在比尔人遗传亲和力，KOL和良好的史诗罗摩衍那提到

by Gyaneshwer Chaubey, Anurag Kadian, Saroj Bala, Vadlamudi Raghavendra Rao

Kol, Bhil and Gond are some of the ancient tribal populations known from the Ramayana, one of the Great epics of India. Though there have been studies about their affinity based on classical and haploid genetic markers, the molecular insights of their relationship with other tribal and caste populations of extant India is expected to give more clarity about the the question of continuity vs. discontinuity. In this study, we scanned >97,000 of single nucleotide polymorphisms among three major ancient tribes mentioned in Ramayana, namely Bhil, Kol and Gond. The results obtained were then compared at inter and intra population levels with neighboring and other world populations. Using various statistical methods, our analysis suggested that the genetic architecture of these tribes (Kol and Gond) was largely similar to their surrounding tribal and caste populations, while Bhil showed closer affinity with Dravidian and Austroasiatic (Munda) speaking tribes. The haplotype based analysis revealed a massive amount of genome sharing among Bhil, Kol, Gond and with other ethnic groups of South Asian descent. On the basis of genetic component sharing among different populations, we anticipate their primary founding over the indigenous Ancestral South Indian (ASI) component has prevailed in the genepool over the last several thousand years.

• http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0127655

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从冰川到桑拿：不同的温度条件下具有共同的和新的真菌响应下的人类病原菌黑木耳皮炎外瓶霉RNA seq

by Barbara Blasi, Hakim Tafer, Donatella Tesei, Katja Sterflinger

Exophiala dermatitidis (Wangiella dermatitidis) belongs to the group of the so-called black yeasts. Thanks in part to its thick and strongly melanized cell walls, E. dermatitidis is extremely tolerant to various kinds of stress, including extreme pH, temperature and desiccation. E. dermatitidis is also the agent responsible for various severe illnesses in humans, such as pneumonia and keratitis, and might lead to fatal brain infections. Due to its association with the human environment, its poly-extremophilic lifestyle and its pathogenicity in humans, E. dermatitidis has become an important model organism. In this study we present the functional analysis of the transcriptional response of the fungus at 1°C and 45°C, in comparison with that at 37°C, for two different exposition times, i.e. 1 hour and 1 week. At 1°C, E. dermatitidis uses a large repertoire of tools to acclimatize, such as lipid membrane fluidization, trehalose production or cytoskeleton rearrangement, which allows the fungus to remain metabolically active. At 45°C, the fungus drifts into a replicative state and increases the activity of the Golgi apparatus. As a novel finding, our study provides evidence that, apart from the protein coding genes, non-coding RNAs, circular RNAs as well as fusion-transcripts are differentially regulated and that the function of the fusion-transcripts can be related to the corresponding temperature condition. This work establishes that E. dermatitidis adapts to its environment by modulating coding and non-coding gene transcription levels and through the regulation of chimeric and circular RNAs.

• http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0127103

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核小体定位及其在植物基因表达的影响因素[研究]

Nucleosome positioning influences the access of transcription factors (TFs) to their binding sites and gene expression. Studies in plant, animal, and fungal models demonstrate similar nucleosome positioning patterns along genes and correlations between occupancy and expression. However, the relationships among nucleosome positioning, cis-regulatory element accessibility, and gene expression in plants remain undefined. Here, we showed that plant nucleosome depletion occurs on specific 6-mer motifs and this sequence-specific nucleosome depletion is predictive of expression levels. Nucleosome depleted regions in Arabidopsis thaliana tend to have higher G/C content, unlike yeast, and are centered on specific G/C-rich 6-mers, suggesting that intrinsic sequence properties, such as G/C content, cannot fully explain plant nucleosome positioning. These 6-mer motif sites showed higher DNase I hypersensitivity and are flanked by strongly phased nucleosomes, consistent with known TF binding sites. Intriguingly, this 6-mer specific nucleosome depletion pattern occurs not only in promoter but also in genic regions and is significantly correlated with higher gene expression, a phenomenon also found in rice but not in yeast. Among 6-mer motifs enriched in genes responsive to treatment with the defense hormone jasmonate, there are no significant changes in nucleosome occupancy, suggesting that these sites are potentially pre-conditioned to enable rapid response without changing chromatin state significantly. Our study provides the first global assessment of the joint contribution of nucleosome occupancy and 6-mer motifs that are likely cis-elements for control of gene expression. Our findings pave the way for further understanding the impact of chromatin state on plant transcriptional regulatory circuits.

• http://genome.cshlp.org/cgi/reprint/gr.188680.114v1?rss=1

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< > > < /艰难梭菌和<它> > < /污泥梭状芽孢杆菌比较基因组和表型分析，两相关病原体的宿主组织的偏好不同

Background: Clostridium difficile and C. sordellii are two anaerobic, spore forming, gram positive pathogens with a broad host range and the ability to cause lethal infections. Despite strong similarities between the two Clostridial strains, differences in their host tissue preference place C. difficile infections in the gastrointestinal tract and C. sordellii infections in soft tissues. Results: In this study, to improve our understanding of C. sordellii and C. difficile virulence and pathogenesis, we have performed a comparative genomic and phenomic analysis of the two. The global phenomes of C. difficile and C. sordellii were compared using Biolog Phenotype microarrays. When compared to C. difficile, C. sordellii was found to better utilize more complex sources of carbon and nitrogen, including peptides. Phenotype microarray comparison also revealed that C. sordellii was better able to grow in acidic pH conditions. Using next generation sequencing technology, we determined the draft genome of C. sordellii strain 8483 and performed comparative genome analysis with C. difficile and other Clostridial genomes. Comparative genome analysis revealed the presence of several enzymes, including the urease gene cluster, specific to the C. sordellii genome that confer the ability of expanded peptide utilization and survival in acidic pH. Conclusions: The identified phenotypes of C. sordellii might be important in causing wound and vaginal infections respectively. Proteins involved in the metabolic differences between C. sordellii and C. difficile should be targets for further studies aimed at understanding C. difficile and C. sordellii infection site specificity and pathogenesis.

• http://www.biomedcentral.com/1471-2164/16/448

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共培养和并存的两种鱼类病原菌<它> <它>一较少的转录组测序和<它> Aliivibrio wodanis < / >

Background: Aliivibrio wodanis and Moritella viscosa have often been isolated concurrently from fish with winter-ulcer disease. Little is known about the interaction between the two bacterial species and how the presence of one bacterial species affects the behaviour of the other. Results: The impact on bacterial growth in co-culture was investigated in vitro, and the presence of A. wodanis has an inhibitorial effect on M. viscosa. Further, we have sequenced the complete genomes of these two marine Gram-negative species, and have performed transcriptome analysis of the bacterial gene expression levels from in vivo samples. Using bacterial implants in the fish abdomen, we demonstrate that the presence of A. wodanis is altering the gene expression levels of M. viscosa compared to when the bacteria are implanted separately. Conclusions: From expression profiling of the transcriptomes, it is evident that the presence of A. wodanis is altering the global gene expression of M. viscosa. Co-cultivation studies showed that A. wodanis is impeding the growth of M. viscosa, and that the inhibitorial effect is not contact-dependent.

• http://www.biomedcentral.com/1471-2164/16/447

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比较转录组学分析揭示了在寒冷的应激反应，香蕉和大蕉之间的关键差异表达基因

Background: Banana and plantain (Musa spp.) comprise an important part of diets for millions of people around the globe. Low temperature is one of the key environmental stresses which greatly affects the global banana production. To understand the molecular mechanism of the cold-tolerance in plantain we used RNA-Seq based comparative transcriptomics analyses for both cold-sensitive banana and cold-tolerant plantain subjected to the cold stress for 0, 3 and 6 h. Results: The cold-response genes at early stage are identified and grouped in both species by GO analysis. The results show that 10 and 68 differentially expressed genes (DEGs) are identified for 3 and 6 h of cold stress respectively in plantain, while 40 and 238 DEGs are identified respectively in banana. GO classification analyses show that the majority of DEGs identified in both banana and plantain belong to 11 categories including regulation of transcription, response to stress signal transduction, etc. A similar profile for 28 DEGs was found in both banana and plantain for 6 h of cold stress, suggesting both share some common adaptation processes in response to cold stress. There are 17 DEGs found uniquely in cold-tolerance plantain, which were involved in signal transduction, abiotic stress, copper ion equilibrium, photosynthesis and photorespiration, sugar stimulation, protein modifications etc. Twelve early responsive genes including ICE1 and MYBS3 were selected and further assessed and confirmed by qPCR in the extended time course experiments (0, 3, 6, 24 and 48 h), which revealed significant expression difference of key genes in response to cold stress, especially ICE1 and MYBS3 between cold-sensitive banana and cold-tolerant plantain. Conclusions: We found that the cold-tolerance pathway appears selectively activated by regulation of ICE1 and MYBS3 expression in plantain under different stages of cold stress. We conclude that the rapid activation and selective induction of ICE1 and MYBS3 cold tolerance pathways in plantain, along with expression of other cold-specific genes, may be one of the main reasons that plantain has higher cold resistance than banana.

• http://www.biomedcentral.com/1471-2164/16/446

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的多毛类的< > < > hermodice垂/转录组测序和注释（环节动物门，amphinomidae）

Background: The amphinomid polychaete Hermodice carunculata is a cosmopolitan and ecologically important omnivore in coral reef ecosystems, preying on a diverse suite of reef organisms and potentially acting as a vector for coral disease. While amphinomids are a key group for determining the root of the Annelida, their phylogenetic position has been difficult to resolve, and their publically available genomic data was scarce. Results: We performed deep transcriptome sequencing (Illumina HiSeq) and profiling on Hermodice carunculata collected in the Western Atlantic Ocean. We focused this study on 58,454 predicted Open Reading Frames (ORFs) of genes longer than 200 amino acids for our homology search, and Gene Ontology (GO) terms and InterPro IDs were assigned to 32,500 of these ORFs. We used this de novo assembled transcriptome to recover major signaling pathways and housekeeping genes. We also identify a suite of H. carunculata genes related to reproduction and immune response. Conclusions: We provide a comprehensive catalogue of annotated genes for Hermodice carunculata and expand the knowledge of reproduction and immune response genes in annelids, in general. Overall, this study vastly expands the available genomic data for H. carunculata, of which previously consisted of only 279 nucleotide sequences in NCBI. This underscores the utility of Illumina sequencing for de novo transcriptome assembly in non-model organisms as a cost-effective and efficient tool for gene discovery and downstream applications, such as phylogenetic analysis and gene expression profiling.

• http://www.biomedcentral.com/1471-2164/16/445

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端粒蛋白分子是一个电荷抗脚手架蛋白染色体形成的花束

Background: Chromosomes reorganise in early meiotic prophase to form the so-called telomere bouquet. In fission yeast, telomeres localise to the nuclear periphery via interaction of the telomeric protein Rap1 with the membrane protein Bqt4. During meiotic prophase, the meiotic proteins Bqt1-2 bind Rap1 and tether to the spindle pole body to form the bouquet. Although it is known that this polarised chromosomal arrangement plays a crucial role in meiotic progression, the molecular mechanisms of telomere bouquet regulation are poorly understood. Results: Here, we detected high levels of Rap1 phospho-modification throughout meiotic prophase, and identified a maximum of 35 phosphorylation sites. Concomitant phosphomimetic mutation of the modification sites suggests that Rap1 hyper-phosphorylation does not directly regulate telomere bouquet formation or dissociation. Despite the negative charge conferred by its highly phosphorylated state, Rap1 maintains interactions with its binding partners. Interestingly, mutations that change the charge of negatively charged residues within the Bqt1-2 binding site of Rap1 abolished the affinity to the Bqt1-2 complex, suggesting that the intrinsic negative charge of Rap1 is crucial for telomere bouquet formation. Conclusions: Whereas Rap1 hyper-phosphorylation observed in meiotic prophase does not have an apparent role in bouquet formation, the intrinsic negative charge of Rap1 is important for forming interactions with its binding partners. Thus, Rap1 is able to retain bouquet formation under heavily phosphorylated status.

• http://www.biomedcentral.com/1741-7007/13/37

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启动夜间休眠的< > > < /聚球藻作为一种积极主动的过程

Background: Most organisms, especially photoautotrophs, alter their behaviours in response to day–night alternations adaptively because of their great reliance on light. Upon light-to-dark transition, dramatic and universal decreases in transcription level of the majority of the genes in the genome of the unicellular cyanobacterium, Synechococcus elongatus PCC 7942 are observed. Because Synechococcus is an obligate photoautotroph, it has been generally assumed that repression of the transcription in the dark (dark repression) would be caused by a nocturnal decrease in photosynthetic activities through the reduced availability of energy (e.g. adenosine triphosphate (ATP)) needed for mRNA synthesis. Results: However, against this general assumption, we obtained evidence that the rapid and dynamic dark repression is an active process. Although the addition of photosynthesis inhibitors to cells exposed to light mimicked transcription profiles in the dark, it did not significantly affect the cellular level of ATP. By contrast, when ATP levels were decreased by the inhibition of both photosynthesis and respiration, the transcriptional repression is attenuated through inhibition of RNA degradation. This observation indicates that Synechococcus actively downregulates genome-wide transcription in the dark. Even though the level of total mRNA dramatically decreased in the dark, Synechococcus cells were still viable, and they do not need de novo transcription for their survival in the dark for at least 48 h. Conclusions: Dark repression appears to enable cells to enter into nocturnal dormancy as a feed-forward process, which would be advantageous for their survival under periodic nocturnal conditions.

• http://www.biomedcentral.com/1741-7007/13/36

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利用共祖基因组措施维护濒危和家养的猪种群多样性和健身[研究]

Conservation and breeding programs aim at maintaining the most diversity, thereby avoiding deleterious effects of inbreeding while maintaining enough variation from which traits of interest can be selected. Theoretically, the most diversity is maintained using optimal contributions based on many markers to calculate coancestries, but this can decrease fitness by maintaining linked deleterious variants. The heterogeneous patterns of coancestry displayed in pigs make them an excellent model to test these predictions. We propose methods to measure coancestry and fitness from resequencing data and use them in population management. We analyzed the resequencing data of Sus cebifrons, a highly endangered porcine species from the Philippines, and genotype data from the Pietrain domestic breed. By analyzing the demographic history of Sus cebifrons, we inferred two past bottlenecks that resulted in some inbreeding load. In Pietrain, we analyzed signatures of selection possibly associated with commercial traits. We also simulated the management of each population to assess the performance of different optimal contribution methods to maintain diversity, fitness, and selection signatures. Maximum genetic diversity was maintained using marker-by-marker coancestry, and least using genealogical coancestry. Using a measure of coancestry based on shared segments of the genome achieved the best results in terms of diversity and fitness. However, this segment-based management eliminated signatures of selection. We demonstrate that maintaining both diversity and fitness depends on the genomic distribution of deleterious variants, which is shaped by demographic and selection histories. Our findings show the importance of genomic and next-generation sequencing information in the optimal design of breeding or conservation programs.

• http://genome.cshlp.org/cgi/reprint/gr.187039.114v1?rss=1

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检验：微生物基因组从单细胞分离，质量评估，和宏基因组[方法]

Large-scale recovery of genomes from isolates, single cells, and metagenomic data has been made possible by advances in computational methods and substantial reductions in sequencing costs. Although this increasing breadth of draft genomes is providing key information regarding the evolutionary and functional diversity of microbial life, it has become impractical to finish all available reference genomes. Making robust biological inferences from draft genomes requires accurate estimates of their completeness and contamination. Current methods for assessing genome quality are ad hoc and generally make use of a limited number of "marker" genes conserved across all bacterial or archaeal genomes. Here we introduce CheckM, an automated method for assessing the quality of a genome using a broader set of marker genes specific to the position of a genome within a reference genome tree and information about the collocation of these genes. We demonstrate the effectiveness of CheckM using synthetic data and a wide range of isolate-, single-cell-, and metagenome-derived genomes. CheckM is shown to provide accurate estimates of genome completeness and contamination and to outperform existing approaches. Using CheckM, we identify a diverse range of errors currently impacting publicly available isolate genomes and demonstrate that genomes obtained from single cells and metagenomic data vary substantially in quality. In order to facilitate the use of draft genomes, we propose an objective measure of genome quality that can be used to select genomes suitable for specific gene- and genome-centric analyses of microbial communities.

• http://genome.cshlp.org/cgi/reprint/gr.186072.114v2?rss=1

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公司：一种改进的基于一种新的高峰采摘方法探索成像质谱数据分析的管道

Motivation: Matrix Assisted Laser Desorption Ionization-Imaging Mass Spectrometry (MALDI-IMS) in "omics" data acquisition generates detailed information about the spatial distribution of molecules in a given biological sample. Various data processing methods have been developed for exploring the resultant high volume data. However, most of these methods process data in the spectral domain and do not make the most of the important spatial information available through this technology. Therefore, we propose a novel streamlined data analysis pipeline specifically developed for MALDI-IMS data utilizing significant spatial information for identifying hidden significant molecular distribution patterns in these complex datasets.

Methods: The proposed unsupervised algorithm uses Sliding Window Normalization (SWN) and a new spatial distribution based peak picking method developed based on Gray level Co-Occurrence (GCO) matrices followed by clustering of biomolecules. We also use gist descriptors and an improved version of GCO matrices to extract features from molecular images and minimum medoid distance to automatically estimate the number of possible groups.

Results: We evaluated our algorithm using a new MALDI-IMS metabolomics dataset of a plant (Eucalypt) leaf. The algorithm revealed hidden significant molecular distribution patterns in the dataset, which the current Component Analysis and Segmentation Map based approaches failed to extract. We further demonstrate the performance of our peak picking method over other traditional approaches by using a publicly available MALDI-IMS proteomics dataset of a rat brain. Although SWN did not show any significant improvement as compared with using no normalization, the visual assessment showed an improvement as compared to using the median normalization.

Availability and implementation: The source code and sample data are freely available at http://exims.sourceforge.net/.

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv356v1?rss=1

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opossom：塑造全基因组表达景观的Bioconductor的高维的R-包

Motivation: Comprehensive analysis of genome-wide molecular data challenges bioinformatics methodology in terms of intuitive visualization with single-sample resolution, biomarker selection, functional information mining and highly granular stratification of sample classes. oposSOM combines those functionalities making use of a comprehensive analysis and visualization strategy based on self-organizing maps (SOM) machine learning which we call ‘high-dimensional data portraying’. The method was successfully applied in a series of studies using mostly transcriptome data but also data of other OMICs realms. oposSOM is now publicly available as Bioconductor R package.

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv342v1?rss=1

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DNA数据爆炸照亮了青铜时代

Population-scale studies suggest that migrants spread steppe language and technology.

• http://feeds.nature.com/~r/nature/rss/current/~3/qzpwl_T7CEc/522140a

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重复性：用小鼠生物库或失去他们

Now that genetic engineering of mice is so easy, centralized repositories are essential, argue Kent Lloyd and colleagues.

• http://feeds.nature.com/~r/nature/rss/current/~3/X9mICMDlzy8/522151a

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人类的进化：古DNA进入语言的争论

Two studies of ancient human DNA reveal expansions of Bronze Age populations that shed light on the long-running debate about the origins and spread of Indo-European languages. See Article p.167 & Letter p.207

• http://feeds.nature.com/~r/nature/rss/current/~3/iXTWc3fohFA/522164a

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逆转录病毒整合进核小体的结构基础

Retroviral integration is catalysed by a tetramer of integrase (IN) assembled on viral DNA ends in a stable complex, known as the intasome. How the intasome interfaces with chromosomal DNA, which exists in the form of nucleosomal arrays, is currently unknown. Here we show that the prototype foamy virus (PFV) intasome is proficient at stable capture of nucleosomes as targets for integration. Single-particle cryo-electron microscopy reveals a multivalent intasome–nucleosome interface involving both gyres of nucleosomal DNA and one H2A–H2B heterodimer. While the histone octamer remains intact, the DNA is lifted from the surface of the H2A–H2B heterodimer to allow integration at strongly preferred superhelix location ±3.5 positions. Amino acid substitutions disrupting these contacts impinge on the ability of the intasome to engage nucleosomes in vitro and redistribute viral integration sites on the genomic scale. Our findings elucidate the molecular basis for nucleosome capture by the viral DNA recombination machinery and the underlying nucleosome plasticity that allows integration.

• http://feeds.nature.com/~r/nature/rss/aop/~3/xdesqAOffqA/nature14495

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超分子组装巩固细菌外膜蛋白周转

Gram-negative bacteria inhabit a broad range of ecological niches. For Escherichia coli, this includes river water as well as humans and animals, where it can be both a commensal and a pathogen. Intricate regulatory mechanisms ensure that bacteria have the right complement of β-barrel outer membrane proteins (OMPs) to enable adaptation to a particular habitat. Yet no mechanism is known for replacing OMPs in the outer membrane, an issue that is further confounded by the lack of an energy source and the high stability and abundance of OMPs. Here we uncover the process underpinning OMP turnover in E. coli and show it to be passive and binary in nature, in which old OMPs are displaced to the poles of growing cells as new OMPs take their place. Using fluorescent colicins as OMP-specific probes, in combination with ensemble and single-molecule fluorescence microscopy in vivo and in vitro, as well as molecular dynamics simulations, we established the mechanism for binary OMP partitioning. OMPs clustered to form ∼0.5-μm diameter islands, where their diffusion is restricted by promiscuous interactions with other OMPs. OMP islands were distributed throughout the cell and contained the Bam complex, which catalyses the insertion of OMPs in the outer membrane. However, OMP biogenesis occurred as a gradient that was highest at mid-cell but largely absent at cell poles. The cumulative effect is to push old OMP islands towards the poles of growing cells, leading to a binary distribution when cells divide. Hence, the outer membrane of a Gram-negative bacterium is a spatially and temporally organized structure, and this organization lies at the heart of how OMPs are turned over in the membrane.

• http://feeds.nature.com/~r/nature/rss/aop/~3/4HuQNC3mowE/nature14461

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全基因组SNP扫描在鹰嘴豆的特质性调节基因位点识别加速

We identified 44844 high-quality SNPs by sequencing 92 diverse chickpea accessions belonging to a seed and pod trait-specific association panel using reference genome- and de novo-based GBS (genotyping-by-sequencing) assays. A GWAS (genome-wide association study) in an association panel of 211, including the 92 sequenced accessions, identified 22 major genomic loci showing significant association (explaining 23–47% phenotypic variation) with pod and seed number/plant and 100-seed weight. Eighteen trait-regulatory major genomic loci underlying 13 robust QTLs were validated and mapped on an intra-specific genetic linkage map by QTL mapping. A combinatorial approach of GWAS, QTL mapping and gene haplotype-specific LD mapping and transcript profiling uncovered one superior haplotype and favourable natural allelic variants in the upstream regulatory region of a CesA-type cellulose synthase (Ca_Kabuli_CesA3) gene regulating high pod and seed number/plant (explaining 47% phenotypic variation) in chickpea. The up-regulation of this superior gene haplotype correlated with increased transcript expression of Ca_Kabuli_CesA3 gene in the pollen and pod of high pod/seed number accession, resulting in higher cellulose accumulation for normal pollen and pollen tube growth. A rapid combinatorial genome-wide SNP genotyping-based approach has potential to dissect complex quantitative agronomic traits and delineate trait-regulatory genomic loci (candidate genes) for genetic enhancement in crop plants, including chickpea.

• http://feeds.nature.com/~r/srep/rss/current/~3/hl7f19tVjsw/srep11166

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泛素特异性蛋白酶14对朊蛋白的降解

Prion diseases are fatal neurodegenerative disorders characterized by the accumulation of prion protein (PrPC). To date, there is no effective treatment for the disease. The accumulated PrP, termed PrPSc, forms amyloid fibrils and could be infectious. It has been suggested that PrPSc is abnormally folded and resistant to proteolytic degradation, and also inhibits proteasomal functions in infected cells, thereby inducing neuronal death. Recent work indicates that the ubiquitin-proteasome system is involved in quality control of PrPC. To reveal the significance of prion protein ubiqitination, we focused on ubiquitin-specific protease 14 (USP14), a deubiqutinating enzyme that catalyzes trimming of polyubiquitin chains and plays a role in regulation of proteasomal processes. Results from the present study showed that treatment with a selective inhibitor of USP14 reduced PrPC, as well as PrPSc, levels in prion-infected neuronal cells. Overexpression of the dominant negative mutant form of USP14 reduced PrPSc, whereas wildtype USP14 increased PrPSc in prion-infected cells. These results suggest that USP14 prevents degradation of both normal and abnormal PrP. Collectively, a better understanding about the regulation of PrPSc clearance caused by USP14 might contribute greatly to the development of therapeutic strategies for prion diseases.

• http://feeds.nature.com/~r/srep/rss/current/~3/xQkuy1wYAIM/srep11028

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在FGF23参与下颌前突突变的鉴定

Mandibular prognathism (MP) is a severe maxillofacial disorder with undetermined genetic background. We collected a Chinese pedigree with MP which involved in 23 living members of 4 generations. Genome-wide linkage analysis were carried out to obtain the information in this family and a new MP-susceptibility locus, 12pter-p12.3 was identified. Whole-exome sequencing identified a novel heterozygous mutation in fibroblast growth factor (FGF) 23 (; p.A12D) which well segregated with MP in this pedigree within the locus. The mutation was also detected in 3 cases out of 65 sporadic MP patients, but not in any of the 342 control subjects. The p.A12D mutation may disrupt signal peptide function and inhibit secretory in FGF23. Furthermore, mutant FGF23 was overexpressed in 293T cells, increased cytoplasmic accumulation was observed compared with the wild type. We have discovered that c.35C>A mutation in FGF23 strongly associated with MP, which expand our understanding of the genetic contribution to MP pathogenesis.

• http://feeds.nature.com/~r/srep/rss/current/~3/epXOLoovy1Y/srep11250

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一个关键的作用βTGF-β1在海马突触可塑性和记忆

Transforming Growth Factor β1 (TGF-β1) is a well-known neuroprotective and neurotrophic factor demonstrated to play a role in synaptic transmission. However, its involvement in physiological mechanisms underlying synaptic plasticity and memory at hippocampal level has not been thoroughly investigated. Here, we examine the role of TGF-β1 in hippocampal long-term potentiation (LTP) and memory in adult wild type mice. Our data provide evidence that administration of exogenous TGF-β1 is able to convert early-phase-LTP into late-phase-LTP. Furthermore, we show that the block of the endogenous TGF-β1 signaling pathway by the specific TGF-β1 inhibitor SB431542, impairs LTP and object recognition memory. The latter impairment was rescued by administration of exogenous TGF-β1, suggesting that endogenously produced TGF-β1 plays a role in physiological mechanisms underlying LTP and memory. Finally, TGF-β1 functional effect correlates with an increased expression of the phosphorylated transcription factor cAMP-Responsive Element Binding protein.

• http://feeds.nature.com/~r/srep/rss/current/~3/m63WQ3rpmQo/srep11252

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在使用转基因家蚕表达绿色荧光蛋白的体内毒性试验的一种无创性的荧光成像

In drug development, the toxicity of candidate chemicals must be carefully examined in an animal model. Here we developed a live imaging technique using silkworms for a noninvasive toxicity test applicable for drug screening. Injection of carbon tetrachloride, a tissue-injuring chemical, into transgenic silkworms expressing green fluorescent protein (GFP) induced leakage of GFP from the tissues into the hemolymph. The leakage of GFP was suppressed by pre-administration of either cimetidine, a cytochrome P450 inhibitor, or N-acetyl cysteine, a free-radical scavenger. The transgenic silkworm was made transparent by feeding a diet containing chemicals that inhibit uric acid deposition in the epithelial cells. In the transparent silkworms, GFP fluorescence in the fat body could be observed from outside the body. Injection of salicylic acid or iron sulfate, tissue-injuring chemicals, into the transparent silkworms decreased the fluorescence intensity of the GFP in the fat body. These findings suggest that the transparent GFP-expressing silkworm model is useful for evaluating the toxicity of chemicals that induce tissue injury.

• http://feeds.nature.com/~r/srep/rss/current/~3/GkJHTMVJup8/srep11180

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肠易激综合征：为展示和生物序列可视化插画

SUMMARY: Biological sequence diagrams are fundamental for visualizing various functional elements in protein or nucleotide sequences that enable a summarization and presentation of existing information as well as means of intuitive new discoveries. Here, we present a software package called Illustrator of Biological Sequences (IBS) that can be used for representing the organization of either protein or nucleotide sequences, in a convenient, efficient and precise manner. Multiple options are provided in IBS, and biological sequences can be manipulated, recolored or rescaled in a user-defined mode. Also, the final representational artwork can be directly exported into a publication-quality figure.

AVAILABILITY AND IMPLEMENTATION: The standalone package of IBS was implemented in JAVA, while the online service was implemented in HTML5 and JavaScript. Both the standalone package and online service are freely available at http://ibs.biocuckoo.org.

CONTACT: xueyu@hust.edu.cn; renjian.sysu@gmail.com

SUPPLEMENTARY INFORMATION: Supplementary data are available at the journal's web site.

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv362v1?rss=1

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