Distinctive communication networks in inactive states of β2-adrenergic receptor: Mutual information and entropy transfer analysis

Mutual information and entropy transfer analysis employed on two inactive states of human beta-2 adrenergic receptor (β₂-AR) unraveled distinct communication pathways. Previously, a so-called “highly” inactive state of the receptor was observed during 1.5 microsecond long molecular dynamics simulation where the largest intracellular loop (ICL3) was swiftly packed onto the G-protein binding cavity, becoming entirely inaccessible. Mutual information quantifying the degree of correspondence between backbone-C_α fluctuations was mostly shared between intra- and extra-cellular loop regions in the original inactive state, but shifted to entirely different regions in this latest inactive state. Interestingly, the largest amount of mutual information was always shared among the mobile regions. Irrespective of the conformational state, polar residues always contributed more to mutual information than hydrophobic residues, and also the number of polar-polar residue pairs shared the highest degree of mutual information compared to those incorporating hydrophobic residues. Entropy transfer, quantifying the correspondence between backbone-C_α fluctuations at different timesteps, revealed a distinctive pathway directed from the extracellular site toward intracellular portions in this recently exposed inactive state for which the direction of information flow was the reverse of that observed in the original inactive state where the mobile ICL3 and its intracellular surroundings drove the future fluctuations of extracellular regions.     

PCR-generated conspecific sodium channel gene probe for the house fly.

A segment of the house fly (Musca domestica) homologue of the para (paralytic) sodium channel gene of Drosophila melanogaster was isolated by using mixed sequence oligonucleotide primers in the polymerase chain reaction (PCR). The specificity of the procedure was demonstrated by genomic Southern analysis using the housefly PCR amplification product as a probe and by DNA sequence analysis. The latter showed structural homology to the para gene, but not to the corresponding region of DSC1, another D. melanogaster gene with structural similarity to vertebrate sodium channel genes.     

Towards the identification of the allosteric Phe-binding site in phenylalanine hydroxylase

The enzyme phenylalanine hydroxylase (PAH) is defective in the inherited disorder phenylketonuria. PAH, a tetrameric enzyme, is highly regulated and displays positive cooperativity for its substrate, Phe. Whether Phe binds to an allosteric site is a matter of debate, despite several studies worldwide. To address this issue, we generated a dimeric model for Phe–PAH interactions, by performing molecular docking combined with molecular dynamics simulations on human and rat wild-type sequences and also on a human G46S mutant. Our results suggest that the allosteric Phe-binding site lies at the dimeric interface between the regulatory and the catalytic domains of two adjacent subunits. The structural and dynamical features of the site were characterized in depth and described. Interestingly, our findings provide evidence for lower allosteric Phe-binding ability of the G46S mutant than the human wild-type enzyme. This also explains the disease-causing nature of this mutant.     

Climate change and nesting behaviour in vertebrates: a review of the ecological threats and potential for adaptive responses

Nest building is a taxonomically widespread and diverse trait that allows animals to alter local environments to create optimal conditions for offspring development. However, there is growing evidence that climate change is adversely affecting nest‐building in animals directly, for example via sea‐level rises that flood nests, reduced availability of building materials, and suboptimal sex allocation in species exhibiting temperature‐dependent sex determination. Climate change is also affecting nesting species indirectly, via range shifts into suboptimal nesting areas, reduced quality of nest‐building environments, and changes in interactions with nest predators and parasites. The ability of animals to adapt to sustained and rapid environmental change is crucial for the long‐term persistence of many species. Many animals are known to be capable of adjusting nesting behaviour adaptively across environmental gradients and in line with seasonal changes, and this existing plasticity potentially facilitates adaptation to anthropogenic climate change. However, whilst alterations in nesting phenology, site selection and design may facilitate short‐term adaptations, the ability of nest‐building animals to adapt over longer timescales is likely to be influenced by the heritable basis of such behaviour. We urgently need to understand how the behaviour and ecology of nest‐building in animals is affected by climate change, and particularly how altered patterns of nesting behaviour affect individual fitness and population persistence. We begin our review by summarising how predictable variation in environmental conditions influences nest‐building animals, before highlighting the ecological threats facing nest‐building animals experiencing anthropogenic climate change and examining the potential for changes in nest location and/or design to provide adaptive short‐ and long‐term responses to changing environmental conditions. We end by identifying areas that we believe warrant the most urgent attention for further research.     

Honeybees establish specific sites on the comb for their waggle dances

Successful honeybee foragers perform dances on the surface of the comb where they interact with nectar receivers and dance followers. We have recorded the sites at which dances take place in large ten-frame hives and in two-frame observation hives. We find that dancing bees are most commonly found on particular combs in large hives and in particular areas on the combs in the observation hives. Although the site where dances take place may change from day to day, dancers will keep to the same site during the foraging period in any one day. Furthermore, if an established dance site is artificially relocated in the hive during the day, dancers seek these sites out before commencing their dances. We conclude that the dance sites are labelled in some way and so promote the congregation of both dancers and dance followers at the same site. Accepted: 27 November 1996     

Deregulation of ER-mitochondria contact formation and mitochondrial calcium homeostasis mediated by VDAC in fragile X syndrome

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基于空间生态集合覆盖模型的自学习禁忌搜索算法在保护区空间选址中的应用——以戴云山为例

自然保护区规划是保护生物多样性的有效方式.传统保护区规划方法只能识别物种保护的重点区域,无法科学确定保护区的适宜面积.地块选择方法基于数学模型,从规划区域中选择部分地块组成自然保护区,保护特定物种或生态系统,是缓解生态保护与开发利用矛盾的重要手段.现有地块选择法未考虑各单元生态差异,且最优化算法存在计算效率的瓶颈.本文首先构建适用于森林生态系统的生态值赋分评价体系,据此计算戴云山生态值并绘制其分布图;然后,结合生态值建立生态集合覆盖模型(ESCP),并基于ESCP嵌入空间紧凑性提出空间生态集合覆盖模型(SSCP);最后,利用寻优性能良好的自学习禁忌搜索算法(STS)搜索各保护目标下的近似最优选址方案,给出福建省戴云山现有建成区优化方案.结果表明: 戴云山生态值计算结果在空间分布上存在明显差异;ESCP比原集合覆盖模型(SCP)能产生生态值更高的选址方案;SSCP在ESCP基础上对生态值较高区域有聚集作用,且周长权重越大,聚集效果越明显;建议现保护区可向外拓展136 km²,并将西北向分布长苞铁杉的地块纳入保护区范围.研究结果为实现戴云山保护区可持续发展及土地资源优化配置提供了优化方案,也可为我国森林生态系统类型的自然保护区设计提供新思路.     

D-Cycloserine: Agonist turned antagonist

Summary D-Cycloserine can enhance activation of the NMDA receptor complex and could enhance the induction of long-term potentiation (LTP). In animals and humans, D-cycloserine can enhance performance in learning and memory tasks. This enhancing effect can disappear during repeated administration. The enhancing effects are also lost when higher doses are used, and replaced by behavioral and biochemical effects like those produced by NMDA antagonists. It has been reported that NMDA agonists, applied before or after tetanic stimulation, can block the induction of LTP. This may be the result of feedback inhibition of second messenger pathways stimulated by receptor activation. This may explain the antagonist-like effects of glycine partial agonists like D-cycloserine. In clinical trials of D-cycloserine in age-associated memory impairment (AAMI) and Alzheimer's disease, chronic treatment provided few positive effects on learning and memory. This may be due to inhibition of second messenger pathways following chronic stimulation of the receptor complex.