KPC1 alleviates hypoxia/reoxygenation-induced apoptosis in rat cardiomyocyte cells though BAX degradation

Bax triggers cell apoptosis by permeabilizing the outer mitochondrial membrane, leading to membrane potential loss and cytochrome c release. However, it is unclear if proteasomal degradation of Bax is involved in the apoptotic process, especially in heart ischemia-reperfusion (I/R)-induced injury. In the present study, KPC1 expression was heightened in left ventricular cardiomyocytes of patients with coronary heart disease (CHD), in I/R-myocardium in vivo and in hypoxia and reoxygenation (H/R)-induced cardiomyocytes in vitro. Overexpression of KPC1 reduced infarction size and cell apoptosis in I/R rat hearts. Similarly, the forced expression of KPC1 restored mitochondrial membrane potential (MMP) and cytochrome c release driven by H/R in H9c2 cells, whereas reducing cell apoptosis, and knockdown of KPC1 by short-hairpin RNA (shRNA) deteriorated cell apoptosis induced by H/R. Mechanistically, forced expression of KPC1 promoted Bax protein degradation, which was abolished by proteasome inhibitor MG132, suggesting that KPC1 promoted proteasomal degradation of Bax. Furthermore, KPC1 prevented basal and apoptotic stress-induced Bax translocation to mitochondria. Bax can be a novel target for the antiapoptotic effects of KPC1 on I/R-induced cardiomyocyte apoptosis and render mechanistic penetration into at least a subset of the mitochondrial effects of KPC1.     

β3-adrenergic receptor activation plays an important role in the depressed myocardial contractility via both elevated levels of cellular free Zn2+ and reactive nitrogen species

Role of β₃-AR dysregulation, as either cardio-conserving or cardio-disrupting mediator, remains unknown yet. Therefore, we examined the molecular mechanism of β₃-AR activation in depressed myocardial contractility using a specific agonist CL316243 or using β₃-AR overexpressed cardiomyocytes. Since it has been previously shown a possible correlation between increased cellular free Zn²⁺ ([Zn²⁺]_i) and depressed cardiac contractility, we first demonstrated a relation between β₃-AR activation and increased [Zn²⁺]_i, parallel to the significant depolarization in mitochondrial membrane potential in rat ventricular cardiomyocytes. Furthermore, the increased [Zn²⁺]_i induced a significant increase in messenger RNA (mRNA) level of β₃-AR in cardiomyocytes. Either β₃-AR activation or its overexpression could increase cellular reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels, in line with significant changes in nitric oxide (NO)-pathway, including increases in the ratios of pNOS3/NOS3 and pGSK-3β/GSK-3β, and PKG expression level in cardiomyocytes. Although β₃-AR activation induced depression in both Na⁺- and Ca²⁺-currents, the prolonged action potential (AP) seems to be associated with a marked depression in K⁺-currents. The β₃-AR activation caused a negative inotropic effect on the mechanical activity of the heart, through affecting the cellular Ca²⁺-handling, including its effect on Ca²⁺-leakage from sarcoplasmic reticulum (SR). Our cellular level data with β₃-AR agonism were supported with the data on high [Zn²⁺]_i and β₃-AR protein-level in metabolic syndrome (MetS)-rat heart. Overall, our present data can emphasize the important deleterious effect of β₃-AR activation in cardiac remodeling under pathological condition, at least, through a cross-link between β₃-AR activation, NO-signaling, and [Zn²⁺]_i pathways. Moreover, it is interesting to note that the recovery in ER-stress markers with β₃-AR agonism in hyperglycemic cardiomyocytes is favored. Therefore, how long and to which level the β₃-AR agonism would be friend or become foe remains to be mystery, yet.     

Using spotlight observations to predict resource selection and abundance for white-tailed deer

Spotlight surveys for white-tailed deer (Odocoileus virginianus) can yield large presence-only datasets applicable to a variety of resource selection modeling procedures. By understanding how populations distribute according to a given resource for a reference area, density and abundance can be predicted across new areas assuming the relationship between habitat quality (measured by an index of selection) and species distribution are equivalent. Habitat-based density estimators have been applied to wildlife species and are useful for addressing conservation and management concerns. Although achieving reliable population estimates is a primary goal for spotlighting studies, presence-only models have yet to be applied to spotlight data for estimating habitat selection and abundance for deer. From 2012 to 2017, we conducted spring spotlight surveys in each of 99 counties in Iowa, USA, and collected spatial locations for 20,149 groups of deer (n = 71,323 individuals). We used a resource selection function (RSF) based on deer locations to predict the relative probability of use for deer at the population level and to estimate statewide abundance. The number of deer observed statewide increased significantly with increasing RSF value for all years and the mean RSF value along survey transects explained 59% of the variability in county-level deer counts, indicating that a functional response between habitat quality and deer distribution existed at landscape scales. We applied our RSF to a habitat-based density estimator (extrapolation) and zero-inflated Poisson (ZIP) and negative binomial (ZINB) count models to predict statewide abundance from spotlight counts. Population estimates for 2012 were variable, indicating that atypical weather conditions may affect spotlight counts and population estimates in some years. For 2013–2017, we predicted a mean population of 439,129 (95% CI ∼ ± 55,926), 440,360 (∼ ± 43,676), and 465,959 (∼ ± 51,242) deer across years for extrapolation, ZIP, and ZINB models, respectively. Estimates from all models were not significantly different than estimates from an existing deer population accounting model in Iowa for 2013 and 2016, and differed by <76,000 deer for all models from 2013–2017. Extrapolation and ZIP models performed similarly and differed by <2,897 deer across all years, whereas ZINB models showed inconsistencies in model convergence and precision of estimates. Our results indicate that presence-only models are capable of producing reliable and precise estimates of resource selection and abundance for deer at broad landscape scales in Iowa and provide a tool for estimating deer abundance in a spatially explicit manner. © 2019 The Wildlife Society.     

A century of conservation: The ongoing recovery of Svalbard reindeer

Several caribou and reindeer (Rangifer tarandus) populations have experienced recent population declines, often attributed to anthropogenic stressors such as harvesting, landscape fragmentation, and climate change. Svalbard reindeer (R. t. platyrhynchus), the wild reindeer subspecies endemic to the high-Arctic Svalbard archipelago, was protected in 1925, after most subpopulations had been eradicated by harvest. Although direct pressure from harvest has ceased, indirect anthropogenic stressors from environmental changes have increased in this climate change hot spot. An assessment of the current distribution and abundance is therefore urgently needed. We combined distance sampling (300 km transects, n = 489 reindeer groups) and total counts (1,350 km², n = 1,349 groups) to estimate the Svalbard reindeer distribution and abundance across its entire range, which we compared with historical data from the literature and radiocarbon-dated bones. Reindeer have now recolonized nearly all non-glaciated land (i.e., areas occupied prior to human presence), and their spatial variation in abundance reflects vegetation productivity. Independent of vegetation productivity, however, recently recolonized areas have lower reindeer densities than areas not subject to past extirpation. This suggests that recovery from past overharvesting is still in progress. These incompletely recovered areas are potential targets for increased monitoring frequency and maintaining strict conservation to follow the Svalbard management goal (i.e., virtually untouched wilderness areas). Because of such ongoing recolonization, possibly combined with vegetation greening effects of recent warming, our status estimate of Svalbard reindeer abundance (22,435 [95% CI = 21,452–23,425]) is more than twice a previous estimate based on opportunistic counts. Thus, although our study demonstrates the successful outcome of strict harvesting control implemented a century ago, current and future population trajectories are likely shaped by climate change. © 2019 The Authors. Journal of Wildlife Management Published by Wiley Periodicals, Inc. on behalf of The Wildlife Society.     

Factors associated with black bear density and implications for management

Wildlife density estimates are important to accurately formulate population management objectives and understand the relationship between habitat characteristics and a species’ abundance. Despite advances in density and abundance estimation methods, management of common game species continues to be challenged by a lack of reliable population estimates. In Washington, USA, statewide American black bear (Ursus americanus) abundance estimates are predicated on density estimates derived from research in the 1970s and are hypothesized to be a function of precipitation and vegetation, with higher densities in western Washington. To evaluate current black bear density and landscape relationships in Washington, we conducted a 4-year capture-recapture study in 2 areas of the North Cascade Mountains using 2 detection methods, non-invasive DNA collection and physical capture and deployment of global positioning system (GPS) collars. We integrated GPS telemetry from collared bears with spatial capture-recapture (SCR) data and created a SCR-resource selection model to estimate density as a function of spatial covariates and test the hypothesis that density is higher in areas with greater vegetative food resources. We captured and collared 118 bears 132 times and collected 7,863 hair samples at hair traps where we identified 537 bears from 1,237 detections via DNA. The most-supported model in the western North Cascades depicted a negative relationship between black bear density and an index of human development. We estimated bear density at 20.1 bears/100 km², but density varied from 13.5/100 km² to 27.8 bears/100 km² depending on degree of human development. The model best supported by the data in the eastern North Cascades estimated an average density of 19.2 bears/100 km², which was positively correlated with primary productivity, with resulting density estimates ranging from 7.1/100 km² to 33.6 bears/100 km². The hypothesis that greater precipitation and associated vegetative production in western Washington supports greater bear density compared to eastern Washington was not supported by our data. In western Washington, empirically derived average density estimates (including cubs) were nearly 50% lower than managers expected prior to our research. In eastern Washington average black bear density was predominantly as expected, but localized areas of high primary productivity supported greater than anticipated bear densities. Our findings underscore the importance that black bear density is not likely uniform and management risk may be increased if an average density is applied at too large a scale. Disparities between expected and empirically derived bear density illustrate the need for more rigorous monitoring to understand processes that affect population numbers throughout the jurisdiction, and suggest that management plans may need to be reevaluated to determine if current harvest strategies are achieving population objectives. © 2019 The Wildlife Society.     

微生物组学研究的“淘金时代”

人体及动物肠道中生存着数量庞大的共生微生物;这些微生物无时无刻不参与着宿主的生命活动。揭示这些共生微生物在宿主体内的变化规律、与宿主之间的依存和博弈关系等,将使人类更加全面的认知高等生物体的生命本质。本专刊从肠道微生物与疾病、肠道微生物群落结构、肠道微生物与宿主互作、肠道微生物资源和肠道微生物研究方法 5个层面展示了我国科研工作者在肠道微生物研究领域的新进展及新观点。     

BAmSA: Visualising transmembrane regions in protein complexes using biotinylated amphipols and electron microscopy

Membrane protein (MP) complexes play key roles in all living cells. Their structural characterisation is hampered by difficulties in purifying and crystallising them. Recent progress in electron microscopy (EM) have revolutionised the field, not only by providing higher-resolution structures for previously characterised MPs but also by yielding first glimpses into the structure of larger and more challenging complexes, such as bacterial secretion systems. However, the resolution of pioneering EM structures may be difficult and their interpretation requires clues regarding the overall organisation of the complexes. In this context, we present BAmSA, a new method for localising transmembrane (TM) regions in MP complexes, using a general procedure that allows tagging them without resorting to neither genetic nor chemical modification. Labels bound to TM regions can be visualised directly on raw negative-stain EM images, on class averages, or on three-dimensional reconstructions, providing a novel strategy to explore the organisation of MP complexes.     

Accounting for phenology in the analysis of animal movement

The analysis of animal tracking data provides important scientific understanding and discovery in ecology. Observations of animal trajectories using telemetry devices provide researchers with information about the way animals interact with their environment and each other. For many species, specific geographical features in the landscape can have a strong effect on behavior. Such features may correspond to a single point (eg, dens or kill sites), or to higher dimensional subspaces (eg, rivers or lakes). Features may be relatively static in time (eg, coastlines or home‐range centers), or may be dynamic (eg, sea ice extent or areas of high‐quality forage for herbivores). We introduce a novel model for animal movement that incorporates active selection for dynamic features in a landscape. Our approach is motivated by the study of polar bear (Ursus maritimus) movement. During the sea ice melt season, polar bears spend much of their time on sea ice above shallow, biologically productive water where they hunt seals. The changing distribution and characteristics of sea ice throughout the year mean that the location of valuable habitat is constantly shifting. We develop a model for the movement of polar bears that accounts for the effect of this important landscape feature. We introduce a two‐stage procedure for approximate Bayesian inference that allows us to analyze over 300 000 observed locations of 186 polar bears from 2012 to 2016. We use our model to estimate a spatial boundary of interest to wildlife managers that separates two subpopulations of polar bears from the Beaufort and Chukchi seas.     

The pearl necklace model in protein A chromatography: Molecular mechanisms at the resin interface

Staphylococcal protein A chromatography is an established core technology for monoclonal antibody purification and capture in the downstream processing. MabSelect SuRe involves a tetrameric chain of a recombinant form of the B domain of staphylococcal protein A, called the Z-domain. Little is known about the stoichiometry, binding orientation, or preferred binding. We analyzed small-angle X-ray scattering data of the antibody–protein A complex immobilized in an industrial highly relevant chromatographic resin at different antibody concentrations. From scattering data, we computed the normalized radial density distributions. We designed three-dimensional (3D) models with protein data bank crystallographic structures of an IgG1 (the isoform of trastuzumab, used here; Protein Data Bank: 1HZH) and the staphylococcal protein A B domain (the native form of the recombinant structure contained in MabSelect SuRe resin; Protein Data Bank: 1BDD). We computed different binding conformations for different antibody to protein A stoichiometries (1:1, 2:1, and 3:1) and compared the normalized radial density distributions computed from 3D models with those obtained from the experimental data. In the linear range of the isotherm we favor a 1:1 ratio, with the antibody binding to the outer domains in the protein A chain at very low and high concentrations. In the saturation region, a 2:1 ratio is more likely to occur. A 3:1 stoichiometry is excluded because of steric effects.