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...     

地应力测量非弹性应变恢复法在某金属矿的应用

为获得某金属矿深部岩体地应力分布特征,采用非弹性应变恢复法,选取该矿同一勘探线附近距地表埋深615 m、665 m、715 m三个水平进行现场地应力测量。通过分析3个水平各测点地应力测量结果,得到该矿区地应力分布规律。该矿区最大主应力和最小主应力均为近水平主应力,中间主应力为近垂向的应力;3个水平的最大水平主应力方向基本一致,方位角为101°～130°。主应力的大小随深度呈线性增长。近水平应力大于近垂向应力,表明该矿浅部地壳应力占主导地位的是水平构造应力。两个相邻样品的非弹性应变恢复法地应力测量值平均差系数最大为8.33%,表明其结果具有较好的一致性,验证了非弹性应变恢复法的可靠性。     

兴义坡岗自然保护区陆生贝类资源调查及区系分析(腹足纲:前鳃亚纲;肺螺亚纲)

对贵州省兴义市坡岗自然保护区进行陆生贝类资源调查,共获得标本2 954号,经鉴定得66种(8个未定种),分隶于12科32属。区系分析表明:保护区内陆生贝类以东洋界种类为主,占种类总数的89%。东洋界西南区种类,占种类总数的33%;同时也有少数古北界的种类渗透,占种类总数的7%;广分布种类较少,仅占种类总数的4%。     

渡槽整体结构环境激励模态试验

为获得渡槽整体结构动力特性,开展单向SIMO法、双向MIMO法环境激励模态试验,选用增强频域分解法识别纵向、横向、竖向、横竖双向模态参数.结果表明:2种方法识别出的模态大多数谱峰明显、识别效果较好;纵向模态以排架结构振动为主,槽身整体平动或转动或不动;前4阶横向模态以排架结构振动为主,槽身整体平动或转动或横摇,第5阶模...     

对现代园林植物景观设计的理性思考

植物景观设计是现代园林景观设计的重要内容．针对现代园林植物景观设计中出现的问题和误区,提出了现代园林植物景观设计应遵循自然为先的原则．     

视频点播系统交互式功能的设计与实现

针对视频点播系统的交互特性,在使用MPEG标准的基础上,利用空间换效率的思想,建立Ⅰ帧文件及其索引,进而提出了单道交互式功能的调度模型,实现了类视频录像系统的交互式功能,如快进、快退、暂停、随机读取和恢复播放等．根据IP组播技术的特点,为用户建立专用的类视频录像操作的数据通道提供非单道模式下的数据传输,并利用流的分离与合并技术,给出了流共享机制下实现交互式功能的解决方案．单道交互式功能的测试显示出播放、快进和快退等状态能够进行平滑切换,达到录像机相应操作状态的效果．