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101.
Because of their surface localization, G protein-coupled receptors (GPCRs) are often pharmaceutical targets as they respond to a variety of extracellular stimuli (e.g., light, hormones, small molecules) that may activate or inhibit a downstream signaling response. The adenosine A2A receptor (A2AR) is a well-characterized GPCR that is expressed widely throughout the human body, with over 10 crystal structures determined. Truncation of the A2AR C-terminus is necessary for crystallization as this portion of the receptor is long and unstructured; however, previous work suggests shortening of the A2AR C-terminus from 412 to 316 amino acids (A2AΔ316R) ablates downstream signaling, as measured by cAMP production, to below that of constitutive full-length A2AR levels. As cAMP production is downstream of the first activation event—coupling of G protein to its receptor—investigating that first step in activation is important in understanding how the truncation effects native GPCR function. Here, using purified receptor and Gαs proteins, we characterize the association of A2AR and A2AΔ316R to Gαs with and without GDP or GTPγs using surface plasmon resonance (SPR). Gαs affinity for A2AR was greatest for apo-Gαs, moderately affected in the presence of GDP and nearly completely ablated by the addition of GTPγs. Truncation of the A2AR C-terminus (A2AΔ316R) decreased the affinity of the unliganded receptor for Gαs by ~20%, suggesting small changes to binding can greatly impact downstream signaling.  相似文献   
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Wildlife models focused solely on a single strong influence (e.g., habitat components, wildlife harvest) are limited in their ability to detect key mechanisms influencing population change. Instead, we propose integrated modeling in the context of cumulative effects assessment using multispecies population dynamics models linked to landscape-climate simulation at large spatial and temporal scales. We developed an integrated landscape and population simulation model using ALCES Online as the model-building platform, and the model accounted for key ecological components and relationships among moose (Alces alces), grey wolves (Canis lupus nubilus), and woodland caribou (Rangifer tarandus caribou) in northern Ontario, Canada. We simulated multiple scenarios over 5 decades (beginning 2020) to explore sensitivity to climate change and land use and assessed effects at multiple scales. The magnitude of effect and the relative importance of key factors (climate change, roads, and habitat) differed depending on the scale of assessment. Across the full extent of the study area (654,311km2 [ecozonal scale]), the caribou population declined by 26% largely because of climate change and associated predator-prey response, which led to caribou range recession in the southern part of the study area. At the caribou range scale (108,378 km2), which focused on 2 herds in the northern part of the study area, climate change led to a 10% decline in the population and development led to an additional 7% decline. At the project scale (8,331 km2), which was focused more narrowly on the landscape surrounding 4 proposed mines, the caribou population declined by 29% largely in response to simulated development. Given that observed caribou population dynamics were sensitive to the cumulative effects of climate change, land use, interspecific interactions, and scale, insights from the analysis might not emerge under a less complex model. Our integrated modeling framework provides valuable support for broader regional assessments, including estimation of risk to caribou and Indigenous food security, and for developing and evaluating potential caribou recovery strategies. © 2021 The Authors. The Journal of Wildlife Management published by Wiley Periodicals LLC on behalf of The Wildlife Society.  相似文献   
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A multilayer network approach combines different network layers,which are connected by interlayer edges,to create a single mathematical object.These networks can contain a variety of information types and represent different aspects of a system.However,the process for selecting which information to include is not always straightforward.Using data on 2 agonistic behaviors in a captive population of monk parakeets(Myiopsitta monachus),we developed a framework for investigating how pooling or splitting behaviors at the scale of dyadic relationships(between 2 individuals)affects individual-and group-level social properties.We designed 2 reference models to test whether randomizing the number of interactions across behavior types results in similar structural patterns as the observed data.Although the behaviors were correlated,the first reference model suggests that the 2 behaviors convey different information about some social properties and should therefore not be pooled.However,once we controlled for data sparsity,we found that the observed measures corresponded with those from the second reference model.Hence,our initial result may have been due to the unequal frequencies of each behavior.Overall,our findings support pooling the 2 behaviors.Awareness of how selected measurements can be affected by data properties is warranted,but nonetheless our framework disentangles these efforts and as a result can be used for myriad types of behaviors and questions.This framework will help researchers make informed and data-driven decisions about which behaviors to pool or separate,prior to using the data in subsequent multilayer network analyses.  相似文献   
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Pine barrens are open‐canopy ecological communities once prevalent on sandy soils across the northern Great Lakes Region of the United States and Canada, though fire suppression and plantation forestry have now reduced them to a few isolated areas. Efforts to restore pine barrens are underway on some public lands, but lack of knowledge on the social and ecological issues and challenges that affect these projects impedes fuller progress. As a precursor to designing a public preference survey for pine barrens restoration, we sought input from those with expert knowledge about pine barrens. Using a three‐round modified Delphi survey, forest land managers and researchers identified the key characteristics of pine barrens and important current and future management challenges. Key characteristics were related to fire, landscape structure, plant and animal species, soils, and social themes. Current and future challenges were related to landscape, invasive species, social, economic, climate change, and science themes. Four social issues (education, fire acceptance, fire risk, aesthetics) were rated among the top current challenges but none of them maintained prominence as future challenges. Potential explanations for this shift are that the experts felt these social concerns would be resolved in time or that other issues, such as development pressures and budgets for carrying out restoration, would become greater future challenges. Our approach can be used by managers and researchers to better understand the ecosystems they seek to restore and to communicate with public stakeholders about restoration efforts.  相似文献   
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The enantiopure (1 S, 2 S )- cis -dihydrodiol metabolites 2B - 5B have been obtained in low yield from the corresponding monosubstituted halobenzene substrates 2A - 5A, using a wild-type strain of Pseudomonas putida (ML2) containing benzene dioxygenase (BDO). Benzene cis -dihydrodiol dehydrogenase (BCD) from P. putida ML2 and naphthalene cis -dihydrodiol dehydrogenase (NCD) from P. putida 8859 were purified and used in a comparative study of the stereoselective biotransformation of cis -dihydrodiol enantiomers 2B - 5B. The BCD and NCD enzymes were found to accept cis -dihydrodiol enantiomers of monosubstituted benzene cis -dihydrodiol substrates 2B - 5B of opposite absolute configuration. The acyclic alkene 1,2-diols 10 - 17 were also found to be acceptable substrates for BCD.  相似文献   
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The relations between fathers' and mothers' home literacy involvement at 24 months and children's cognitive and social emotional development in preschool were examined using a large sample of African American and Caucasian families (N = 5190) from the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B). Hierarchical regression analyses revealed that both fathers' and mothers' home literacy involvement positively contributed to children's cognitive and social emotional development. Specifically, fathers and mothers who participated in more frequent home literacy involvement (e.g., shared book reading) had children with better reading, math, and social emotional outcomes (i.e., sustained attention and fewer negative behaviors) in preschool. Findings suggest that increasing family literacy involvement can have positive benefits for children's cognitive and social emotional skills during the developmentally important early childhood years.  相似文献   
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Bit and bridle accessories improperly fitted in ridden horses can cause oral trauma such as bone spurs, commissure ulceration, and tongue lacerations. This study was used to identify, grade, and compare the types of oral traumas commonly found within polo ponies and race horses. Injuries were assessed visually and by palpation on the tongue, lips’ commissures, and interdental space. A total of 50 polo ponies and 50 race horses were sampled in the South of England. A Poisson model was successfully fitted to the data (p < .001), and the variables of discipline (p < .001), injury type (p < .001), and age (p < .001) were significant. Race horses with snaffle bits were predisposed to significantly higher severities and prevalence of oral trauma than were polo ponies in gag bits. Only polo ponies were observed with tongue trauma. Race horses had higher severities of injuries in the commissures and bone spurs. Positive correlations were found between age and/or time in sport and induced biting injuries. Polo ponies had been playing longer before the occurrence of injuries.  相似文献   
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