制定旨在减少气候债和促进物种保护的保护战略而言十分重要。本研究利用西古北界非繁殖水鸟 25 年的出现记录 (97 个物种, 7071 个位点, 39 个国家, 1993–2017 年) , 评估了保护地内外鸟类群落响应气候变化过程中的定殖–灭绝动态。我们使用基于物种对温度亲和性的群落温度指数框架探究了温度升高引起的物种更替。通过模拟群落温度指数标准偏差的变化, 我们确定了群落对温度的调整是否与适应温暖环境的物种的定殖或适应寒冷环境的物种的灭绝有关。接下来, 我们利用线性混合效应模型分析了保护地内与保护地外的群落相比是否具有较低的气候债务和不同的群落变化格局。结合群落温度指数与其标准偏差, 我们发现保护地内的群落比保护地外的具有更多的物种、更高的定殖率、更低的灭绝率和更低的气候债务 (16%) 。因此, 我们的结果表明, 保护地促进了群落动态形成和生物多样性维持这两个独立过程。然而, 群落调整的速度不足以跟上古北界中部和东北部地区气温的大幅上升。我们的结果强调了群落温度指数和群落温度指数标准偏差这两个指标相结合, 有潜力提高对气候变暖导致的定殖–灭绝格局的理解。【翻译: 胡怡思; 审校: 聂永刚】
Article impact statement: Protected areas are needed to facilitate waterbird distribution change in response to climate warming in the western Palearctic.
Migratory waterbirds require an effectively conserved cohesive network of wetland areas throughout their range and life-cycle. Under rapid climate change, protected area (PA) networks need to be able ...to accommodate climate-driven range shifts in wildlife if they are to continue to be effective in the future. Thus, we investigated geographical variation in the relationship between local temperature anomaly and the abundance of 61 waterbird species during the wintering season across Europe and North Africa during 1990–2015. We also compared the spatio-temporal effects on abundance of sites designated as PAs, Important Bird and Biodiversity Areas (IBAs), both, or neither designation (Unlisted). Waterbird abundance was positively correlated with temperature anomaly, with this pattern being strongest towards north and east Europe. Waterbird abundance was higher inside IBAs, whether they were legally protected or not. Trends in waterbird abundance were also consistently more positive inside both protected and unprotected IBAs across the whole study region, and were positive in Unlisted wetlands in southwestern Europe and North Africa. These results suggest that IBAs are important sites for wintering waterbirds, but also that populations are shifting to unprotected wetlands (some of which are IBAs). Such IBAs may therefore represent robust candidate sites to expand the network of legally protected wetlands under climate change in north-eastern Europe. These results underscore the need for monitoring to understand how the effectiveness of site networks is changing under climate change.
Aim
Many species are showing distribution shifts in response to environmental change. We explored (a) the effects of inter‐annual variation in winter weather conditions on non‐breeding distributional ...abundance of waterbirds exploiting different habitats (deep‐water, shallow water, farmland) and (b) the long‐term shift in the population centroid of these species and investigate its link to changes in weather conditions.
Location
Europe.
Methods
We fitted generalized additive mixed Models to a large‐scale, 24‐year dataset (1990–2013) describing the winter distributional abundance of 25 waterbird species. We calculated the annual and long‐term (3‐year periods) population centroid of each species and used the winter North Atlantic Oscillation (NAO) index to explain the inter‐annual and long‐term shifts in their location.
Results
(a) Year‐to‐year southwestwards shifts in the population centroids of deep‐ and shallow‐water species were linked to negative NAO values. Shallow‐water species shifted northeastwards associated with positive NAO values and the distance shifted increased with increasing NAO. Deep‐water species shifted northeastwards up to zero NAO indices, but showed no further increase at higher NAO values. (b) Deep‐water species showed long‐term northeastwards shifts in distributional abundance throughout the 1990s and the 2000s. Shallow‐water species, on the other hand, shifted northeastwards during the 1990s and early 2000s, but southwestwards thereafter. There were no significant links between the NAO and year‐to‐year movements or long‐term shifts in farmland species’ population centroid.
Main Conclusions
We provide evidence for a link between both year‐to‐year and long‐term changes in waterbird winter distributional abundances at large geographical scales to short‐ and long‐term changes in winter weather conditions. We also show that species using shallow water, deep‐water and farmland habitats responded differently, especially at high NAO values. As well as important ecological implications, these findings contribute to the development of future conservation measures for these species under current and future climate change.
Protected area networks help species respond to climate warming. However, the contribution of a site's environmental and conservation‐relevant characteristics to these responses is not well ...understood. We investigated how composition of nonbreeding waterbird communities (97 species) in the European Union Natura 2000 (N2K) network (3018 sites) changed in response to increases in temperature over 25 years in 26 European countries. We measured community reshuffling based on abundance time series collected under the International Waterbird Census relative to N2K sites’ conservation targets, funding, designation period, and management plan status. Waterbird community composition in sites explicitly designated to protect them and with management plans changed more quickly in response to climate warming than in other N2K sites. Temporal community changes were not affected by the designation period despite greater exposure to temperature increase inside late‐designated N2K sites. Sites funded under the LIFE program had lower climate‐driven community changes than sites that did not received LIFE funding. Our findings imply that efficient conservation policy that helps waterbird communities respond to climate warming is associated with sites specifically managed for waterbirds.
Resumen
Las redes de áreas protegidas ayudan a las especies a responder al calentamiento climático. Sin embargo, se sabe muy poco sobre la contribución de las características ambientales y relevantes para la conservación de un sitio a estas respuestas. Investigamos cómo la composición de las comunidades no reproductivas de aves acuáticas (97 especies) en la red (3,018 sitios) Natura 2000 de la Unión Europea (N2K) cambió en respuesta a los incrementos de la temperatura durante más de 25 años en 26 países europeos. Medimos la reorganización comunitaria con base en series temporales de abundancia recolectadas durante el Censo Internacional de Aves Acuáticas en relación con los objetivos de conservación de los sitios N2K, el periodo de asignación de fondos y el estado del plan de manejo. La composición comunitaria de las aves acuáticas en los sitios con planes de manejo y designados explícitamente para su protección cambió más rápidamente en respuesta al calentamiento climático que en otros sitios N2K. Los cambios comunitarios temporales no se vieron afectados por el periodo de asignación a pesar de una mayor exposición al incremento de la temperatura dentro de los sitios N2K de asignación tardía. Los sitios financiados por el programa LIFE tuvieron menos cambios comunitarios causados por el clima que los sitios que no recibieron este financiamiento. Nuestros hallazgos sugieren que la política de conservación eficiente que ayuda a las comunidades de aves acuáticas a responder al calentamiento climático está asociada con sitios específicamente gestionados para las aves acuáticas.
Article impact statement: Protected area management and species targets help waterbird communities respond to climate warming inside the Natura 2000 network.
British wetlands are used by many different resident and migratory wildfowl species for some or all of the winter months. The Wetland Bird Survey (WeBS) is a scheme set up with the objectives of ...assessing the size of waterbird populations, determining trends in numbers and distribution and assessing the importance of individual sites for waterbirds as part of the requirements of international conservation conventions and directives. Over three thousand sites around Britain are included in the survey, and volunteers have been undertaking counts of wildfowl species for over forty years. One of the key features of WeBS is that sites are surveyed at monthly intervals over the winter season.The analyses for the project used data for twenty-six wildfowl (sub-)species for winter seasons from 1966/67 to 2006/07. The limitations and bias of the sampling methods currently used in the Wetland Bird Survey, are examined. It is shown that post-selection of sites by the proportion of missing values, as is done currently, introduces an additional bias that impacts on reported population trends. A new site selection criteria that minimises additional bias is proposed.WeBS wildfowl data comprise monthly counts of populations that change over each winter season due to short-term immigration and emigration. Ideas and methods from the held of Functional Data Analysis are used to explore phenological changes (spatiotem-poral variation in the seasonal patterns) due to changing species distributions and to select months where the seasonal patterns are most stable.The Underhill method, of imputing missing values using a site-year-month multiplicative model and the EM algorithm to generate an annual Underhill Index, is reviewed. It is shown that the model is a poor fit to most wildfowl WeBS data sets.Currently WeBS abundance indices are calculated using the Underhill Index, which treats each species’ seasonality as stationary, using the arithmetic mean over months and sites to derive a population index. Using ideas from economics, various alternative indexing approaches to constructing a single yearly index from the monthly counts are compared with simulated examples and WeBS data.The results have implications beyond the Wetland Bird Survey, to other wildlife monitoring schemes; particularly those that monitor populations which show strong seasonal dynamics.
The endosomal sorting complexes required for transport (ESCRT) proteins mediate fundamental membrane remodeling events that require stabilizing negative membrane curvature. These include endosomal ...intralumenal vesicle formation, HIV budding, nuclear envelope closure, and cytokinetic abscission. ESCRT-III subunits perform key roles in these processes by changing conformation and polymerizing into membrane-remodeling filaments. Here, we report the 4 angstrom resolution cryogenic electron microscopy reconstruction of a one-start, double-stranded helical copolymer composed of two different human ESCRT-III subunits, charged multivesicular body protein 1B (CHMP1B) and increased sodium tolerance 1 (IST1). The inner strand comprises "open" CHMP1B subunits that interlock in an elaborate domain-swapped architecture and is encircled by an outer strand of "closed" IST1 subunits. Unlike other ESCRT-III proteins, CHMP1B and IST1 polymers form external coats on positively curved membranes in vitro and in vivo. Our analysis suggests how common ESCRT-III filament architectures could stabilize different degrees and directions of membrane curvature.
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