Allosteric Conversation in the Androgen Receptor Ligand-Binding Domain Surfaces

Androgen receptor (AR) is a major therapeutic target that plays pivotal roles in prostate cancer (PCa) and androgen insensitivity syndromes. Wepreviously proposed that compounds recruited to ligand-binding domain (LBD) surfaces could regulate AR activity in hormone-refractory PCa and discovered several surface modulators of AR function. Surprisingly, the most effective compounds bound preferentially to a surface of unknown function [binding function 3 (BF-3)] instead of the coactivator-binding site [activation function 2 (AF-2)]. Different BF-3 mutations have been identified in PCa or androgen insensitivity syndrome patients, and they can strongly affect AR activity. Further, comparison of AR x-ray structures with and without bound ligands at BF-3 and AF-2 showed structural coupling between both pockets. Here, we combine experimental evidence and molecular dynamic simulations to investigate whether BF-3 mutations affect AR LBD function and dynamics possibly via allosteric conversation between surface sites. Our data indicate that AF-2 conformation is indeed closely coupled to BF-3 and provide mechanistic proof of their structural interconnection. BF-3 mutations may function as allosteric elicitors, probably shifting the AR LBD conformational ensemble toward conformations that alter AF-2 propensity to reorganize into subpockets that accommodate N-terminal domain and coactivator peptides. The induced conformation may result in either increased or decreased AR activity. Activating BF-3 mutations also favor the formation of another pocket (BF-4) in the vicinity of AF-2 and BF-3, which we also previously identified as a hot spot for a small compound. We discuss the possibility that BF-3 may be a protein-docking site that binds to the N-terminal domain and corepressors. AR surface sites are attractive pharmacological targets to develop allosteric modulators that might be alternative lead compounds for drug design. © 2012 by The Endocrie Society

Characterization of Samples for Optimization of Infrared Stray Light Coatings

NASA’s Stratospheric Observatory for Infrared Astronomy (SOFIA) is a converted 747SP that houses a 2.5 m telescope that observes the sky through an opening in the side of the aircraft. Because it flies at altitudes up to 45,000 feet, SOFIA gets 99.99% transmission in the infrared. Multiple science instruments mount one at a time on the telescope to interpret infrared and visible light from target sources. Ball Infrared Black (BIRB) currently coats everything that the optics sees inside the telescope assembly (TA) cavity in order to eliminate noise from the glow of background sky, aircraft exhaust, and other sources. A reflectometer and emissometer were used to measure and characterize the coatings in terms of their ability to absorb stray light. These measurements were then compared to the BIRB currently used. Though Aeroglaze Z306 showed lower better (lower) reflectance values than Desothane, neither of these coatings showed better reflectance values than the current BIRB. These characterizations help us to determine an improved recipe for TA cavity coating

Short- to medium-term effects of crown and surface fires on soil respiration in a Canadian boreal forest

Fires are an important perturbation for the carbon (C) dynamics of boreal forests, especially when they are standreplacing. In North American boreal forests, crown fires are predominant and, therefore, the most studied. However, surface fires can also lead to major tree mortality with substantial implications for the C balance. Here, we assess the short- (hours to days) to medium-term (1-3 years) effects of the different fire types (surface vs. crown) on the postfire soil C effluxes in jack pine (Enos barilcsicina Lamb.) and black spruce (Picea mariana (Mill.) BSP) forest stands in the Northwest Territories, Canada. We found that while trees were instantly killed by the four crown fires studied, trees also died within 1 year after two of three surface fires studied. Associated with this tree mortality, soil autotrophic respiration decreased after both fire types, although at different timings. The soil heterotrophic respiration was either lower or unchanged when measured 1-3 years after either fire type but was increased when measured immediately after a surface fire, possibly due to the interaction between ash generation and wetting performed to suppress the fire. Our results suggest that both fire types can thus substantially alter C fluxes in the short to medium term, both through changes in vegetation and the soil environment.Peer reviewe

Seasonal resource selection of an arboreal habitat specialist in a human-dominated landscape: a case study using red panda

Human-dominated landscapes provide heterogeneous wildlife habitat. Conservation of habitat specialists, like red pandas Ailurus fulgens, inhabiting such landscapes is challenging. Therefore, information on resource use across spatial and temporal scales could enable informed-decision making with better conservation outcomes. We aimed to examine the effect of geo-physical, vegetation, and disturbance variables on fine-scale habitat selection of red pandas in one such landscape. We equipped 10 red pandas with GPS collars in eastern Nepal in 2019 and monitored them for 1 year. Our analysis was based on a generalized-linear-mixed model. We found the combined effect of geo-physical, vegetation, and disturbance variables resulted in differences in resource selection of red pandas and that the degree of response to these variables varied across seasons. Human disturbances, especially road and cattle herding activities, affected habitat utilization throughout the year whereas other variables were important only during restricted periods. For instance, geo-physical variables were influential in the premating and cub-rearing seasons while vegetation variables were important in all seasons other than premating. Red pandas selected steeper slopes with high solar insolation in the premating season while they occupied elevated areas and preferred specific aspects in the cub-rearing season. Furthermore, the utilized areas had tall bamboo in the birthing and cub-rearing seasons while they also preferred diverse tree species and high shrub cover in the latter. Our study demonstrates the significance of season-specific management, suggests the importance of specific types of vegetation during biologically crucial periods, and emphasizes the necessity to minimize disturbances throughout the year

Understanding of relationships between ground cover and rat abundances: An integrative approach for management of the oil palm agroecosystem.

Ground cover is an essential element in the selection of habitats by small mammals. It provides shelter, foraging opportunities and a hiding place from predators. In oil palm plantations rodents are abundant yet the relationships between ground cover structure and rats are not well understood. Plantation management emphasizes maximisation of oil palm yield by reducing rat damage and competition from weeds, typically through chemical control. This study examined the relationships between ground cover, including undergrowth and frond piles, and rat abundance. Rat trapping and vegetation assessment were conducted simultaneously in five study plots in the Labu Estate, Negeri Sembilan, Malaysia. Over 21,000 trap-nights 1190 individual rats were captured and these data were analysed using spatial analysis by distance indices (SADIE). No significant clustering of rats was observed within any plot over time. Redundancy analyses suggested that the overall occurrence of rats, especially Rattus argentiventer, was positively correlated with vegetation cover and height. This implies that habitat complexity is important to rats, even in a relatively simple agroecosystem. Results of the SADIE analyses were inconsistent, perhaps due to highly variable management practices in the plantations. The findings from this study suggest that using an integrated approach in the control of both weeds and rats in oil palm plantations may maximise the benefits from weeding while reducing the production loss due to rats and the need for chemical control of rats

Space use, interaction and recursion in a solitary specialized herbivore: a red panda case study

Better understanding of ecology is crucial for the success of an endangered species conservation program. There is little information available on space use, conspecific interactions and recursions by one such species, the red panda Ailurus fulgens. To address this deficiency we used GPS telemetry to examine their home range, core area, home-range overlap, dynamic interactions, and recursive movement, and investigated the effect of sex, age, and body mass on these behaviours across seasons. The median annual home range was 1.41 with nearly a quarter of this range being used as the core area. Sex and reproductive status were the key determinants of space use patterns on a seasonal scale, while body mass and age remained significant correlates for the core area. The home range of males was nearly double that of females, likely because of the polygynous mating system in red pandas. Females avoided overlapping home ranges while males overlapped home range with up to four females, and neighbouring males overlapped nearly half of their ranges. We found rare interactions between males and females outside the mating season. Red pandas showed site fidelity within their territory with seasonal variation across sex classes. We also observed high individual variation in patterns of both space use and recursion. Taken together, these results suggest that differences in biological requirements across seasons determine red panda space use patterns, conspecific interactions and recursion. But forage availability and quality, climatic factors, disturbances and habitat fragmentation are also likely to influence these behaviours, and these need to be investigated

Powers, inequalities and vulnerabilities

This research addresses the gap that is present in both missiology and family and youth ministry. Missiology does not focus on children and youth specifically, while this is the largest population in the developing world. On the other hand, family and youth ministry has a more pastoral than missional approach, not always taking cognisance of contexts like globalisation. Thus, the purpose of the book is to address the sometimes unintended and unnoticed influence of globalisation on the mission of the church, with a specific focus on children, youth and family. For this purpose, the International Association for Mission Studies study group for children, youth and families coming from different parts of the world decided to describe the powers, inequalities and vulnerabilities of children, youth and families in a globalised world from their specific contexts. Although the most prominent research methodology was critical literature studies, methods like autoethnographic, and empirical methods were also used. No decisions were made on a specific method of research for this publication. This publication can be viewed as an interdisciplinary and intra-disciplinary, because it deals with social sciences, anthropology, psychology, missiology, systematic theology and practical theology

Powers, inequalities and vulnerabilities

This research addresses the gap that is present in both missiology and family and youth ministry. Missiology does not focus on children and youth specifically, while this is the largest population in the developing world. On the other hand, family and youth ministry has a more pastoral than missional approach, not always taking cognisance of contexts like globalisation. Thus, the purpose of the book is to address the sometimes unintended and unnoticed influence of globalisation on the mission of the church, with a specific focus on children, youth and family. For this purpose, the International Association for Mission Studies study group for children, youth and families coming from different parts of the world decided to describe the powers, inequalities and vulnerabilities of children, youth and families in a globalised world from their specific contexts. Although the most prominent research methodology was critical literature studies, methods like autoethnographic, and empirical methods were also used. No decisions were made on a specific method of research for this publication. This publication can be viewed as an interdisciplinary and intra-disciplinary, because it deals with social sciences, anthropology, psychology, missiology, systematic theology and practical theology