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.     

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%。     

基于类别不平衡的企业信用风险违约测度探索 ——以制造业上市公司为例

针对所获取的类别不平衡的深沪A股制造业上市公司财务数据,为了预测制造业上市公司信用违约情况,提出基于欠采样改进的Lasso-Logistic模型;首先通过计算WOE和IV值,剔除风险识别能力和稳定性较差的变量,接着从"数据"层面对现有的Lasso-Logistic模型进行批量欠采样处理,最后结合"算法"层面对Lasso...     

Act in contravention: a non-planar coupled electrode design utilizing "tip effect" for ultra-high areal capacity,long cycle life zinc-based batteries

Aqueous zinc-based batteries (ZBBs) have great potential as commercial energy storage devices.However,the poor cycling stability of zinc anode under high areal ...     

铝箔碎屑收集负压管仿真优化设计

针对铝箔剪切机的碎屑收集问题,该文研究基于计算流体力学(CFD)使用负压管收集方法。在分析流场压力-速度耦合分布特征的基础上,探讨了不同管路结构对双支管吸力的影响规律,并给出管路优化设计建议。仿真结果表明：设置2个挡板时,第2个支管可形成有效负压及吸力,但在第1个支管附近会形成较大的低速回流区,气流流出支管;当2个支管共用1个出口时,2个支管均可产生负压及吸力,但支管与出口距离不一致时会导致支管速度差异达72.17%;优化后的等距型管路结构的支管速度差异降低至约2%,可在支管口形成均匀吸力,满足工业需求;随着挡板高度增加,支管口速度值、支管口速度差异分别呈现增大、减小趋势;支管与主管倒角设置对气流有良好的导向作用,支管速度可提高约9.64%。     

Cystic fibrosis transmembrane conductance regulator—emerging regulator of cancer

Mutations of cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis, the most common life-limiting recessive genetic disease among Caucasians. CFTR mutations have also been linked to increased risk of various cancers but remained controversial for a long time. Recent studies have begun to reveal that CFTR is not merely an ion channel but also an important regulator of cancer development and progression with multiple signaling pathways identified. In this review, we will first present clinical findings showing the correlation of genetic mutations or aberrant expression of CFTR with cancer incidence in multiple cancers. We will then focus on the roles of CFTR in fundamental cellular processes including transformation, survival, proliferation, migration, invasion and epithelial–mesenchymal transition in cancer cells, highlighting the signaling pathways involved. Finally, the association of CFTR expression levels with patient prognosis, and the potential of CFTR as a cancer prognosis indicator in human malignancies will be discussed.     

Differentiated cells are more efficient than adult stem cells for cloning by somatic cell nuclear transfer

Since the creation of Dolly via somatic cell nuclear transfer (SCNT), more than a dozen species of mammals have been cloned using this technology. One hypothesis for the limited success of cloning via SCNT (1%-5%) is that the clones are likely to be derived from adult stem cells. Support for this hypothesis comes from the findings that the reproductive cloning efficiency for embryonic stem cells is five to ten times higher than that for somatic cells as donors and that cloned pups cannot be produced directly from cloned embryos derived from differentiated B and T cells or neuronal cells. The question remains as to whether SCNT-derived animal clones can be derived from truly differentiated somatic cells. We tested this hypothesis with mouse hematopoietic cells at different differentiation stages: hematopoietic stem cells, progenitor cells and granulocytes. We found that cloning efficiency increases over the differentiation hierarchy, and terminally differentiated postmitotic granulocytes yield cloned pups with the greatest cloning efficiency.     

中等专业学校加强档案工作建设刍议

作为纪录历史的档案文献,是党和国家的宝贵财富。学校档案工作是我国教育事业的重要组成部分,对学校教育教学管理和国家经济建设有着及其重要的作用。文章从梳理学校档案工作的概念和作用入手,对中等专业学校档案工作存在问题进行分析,提出一些加强这项工作的措施,以求科学、规范地做好中等专业学校档案工作。