Natural polymorphisms in C. elegans HECW-1 E3 ligase affect pathogen avoidance behaviour

Heritable variation in behavioural traits generally has a complex genetic basis, and thus naturally occurring polymorphisms that influence behaviour have been defined only in rare instances. The isolation of wild strains of Caenorhabditis elegans has facilitated the study of natural genetic variation in this species and provided insights into its diverse microbial ecology. C. elegans responds to bacterial infection with conserved innate immune responses and, although lacking the immunological memory of vertebrate adaptive immunity, shows an aversive learning response to pathogenic bacteria. Here, we report the molecular characterization of naturally occurring coding polymorphisms in a C. elegans gene encoding a conserved HECT domain-containing E3 ubiquitin ligase, HECW-1. We show that two distinct polymorphisms in neighbouring residues of HECW-1 each affect C. elegans behavioural avoidance of a lawn of Pseudomonas aeruginosa. Neuron-specific rescue and ablation experiments and genetic interaction analysis indicate that HECW-1 functions in a pair of sensory neurons to inhibit P. aeruginosa lawn avoidance behaviour through inhibition of the neuropeptide receptor NPR-1 (ref. 10), which we have previously shown promotes P. aeruginosa lawn avoidance behaviour. Our data establish a molecular basis for natural variation in a C. elegans behaviour that may undergo adaptive changes in response to microbial pathogens.     

Structural insight into brassinosteroid perception by BRI1

Brassinosteroids are essential phytohormones that have crucial roles in plant growth and development. Perception of brassinosteroids requires an active complex of BRASSINOSTEROID-INSENSITIVE 1 (BRI1) and BRI1-ASSOCIATED KINASE 1 (BAK1). Recognized by the extracellular leucine-rich repeat (LRR) domain of BRI1, brassinosteroids induce a phosphorylation-mediated cascade to regulate gene expression. Here we present the crystal structures of BRI1(LRR) in free and brassinolide-bound forms. BRI1(LRR) exists as a monomer in crystals and solution independent of brassinolide. It comprises a helical solenoid structure that accommodates a separate insertion domain at its concave surface. Sandwiched between them, brassinolide binds to a hydrophobicity-dominating surface groove on BRI1(LRR). Brassinolide recognition by BRI1(LRR) is through an induced-fit mechanism involving stabilization of two interdomain loops that creates a pronounced non-polar surface groove for the hormone binding. Together, our results define the molecular mechanisms by which BRI1 recognizes brassinosteroids and provide insight into brassinosteroid-induced BRI1 activation.     

FAS and NF-κB signalling modulate dependence of lung cancers on mutant EGFR

Human lung adenocarcinomas with activating mutations in EGFR (epidermal growth factor receptor) often respond to treatment with EGFR tyrosine kinase inhibitors (TKIs), but the magnitude of tumour regression is variable and transient. This heterogeneity in treatment response could result from genetic modifiers that regulate the degree to which tumour cells are dependent on mutant EGFR. Through a pooled RNA interference screen, we show that knockdown of FAS and several components of the NF-κB pathway specifically enhanced cell death induced by the EGFR TKI erlotinib in EGFR-mutant lung cancer cells. Activation of NF-κB through overexpression of c-FLIP or IKK (also known as CFLAR and IKBKB, respectively), or silencing of IκB (also known as NFKBIA), rescued EGFR-mutant lung cancer cells from EGFR TKI treatment. Genetic or pharmacologic inhibition of NF-κB enhanced erlotinib-induced apoptosis in erlotinib-sensitive and erlotinib-resistant EGFR-mutant lung cancer models. Increased expression of the NF-κB inhibitor IκB predicted for improved response and survival in EGFR-mutant lung cancer patients treated with EGFR TKI. These data identify NF-κB as a potential companion drug target, together with EGFR, in EGFR-mutant lung cancers and provide insight into the mechanisms by which tumour cells escape from oncogene dependence.     

多孔介质太阳能吸热器的非稳态传热

为了研究塔式太阳能多孔介质吸热器的非稳态传热特性,建立了该吸热器的非稳态传热模型,通过最小二乘拟合提出适合该类型吸热器多孔介质的体积对流换热系数模型,采用数值方法求解,分别分析典型的非稳态无量纲温度场以及平均颗粒直径、孔隙率、厚度与入口空气速度对非稳态无量纲温度场的影响.结果表明:为了减小吸热器的热应力破坏,相关参数选...     

A New Theoretical Framework of Pyramid Markov Processes for Blockchain Selfish Mining

In this paper,we provide a new theoretical framework of pyramid Markov processes to solve some open and fundamental problems of blockchain selfish mining under ...     

浅析转型期图书馆传统服务和现代服务的关系

针对图书馆的服务在转型期发生的变化,在短时期内,图书馆传统服务和现代服务将并存、相互影响、相互补充、协同发展。只有正确对待传统服务与现代服务的关系,才能把图书馆事业不断推向更高的层次。     

基于轻小型无人机雷达的植被高度反演方法

针对目前主流雷达传感器难以满足轻小型无人机载荷需要,且存在着数据获取成本高及算法模型复杂的问题,在自行研制的一种高度集成、轻量化且具有高可靠性的轻小型无人机雷达系统基础上,发展了一种植被高度信息反演新方法。该方法中使用二维滤波抑制直耦波能量,基于剩余图像熵的自适应主元分析去噪方法解决传统方法主元选择不稳定的问题,并基于互相关信息的后向投影算法进一步增强目标信号,最后应用Sobel算子提取植被高度。实验结果表明,该方法反演得到的植被高度和验证数据的相关性达到0.92,均方根误差可达1.28 m。     

浅谈桥面铺装病害问题的成因及防治

桥面铺装是车辆直接作用的部分,要求有一定的强度,防止开裂,并保证耐磨.文章对部分桥梁的桥面铺装出现不规则的网状裂缝,较规则的纵向、横向裂缝及较严重的碎裂等病害,分析探讨了病害产生的设计和施工方面的原因,并提出了病害的防治措施.     

战术数据链作战效能仿真

战术数据链是C4ISR系统的重要组成部分,其作战效能的评估是我军数据链系统发展中迫切需要解决的关键问题.监视是战术数据链的主要作战任务.讨论了战术数据链监视效能评估指标,建立了战术数据链监视效能仿真模型,利用对美军11号链的研究实例说明了战术数据链作战效能仿真研究的方法.建立的仿真模型和研究方法对战术数据链建设具有指导意义.