杨树泛基因组构建与基因组变异分析

【目的】杨树是重要的速生用材、生态防护和碳汇造林树种,也是林木遗传研究的模式树种。开展杨树泛基因组构建与基因组变异分析,可为杨树精准育种和林木泛基因组研究提供理论先导。【方法】 以公开发表的高质量杨树基因组序列为基础,分析不同类型的序列变异,总结变异特征,并构建基于基因和图形结构的杨树泛基因组。【结果】 本研究收集到8个杨属树种和3个二倍体或三倍体杨树杂交品种的基因组序列,3个杂交品种包含7个单倍型亚基因组序列,较好地代表了杨树4个组派的基因组特征。分析结果表明,杨树基因组间存在较多大的结构变异。在基于基因的泛基因组中,共线核心基因、非共线核心基因、次核心基因、非必需基因、特异基因占比分别为12.5%、34.9%、31.4%、16.5%、4.7%。其中,非必需基因在功能上具有较高的多样性。以基因组序列变异为基础构建杨树图形结构泛基因组,大幅提升2代测序数据的变异检测效果。通过泛基因组变异热点分析,鉴定出2个与物候关联的基因位点。【结论】 杨属基因组中存在大量染色体重排,进而增加了基因调控的多样性。杨树组/派间的基因组结构变异可能与物候适应存在关联。基于林木基因组序列的复杂性,在林木泛基因组研究中应注意基因组整合范围与研究目标相匹配,结合基因泛基因组和图形结构泛基因组结果,综合解析林木的遗传变异规律和物种演化特征。     

Comparative analyses of multi-species sequences from targeted genomic regions

The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.     

基于AdaBoost的基因组缺失变异综合检测策略

针对基因组缺失变异检测中测序序列分裂比对方法所存在的假发现率较高的问题,提出了一种基于检测理论和AdaBoost的综合检测策略.首先,对配对末端测序序列进行初次映射和二次分裂比对,得到1 bp解析度的候选缺失变异集合,并使得该集合中包含尽可能多的候选变异;然后,依据配对末端测序序列映射分析、测序序列分裂比对和测序序列映射深度分析3类检测方法的基本原理,在2次比对结果中提取与缺失变异相关的序列特征;最后,以具有高泛化性能的AdaBoost神经网络集成模型为判别模型,筛除候选集中的伪阳性结果,从而得到最终结果集.实验结果表明,相对于传统的测序序列分裂比对方法,所提策略能够在几乎不损失检测敏感度的前提下更加有效地降低假发现率.     

A novel retinoblastoma therapy from genomic and epigenetic analyses

Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated. To identify the mutations that cooperate with RB1 loss, we performed whole-genome sequencing of retinoblastomas. The overall mutational rate was very low; RB1 was the only known cancer gene mutated. We then evaluated the role of RB1 in genome stability and considered non-genetic mechanisms of cancer pathway deregulation. For example, the proto-oncogene SYK is upregulated in retinoblastoma and is required for tumour cell survival. Targeting SYK with a small-molecule inhibitor induced retinoblastoma tumour cell death in vitro and in vivo. Thus, retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss.     

Advanced primary peritoneal carcinoma: clinicopathological and prognostic factor analyses

Objective： To investigate the factors favoring a positive prognosis for advanced primary peritoneal carcinoma （PPC）. Methods： Twenty-four cases meeting the criteria for PPC were analyzed retrospectively for the clinicopathologic profiles. Immunohistochemistry was used to determine the expressions of p53, Top2α, Ki-67 and Her-2/neu. Then all these clinicopathological factors and molecular markers were correlated with the prognosis. Results： There were 15 cases of primary peritoneal serous papillary carcinoma （PPSPC）, 6 cases of mixed epithelial carcinoma （MEC） and 3 cases of malignant mixed Mullerian tumor （MMMT）. All patients underwent cytoreductive surgery with optimal debulking achieved in 3 cases. Among those receiving first-line chemotherapy, 13 patients received the TP regimen （paclitaxel-cisplatin or carboplatin） and 7 patients received the PAC regimen （cisplatin-doxorubicin-cyclophosphamide）. The median overall survival of all patients was 42 months, while the breakdown for survival time for patients with PPSPC, MMT and MEC was 44, 13 and 19 months, respectively. The expressions of p53, Top2α and Ki-67 were all demonstrated in 11 cases respectively. None showed the expression of Her-2/neu. There were significant differences in the median survival between patients with PPSPC and those with MMMT （44 months vs 13 months, P〈0.05）, also between patients receiving TP combination and those receiving the PAC regimen （75 months vs 28 months, P〈0.05）. Another significant difference in the median progression-free survival （PFS） was identified between patients with positive p53 immunostaining and those with negative p53 immunostaining （15 months vs 47 months, P〈0.05）, whereas age, menopausal status, residual tumor size and the other molecular factors did not significantly impact survival. Conclusion： Patients with PPC should be treated with a comprehensive management plan including appropriate cytoreductive surgery and responsive chemotherapy. Overestimating an o     

黄瓜花叶病毒小青菜分离物RNA3全长序列分析

对侵染十字花科小青菜的黄瓜花叶病毒YN分离物（CMV-YN）RNA3进行全长克隆和序列分析．CMV-YNRNA3全长2220nt,分别编码279个氨基酸的3a蛋白和218个氨基酸的CP．序列同源性比较结果如下;CMV-YNRNA3核苷酸及其编码蛋白的氨基酸序列与亚组IA株系CMV-Fny、亚组IB株系CMV-Nt9、亚组Ⅱ株系CMV-Q的同源性,RNA3序列分别为92．7％、96．7％、74．2％,3a蛋白氨基酸序列分别为96．4％、98．6％、83．2％,CP氨基酸序列分别为97．7％、98．2％、83．1％．该结果表明CMV-YN与亚组IB株系CMV-Nt9的同源关系更密切．对CP核苷酸序列的系统进化树分析表明：CMV-YN归属于亚组IB,本研究为首次报道侵染我国十字花科植物的CMV基因组序列．     

54例累及颅底的鼻咽癌、脊索瘤及垂体瘤的MRI影像

目的:探讨累及颅底的鼻咽癌、脊索瘤和垂体瘤MRI影像特点,以期提高对其鉴别诊断水平.方法:搜集经病理证实的累及颅底的28例鼻咽癌、10例脊索瘤及16例垂体瘤,比较分析其MRI表现. 结果:本组鼻咽癌在T1WI上有10例表现为等信号,18例表现为稍低信号;在T2WI上10例表现为等信号,18例表现为稍高信号,形态不规则,边界不清.脊索瘤10例在T1WI上均表现为信号欠均匀,以低信号为主,混杂有等信号,其中有1例伴有斑片状高信号影;T2WI上均表现为不均匀明显高信号,为分叶状肿块,边界较为清楚.垂体瘤16例在T1WI上表现为均匀等信号或稍低信号,边界清楚,其中4例肿瘤内有出血.28例鼻咽癌的肿瘤中心部位均位于一侧的鼻咽侧壁;脊索瘤10例中有9例肿瘤的中心部位在颅底中线处的斜坡,1例肿瘤的中心部位在左侧枕骨、颞骨交界区;16例垂体瘤的肿瘤中心部位位于蝶鞍.结论:根据MRI信号特点、肿瘤中心点部位和边缘情况,大多数累及颅底的鼻咽癌、脊索瘤和垂体瘤可以作出正确诊断.     

移动电子商务浅析

Internet、移动通信技术和其他技术的完美结合创造了移动电子商务,在未来的全球数字经济中,移动电子商务将可以随时随地为消费者提供安全的电子商务服务,因此必将带来电子商务领域的一场革命,移动电子商务必将具有更广阔应用前景.     

A genomic view of immunology

The outstanding problems facing immunology are whole system issues: curing allergic and autoimmune disease and developing vaccines to stimulate stronger immune responses against pathogenic organisms and cancer. We hope that the human genome sequence will reveal the molecular checks and balances that ensure both an effective immunogenic response against pathogenic microorganisms and a suitably tolerogenic response to self antigens and innocuous environmental antigens. Three synergistic approaches--sequence homology searches, messenger RNA expression profiling on microarrays, and mutagenesis in mice--provide the best opportunities to reveal, in the genome sequence, key proteins and pathways for targeting by new immunomodulatory treatments.     

The susceptibility gene for familial nasopharyngeal carcinoma is mapped on chromosome 4p11-p14 by haplotype analyses

In our previous study, one candidate susceptibility locus for familial nasopharyngeal carcinoma (NPC) has been defined to a 14.21-cM region on 4p15.1-q12, whereas the distal minimum boundary of this region remained to be further determined in respect that the two markers D4S2996 and D4S428 were uninformative. In the present study, we carried out a haplotype analysis to identify the exact boundary by using the combination of a set of microsatellite markers and single nucleotide polymorphism (SNP) markers in two major NPC families. We defined the exact distal boundary between D4S1577 and D4S3347, and consequently shortened the susceptibifity locus to an 8.29-cM segment on 4pll-p14.     

博客与化学综合实践活动课程的整合研究

本文主要探索信息技术与课程整合的新模式,尝试将网络新技术——博客与化学综合实践活动课程进行整合,提出了整合的依据以及具体做法。     

蚂蚁DNA提取方法的研究

针对不同体型的蚂蚁,提出了一套实用的总DNA提取方法.该方法依照虫体大小,分别采用冰冻固定后捣碎和剪刀剪碎两种方法破碎虫体,使材料利用充分,提高了提取效率.探讨了组织匀浆、DNA沉淀及溶解等实验中常见问题.结果表明,采用盐析法提取DNA,较传统的酚-氯仿抽提法简单、高效.     

集成光子学

光通讯的优势在于纳米波导结构和新材料及结构的耦合，本书主要介绍集成光子学这一主题，侧重介绍了光波导和数值模拟技术，内容包括电磁理论的基本原理、波导、波导模式的模拟和光子结构。     

Dissecting the genomic complexity underlying medulloblastoma

Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently identified. WNT tumours, showing activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis. Group 3 and 4 tumours are molecularly less well characterized, and also present the greatest clinical challenges. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of what are, to our knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 and 4 patients.     

Organizational challenges in clinical genomic research

Genome sequence data are enabling clinical genomic investigation, in which the characteristics of human patients are explored using comprehensive inventories of biomolecules. Successful investigators must navigate rapid technological change, collect and analyse large volumes of data, and engage systems of clinical care. Such projects will increasingly rely on fully integrated multidisciplinary teams, demanding new organizational models in academic biomedical research.     

连杆安全性分析

文章利用AVL EXCITE、MSC Nastran、Abaqus和Ncode软件,对某汽油机连杆进行大头轴承弹性液体动力学分析、强度分析与疲劳分析,为连杆设计开发提供安全评价支持.