DLGCN:基于图卷积网络的药物-lncRNA[]关联预测

为实现高通量识别新的药物-长链非编码RNA(Long non-coding RNA, lncRNA)关联,本文提出了一种基于图卷积网络模型来识别潜在药物-lncRNA关联的方法DLGCN(Drug-LncRNA graph convolution network)。首先,基于药物的结构信息和lncRNA的序列信息分别构建了药物-药物和lncRNA-lncRNA相似性网络,并整合实验证实的药物-lncRNA关联构建了药物-lncRNA异质性网络。然后,将注意力机制和图卷积运算应用于该网络中,学习药物和lncRNA的低维特征,基于整合的低维特征预测新的药物-lncRNA关联。通过效能评估,DLGCN的受试者工作特性曲线下面积(Area under receiver operating characteristic, AUROC)达到0.843 1,优于经典的机器学习方法和常见的深度学习方法。此外,DLGCN预测到姜黄素能够调控lncRNA MALAT1的表达,已被最近的研究证实。DLGCN能够有效预测药物-lncRNA关联,为肿瘤治疗新靶点的识别和抗癌药物的筛选提供了重要参考。     

冀西北坝上半干旱区南瓜油葵间作的水分效应

针对冀西北高原水源匮乏、利用低效问题,于2009-2010年在农业部张北农业资源与生态环境重点野外观测试验站通过南瓜//油葵不同间作群体结构试验,探讨了该区南瓜水分高效的种植方式。试验设南瓜单作（Sp）,南瓜行间作1行油葵（IC1）,南瓜行间作2行油葵（IC2）和油葵单作（So）4个处理。结果表明,南瓜行间种植两行油葵（IC2）在南瓜生长中后期出现了油葵与南瓜争夺水分的现象,而南瓜行间种植一行油葵（IC1）无此现象。各处理间水量平衡各分量有较大的差异,在整个生育时期降雨量为201.6mm的情况下,渗漏量占的比重非常小,并且土壤蓄水量变化均为负值,绝大部分水分都是以气态水蒸散掉,但不同间作方式蒸散失水量不同,其中IC1较So、Sp和IC2分别少散失土壤水分36.33%、19.00%和34.87%。得益于油葵的偏利效应使南瓜经济产量下降30.00% ~71.42%,而间种油葵单株产量相对单作田提高190.71%~ 241.26%,虽其土地当量比LER和水分当量比WER分别达1.08~1.22和1.07~1.26,但IC1复合群体的经济效益只能与南瓜单作田持平,其他处理明显低于单作南瓜。在冀西北高原雨养背景下,稀植高效的南瓜单作生产能够实现对区域水资源的高效利用。     

科尔沁沙地湖泊消涨对气候变化的响应

湖泊是受气候变化影响显著的地理单元之一,不同地区湖泊消涨与气候变化关系的分析是理解陆地水文过程对未来气候变化响应的关键之一。对干旱、半干旱地区而言,湖泊消涨对气候变化的响应是干旱区生态保护和未来可持续发展的重要指征。气候变化对湖泊的影响研究在不同的区域已有较多的研究,但是针对湖泊群且基于湖泊大小分级和不同降水强度的对应研究还很鲜见。有鉴于此,作者在RS和GIS技术支持下,采用湖泊大小和降水强度分级的方法,分析了科尔沁沙地湖泊群消涨与气候变化的关系。在1971-2010年间,年均气温波动升高和降水量波动减少是该区域的主要气候变化特点。从5年移动平均分析来看,1990年是气温变化的转折点,1991-2010年的平均气温7.36（?0.55）℃,高于全球同期平均增温0.52℃。在1975-2009年间,科尔沁沙地湖泊面积和数量的变化趋势呈抛物线型减少,在1995年湖泊面积与数量最高。进入21世纪,湖泊面积萎缩、数量减少呈明显的加快趋势。到2009年,面积>0.05km2湖泊数量仅为81个,不足高峰期（1995年）的11%;湖泊总面积为4375.0hm2,不到1995年的26%。本研究表明,湖泊消涨主要受到年降水量波动影响,与年内降水分布格局无关,气温变化的影响不显著。     

Protein kinase C delta null mice exhibit structural alterations in articular surface,intra-articular and subchondral compartments

IntroductionStructural alterations in intra-articular and subchondral compartments are hallmarks of osteoarthritis, a degenerative disease that causes pain and disability in the aging population. Protein kinase C delta (PKC-δ) plays versatile functions in cell growth and differentiation, but its role in the articular cartilage and subchondral bone is not known.MethodsHistological analysis including alcian blue, safranin O staining and fluorochrome labeling were used to reveal structural alterations at the articular cartilage surface and bone–cartilage interface in PKC-δ knockout (KO) mice. The morphology and organization of chondrocytes were studied using confocal microscopy. Glycosaminoglycan content was studied by micromass culture of chondrocytes of PKC-δ KO mice.ResultsWe uncovered atypical structural demarcation between articular cartilage and subchondral bone of PKC-δ KO mice. Histology analyses revealed a thickening of the articular cartilage and calcified bone–cartilage interface, and decreased safranin O staining accompanied by an increase in the number of hypertrophic chondrocytes in the articular cartilage of PKC-δ KO mice. Interestingly, loss of demarcation between articular cartilage and bone was concomitant with irregular chondrocyte morphology and arrangement. Consistently, in vivo calcein labeling assay showed an increased intensity of calcein labeling in the interface of the growth plate and metaphysis in PKC-δ KO mice. Furthermore, in vitro culture of chondrocyte micromass showed a decreased alcian blue staining of chondrocyte micromass in the PKC-δ KO mice, indicative of a reduced level of glycosaminoglycan production.ConclusionsOur data imply a role for PKC-δ in the osteochondral plasticity of the interface between articular cartilage and the osteochondral junction.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0720-4) contains supplementary material, which is available to authorized users.     

Functional comparison of metallothioneins MTT1 and MTT2 from Tetrahymena thermophila

Metallothioneins MTT1 and MTT2 from Tetrahymena thermophila have been characterized. The MTT1 contains mainly characteristic Cys-Cys-Cys and Cys-Cys clusters, but MTT2 contains mainly Cys-X-Cys cluster. Cd₁₆-MTT1 mainly consists of α-helix and β-turns, in contrast, Cd₁₁-MTT2 mainly consists of random coils. Reaction of Cd₁₆-MTT1 and Cd₁₁-MTT2 with nitric oxide leads to intramolecular disulfide bond formation, respectively. Binding stabilities of Cd²⁺, Hg²⁺ and Zn²⁺ to MTT1 are stronger than those to MTT2. Cu²⁺ can not replace Cd²⁺ from Cd₁₆-MTT1 complex, but can replace Cd²⁺ from Cd₁₁-MTT2 complex. The analysis of qRT-PCR revealed MTT2 mRNA levels were 31-fold higher than those of MTT1 under basal conditions. These results further suggest MTT1 possibly play a role in the detoxification of heavy metal ions, and MTT2 may be involved in the homeostasis of copper ions.     

Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder characterized by smooth-muscle tumors of the skin and uterus and/or renal cancer. Although the identification of germline mutations in the fumarate hydratase (FH) gene in European families supports it as the susceptibility gene for HLRCC, its role in families in North America has not been studied. We screened for germline mutations in FH in 35 families with cutaneous leiomyomas. Sequence analysis revealed mutations in FH in 31 families (89%). Twenty different mutations in FH were identified, of which 18 were novel. Of these 20 mutations, 2 were insertions, 5 were small deletions that caused frameshifts leading to premature truncation of the protein, and 13 were missense mutations. Eleven unrelated families shared a common mutation: R190H. Eighty-one individuals (47 women and 34 men) had cutaneous leiomyomas. Ninety-eight percent (46/47) of women with cutaneous leiomyomas also had uterine leiomyomas. Eighty-nine percent (41/46) of women with cutaneous and uterine leiomyomas had a total hysterectomy, 44% at age < or =30 years. We identified 13 individuals in 5 families with unilateral and solitary renal tumors. Seven individuals from four families had papillary type II renal cell carcinoma, and another individual from one of these families had collecting duct carcinoma of the kidney. The present study shows that mutations in FH are associated with HLRCC in North America. HLRCC is associated with clinically significant uterine fibroids and aggressive renal tumors. The present study also expands the histologic spectrum of renal tumors and FH mutations associated with HLRCC.     

一株抗锰土壤芽胞杆菌的分离鉴定与生物学活性分析

从山东崅屿采集的黄棕壤中分离得到一株具有抗Mn(Ⅱ)和Mn(Ⅱ)氧化双重活性的芽胞杆菌,其最高Mn(Ⅱ)耐受浓度达到130mmol/L,对Mn(Ⅱ)的氧化活性为3.3μmol/(L·d)。通过个体形态与培养特征观测、生理生化反应、G+Cmol%测定和16SrDNA序列比对分析等鉴定,确定该菌株为巨大芽胞杆菌(Bacillus megaterium),命名为MB283。该菌株在添加Mn(Ⅱ)(10mmol/L)条件下比不添加Mn(Ⅱ)表现出相对较快的生长速率。采用高温培养并结合0.01%SDS处理,从MB283菌株筛选到一株发生内生质粒消除的突变株MB287,具有与野生菌株类似的锰耐受活性,且对Mn(Ⅱ)的氧化活性与野生菌株相比无明显改变,表明野生菌株MB283中与锰抗性和锰氧化相关的基因可能是定位于该菌的染色体上。     

Development of highly polymorphic SNP markers from the complexity reduced portion of maize [Zea mays L.] genome for use in marker-assisted breeding

The duplicated and the highly repetitive nature of the maize genome has historically impeded the development of true single nucleotide polymorphism (SNP) markers in this crop. Recent advances in genome complexity reduction methods coupled with sequencing-by-synthesis technologies permit the implementation of efficient genome-wide SNP discovery in maize. In this study, we have applied Complexity Reduction of Polymorphic Sequences technology (Keygene N.V., Wageningen, The Netherlands) for the identification of informative SNPs between two genetically distinct maize inbred lines of North and South American origins. This approach resulted in the discovery of 1,123 putative SNPs representing low and single copy loci. In silico and experimental (Illumina GoldenGate (GG) assay) validation of putative SNPs resulted in mapping of 604 markers, out of which 188 SNPs represented 43 haplotype blocks distributed across all ten chromosomes. We have determined and clearly stated a specific combination of stringent criteria (>0.3 minor allele frequency, >0.8 GenTrainScore and >0.5 Chi_test100 score) necessary for the identification of highly polymorphic and genetically stable SNP markers. Due to these criteria, we identified a subset of 120 high-quality SNP markers to leverage in GG assay-based marker-assisted selection projects. A total of 32 high-quality SNPs represented 21 haplotypes out of 43 identified in this study. The information on the selection criteria of highly polymorphic SNPs in a complex genome such as maize and the public availability of these SNP assays will be of great value for the maize molecular genetics and breeding community.