Evidence that NO/cGMP/PKG signalling cascade mediates endothelium dependent inhibition of IP3R mediated Ca2+ oscillations in myocytes and pericytes of ureteric microvascular network in situ

In ureteric microvessels the antagonistic relationship between Ca²⁺ signalling in endothelium and Ca²⁺ oscillations in myocytes and pericytes of arterioles and venules involves nitric oxide (NO), but the underlying mechanisms are not well understood. In the present study we investigated the effects of carbachol and NO donor SNAP on Ca²⁺ signalling and vasomotor responses of arterioles and venules in intact urteric microvascular network in situ using confocal microscopy. Vasomotor responses of arterioles and venules induced by AVP correlated with the occurrence of Ca²⁺ oscillations in the myocytes and pericytes and were not abolished by the removal of Ca²⁺ from extracellular fluid. Carbachol-induced rise of intracellular Ca²⁺ in endothelium was accompanied by the termination of the Ca²⁺ oscillations in myocytes and pericytes. This carbachol-induced inhibitory effect on Ca²⁺ oscillations in myocytes and pericytes was reversed by ODQ, an inhibitor of soluble guanylyl cyclase (sGC) and by Rp-8-pCPT-cGMPS, an inhibitor of protein kinase G (PKG). Ca²⁺ oscillations in myocytes and pericytes were also effectively blocked by NO donor SNAP. An Inhibitory effect of SNAP was markedly enhanced by zaprinast, a selective inhibitor of cGMP-specific phosphodiesterase-5, and reversed by sGC inhibitor, ODQ and PKG inhibitor, Rp-8-pCPT-cGMPS. The cGMP analogue and selective PKG activator 8pCPT-cGMP also induced inhibition of the AVP-induced Ca²⁺ oscillations in myocytes and pericytes. SNAP had no effects on Ca²⁺ oscillations induced by caffeine in distributing arcade arterioles. Consequently, we conclude that NO- mediated inhibition of Ca²⁺ oscillations in myocytes and pericytes predominantly recruits the cGMP/PKG dependent pathway. The inhibitory effect of NO/cGMP/PKG cascade is associated with suppressed Ca²⁺ release from the SR of myocytes and pericytes selectively via the inositol triphosphate receptor (IP₃R) channels.     

Niche partitioning due to adaptive foraging reverses effects of nestedness and connectance on pollination network stability

Much research debates whether properties of ecological networks such as nestedness and connectance stabilise biological communities while ignoring key behavioural aspects of organisms within these networks. Here, we computationally assess how adaptive foraging (AF) behaviour interacts with network architecture to determine the stability of plant–pollinator networks. We find that AF reverses negative effects of nestedness and positive effects of connectance on the stability of the networks by partitioning the niches among species within guilds. This behaviour enables generalist pollinators to preferentially forage on the most specialised of their plant partners which increases the pollination services to specialist plants and cedes the resources of generalist plants to specialist pollinators. We corroborate these behavioural preferences with intensive field observations of bee foraging. Our results show that incorporating key organismal behaviours with well‐known biological mechanisms such as consumer‐resource interactions into the analysis of ecological networks may greatly improve our understanding of complex ecosystems.     

Social carry‐over effects underpin trans‐seasonally linked structure in a wild bird population

Spatial structure underpins numerous population processes by determining the environment individuals' experience and which other individuals they encounter. Yet, how the social landscape influences individuals' spatial decisions remains largely unexplored. Wild great tits (Parus major) form freely moving winter flocks, but choose a single location to establish a breeding territory over the spring. We demonstrate that individuals' winter social associations carry‐over into their subsequent spatial decisions, as individuals breed nearer to those they were most associated with during winter. Further, they also form territory boundaries with their closest winter associates, irrespective of breeding distance. These findings were consistent across years, and among all demographic classes, suggesting that such social carry‐over effects may be general. Thus, prior social structure can shape the spatial proximity, and fine‐scale arrangement, of breeding individuals. In this way, social networks can influence a wide range of processes linked to individuals' breeding locations, including other social interactions themselves.     

An ectomycorrhizal nitrogen economy facilitates monodominance in a neotropical forest

Tropical forests are renowned for their high diversity, yet in many sites a single tree species accounts for the majority of the individuals in a stand. An explanation for these monodominant forests remains elusive, but may be linked to mycorrhizal symbioses. We tested three hypotheses by which ectomycorrhizas might facilitate the dominance of the tree, Oreomunnea mexicana, in montane tropical forest in Panama. We tested whether access to ectomycorrhizal networks improved growth and survival of seedlings, evaluated whether ectomycorrhizal fungi promote seedling growth via positive plant–soil feedback, and measured whether Oreomunnea reduced inorganic nitrogen availability. We found no evidence that Oreomunnea benefits from ectomycorrhizal networks or plant–soil feedback. However, we found three‐fold higher soil nitrate and ammonium concentrations outside than inside Oreomunnea‐dominated forest and a correlation between soil nitrate and Oreomunnea abundance in plots. Ectomycorrhizal effects on nitrogen cycling might therefore provide an explanation for the monodominance of ectomycorrhizal tree species worldwide.     

Vegetation,herbivores and fires in savanna ecosystems: A network perspective

The dynamics of savanna ecosystems depends on the interplay between multiple factors such as grazing, browsing, fires, rainfall regime and interactions between grass and woody vegetation. In most modelling applications this interplay may not be fully understood because some of these drivers enter the models as dynamically independent factors. In this paper we consider such factors as dynamic variables. To analyze their interplay we focus on the structure of the interactive network of variables and exploit the properties of signed digraphs using the algorithm of Loop Analysis. Qualitative signed digraphs for the savanna ecosystem are developed and their predictions used to interpret patterns of abundance observed in case studies selected from the literature. The outcomes of this exercise unveil that: 1) the structure of the interactions is appropriate locus for the explanation of patterns observed in savannas; 2) signed digraph can help disentangling causative mechanisms by linking correlation patterns, source of change and network structure. This study highlights that central to the understanding of savanna dynamics is our ability to diagram the important relationships and understand how they interrelate with sources of variations to cause ecosystem change.     

基于深度最大输出网络的抗体种型特异性B细胞表位预测

B细胞表位研究有助于肽段疫苗研制,抗体研制以及疾病诊断和治疗研究.不同的B细胞表位诱导免疫系统产生不同的抗体种型,探索研究能够诱导特异性抗体产生的B细胞表位具有重要意义.基于二肽组成特征,利用深度最大输出网络算法训练构建三个二类分类器,分别对应诱导三种不同特异性抗体的B细胞表位,即IgA表位,IgE表位以及IgG表位.通过五折交叉验证训练和测试这三个分类器,获得AUC的值分别为0.78,0.93以及0.78.IgA表位和IgE表位分类器的预测能力优于其它IgA表位和IgE表位分类器,IgG表位分类器和其它IgG表位分类器的预测能力相当.     

Differential Expression of microRNAs and their Regulatory Networks in Skin Tissue of Liaoning Cashmere Goat during Hair Follicle Cycles

MicroRNAs (miRNAs) are endogenous small noncoding RNA molecules that negatively regulate gene expression. Herein, we investigated a selective number of miRNAs for their expression in skin tissue of Liaoning Cashmere goat during hair follicle cycles, and their intracellular regulatory networks were constructed based on bioinformatics analysis. The relative expression of six miRNAs (mir-103-3p, -15b-5p, 17-5p, -200b, -25-3p, and -30c-5p) at anagen phase is significantly higher than that at catagen and/or telogen phases. In comparison to anagen, the relative expression of seven miRNAs (mir-148a-3p, -199a-3p, -199a-5p, -24-3p, -30a-5p, -30e-5p, and -29a-3p) was revealed to be significantly up-regulated at catagen and/or telogen stages. The network analyses of miRNAs indicated those miRNAs investigated might be directly or indirectly involved in several signaling pathways through their target genes. These results provided a foundation for further insight into the roles of these miRNAs in skin tissue of Liaoning Cashmere goat during hair follicle cycles.     

中国结节性硬化症患者的临床特点及诊断现状分析

目的:回顾结节性硬化症(TSC)在中国的诊断现状,分析中国TSC患者的临床特点,促进TSC的识别、规范化诊治和管理。方法:在维普数据库、万方数据库、中国知网、中国生物医学文献数据库、PubMed数据库中全面检索2001年-2014年13年间国内外发表的关于中国患者TSC的269篇所涉及的3171例TSC患者从皮肤、神经系统、肾脏、心脏、肺等多系统的临床特点对文献进行了统计和分析,并对TSC患者遗传学方面的基因检测情况进行了归纳和总结。结果:对照2012年TSC诊断指南,在对诊断标准中主要指征的报道中,共有247篇文献对2607例TSC患者的皮肤损害进行了描述,212篇文献对2395例TSC患者的神经系统损害的影像学表现进行了报道,有55篇文献报道了对348例患者进行的眼底检查中发现多发性视网膜错构瘤84例,32篇文献报道了对282例患者进行的心脏彩超检查中发现162例心脏横纹肌瘤,45篇文献在对282例患者进行的胸片检查、20篇文献在对36例患者进行的胸部CT检查中共发现淋巴管肌瘤病50例。在98篇文献报道的对696例患者进行的肾脏超声检查、51篇文献报道的对221例患者进行的肾脏CT检查和2篇文献报道的对2例患者进行的肾脏MRI检查中共发现肾脏血管平滑肌脂肪瘤416例;在58篇文献报道的对586例TSC患者进行的肝脏超声检查、30篇文献报道的对104例患者进行的腹部CT检查、2篇文献报道的对3例患者进行的腹部MRI检查中共发现肝脏血管平滑肌脂肪瘤141例。在诊断标准中的次要指征的报道中,对多发性肾囊肿的报道最多,而对牙釉质凹陷、Confetti皮损的描述却几乎缺失。在其他临床表现的研究中,癫痫的相关文献最多,有关智力评估的文献尚缺乏客观的智力评估标准。遗传学基因检测逐渐成为近几年文献报道的热点。结论:在过去13年间,中国医生对TSC的诊治作出了很大贡献,但诊断过程中仍存在对疾病认识的不足和对全局观念的缺乏,推广新版指南的诊断标准对于中国医生是十分有意义的。     

Plasma Proteome Signature of Sepsis: a Functionally Connected Protein Network

Sepsis is an extreme host response to infection that leads to loss of organ function and cardiovascular integrity. Mortality from sepsis is on the rise. Despite more than three decades of research and clinical trials, specific diagnostic and therapeutic strategies for sepsis are still absent. The use of LFQ‐ and TMT‐based quantitative proteomics is reported here to study the plasma proteome in five mouse models of sepsis. A knowledge‐based interpretation of the data reveals a protein network with extensive connectivity through documented functional or physical interactions. The individual proteins in the network all have a documented role in sepsis and are known to be extracellular. The changes in protein abundance observed in the mouse models of sepsis have for the most part the same directionality (increased or decreased abundance) as reported in the literature for human sepsis. This network has been named the Plasma Proteome Signature of Sepsis (PPSS). The PPSS is a quantifiable molecular readout that can supplant the current symptom‐based approach used to diagnose sepsis. This type of molecular interpretation of sepsis, its progression, and its response to therapeutic intervention are an important step in advancing our understanding of sepsis, and for discovering and evaluating new therapeutic strategies.     

Comparative Nuclear Proteomics Analysis Provides Insight into the Mechanism of Signaling and Immune Response to Blast Disease Caused by Magnaporthe oryzae in Rice

Modulation of plant immune system by extrinsic/intrinsic factors and host‐specific determinants fine‐tunes cellular components involving multiple organelles, particularly nucleus to mount resistance against pathogen attack. Rice blast, caused by hemibiotrophic fungus Magnaporthe oryzae, is one of the most devastating diseases that adversely affect rice productivity. However, the role of nuclear proteins and their regulation in response to M. oryzae remains unknown. Here, the nucleus‐associated immune pathways in blast‐resistant rice genotype are elucidated. Temporal analysis of nuclear proteome is carried out using 2‐DE coupled MS/MS analysis. A total of 140 immune responsive proteins are identified associated with nuclear reorganization, cell division, energy production/deprivation, signaling, and gene regulation. The proteome data are interrogated using correlation network analysis that identified significant functional modules pointing toward immune‐related coinciding processes through a common mechanism of remodeling and homeostasis. Novel clues regarding blast resistance include nucleus‐associated redox homeostasis and glycolytic enzyme–mediated chromatin organization which manipulates cell division and immunity. Taken together, the study herein provides evidence that the coordination of nuclear function and reprogramming of host translational machinery regulate resistance mechanism against blast disease.