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Sample records for global gene mining

  1. Global gene mining and the pharmaceutical industry

    SciTech Connect

    Knudsen, Lisbeth E.

    2005-09-01

    Worldwide efforts are ongoing in optimizing medical treatment by searching for the right medicine at the right dose for the individual. Metabolism is regulated by polymorphisms, which may be tested by relatively simple SNP analysis, however requiring DNA from the test individuals. Target genes for the efficiency of a given medicine or predisposition of a given disease are also subject to population studies, e.g., in Iceland, Estonia, Sweden, etc. For hypothesis testing and generation, several bio-banks with samples from patients and healthy persons within the pharmaceutical industry have been established during the past 10 years. Thus, more than 100,000 samples are stored in the freezers of either the pharmaceutical companies or their contractual partners at universities and test institutions. Ethical issues related to data protection of the individuals providing samples to bio-banks are several: nature and extent of information prior to consent, coverage of the consent given by the study person, labeling and storage of the sample and data (coded or anonymized). In general, genetic test data, once obtained, are permanent and cannot be changed. The test data may imply information that is not beneficial to the patient and his/her family (e.g., employment opportunities, insurance, etc.). Furthermore, there may be a long latency between the analysis of the genetic test and the clinical expression of the disease and wide differences in the disease patterns. Consequently, information about some genetic test data may stigmatize patients leading to poor quality of life. This has raised the issue of 'genetic exceptionalism' justifying specific regulation of use of genetic information. Discussions on how to handle sampling and data are ongoing within the industry and the regulatory sphere, the European Agency for the Evaluation of Medicinal Products (EMEA) having issued a position paper, the Council for International Organizations of Medical Sciences (CIOMS) having a working

  2. Global gene mining and the pharmaceutical industry.

    PubMed

    Knudsen, Lisbeth E

    2005-09-01

    Worldwide efforts are ongoing in optimizing medical treatment by searching for the right medicine at the right dose for the individual. Metabolism is regulated by polymorphisms, which may be tested by relatively simple SNP analysis, however requiring DNA from the test individuals. Target genes for the efficiency of a given medicine or predisposition of a given disease are also subject to population studies, e.g., in Iceland, Estonia, Sweden, etc. For hypothesis testing and generation, several bio-banks with samples from patients and healthy persons within the pharmaceutical industry have been established during the past 10 years. Thus, more than 100,000 samples are stored in the freezers of either the pharmaceutical companies or their contractual partners at universities and test institutions. Ethical issues related to data protection of the individuals providing samples to bio-banks are several: nature and extent of information prior to consent, coverage of the consent given by the study person, labeling and storage of the sample and data (coded or anonymized). In general, genetic test data, once obtained, are permanent and cannot be changed. The test data may imply information that is not beneficial to the patient and his/her family (e.g., employment opportunities, insurance, etc.). Furthermore, there may be a long latency between the analysis of the genetic test and the clinical expression of the disease and wide differences in the disease patterns. Consequently, information about some genetic test data may stigmatize patients leading to poor quality of life. This has raised the issue of 'genetic exceptionalism' justifying specific regulation of use of genetic information. Discussions on how to handle sampling and data are ongoing within the industry and the regulatory sphere, the European Agency for the Evaluation of Medicinal Products (EMEA) having issued a position paper, the Council for International Organizations of Medical Sciences (CIOMS) having a working

  3. Coal mine methane global review

    SciTech Connect

    2008-07-01

    This is the second edition of the Coal Mine Methane Global Overview, updated in the summer of 2008. This document contains individual, comprehensive profiles that characterize the coal and coal mine methane sectors of 33 countries - 22 methane to market partners and an additional 11 coal-producing nations. The executive summary provides summary tables that include statistics on coal reserves, coal production, methane emissions, and CMM projects activity. An International Coal Mine Methane Projects Database accompanies this overview. It contains more detailed and comprehensive information on over two hundred CMM recovery and utilization projects around the world. Project information in the database is updated regularly. This document will be updated annually. Suggestions for updates and revisions can be submitted to the Administrative Support Group and will be incorporate into the document as appropriate.

  4. Mining biological databases for candidate disease genes

    NASA Astrophysics Data System (ADS)

    Braun, Terry A.; Scheetz, Todd; Webster, Gregg L.; Casavant, Thomas L.

    2001-07-01

    The publicly-funded effort to sequence the complete nucleotide sequence of the human genome, the Human Genome Project (HGP), has currently produced more than 93% of the 3 billion nucleotides of the human genome into a preliminary `draft' format. In addition, several valuable sources of information have been developed as direct and indirect results of the HGP. These include the sequencing of model organisms (rat, mouse, fly, and others), gene discovery projects (ESTs and full-length), and new technologies such as expression analysis and resources (micro-arrays or gene chips). These resources are invaluable for the researchers identifying the functional genes of the genome that transcribe and translate into the transcriptome and proteome, both of which potentially contain orders of magnitude more complexity than the genome itself. Preliminary analyses of this data identified approximately 30,000 - 40,000 human `genes.' However, the bulk of the effort still remains -- to identify the functional and structural elements contained within the transcriptome and proteome, and to associate function in the transcriptome and proteome to genes. A fortuitous consequence of the HGP is the existence of hundreds of databases containing biological information that may contain relevant data pertaining to the identification of disease-causing genes. The task of mining these databases for information on candidate genes is a commercial application of enormous potential. We are developing a system to acquire and mine data from specific databases to aid our efforts to identify disease genes. A high speed cluster of Linux of workstations is used to analyze sequence and perform distributed sequence alignments as part of our data mining and processing. This system has been used to mine GeneMap99 sequences within specific genomic intervals to identify potential candidate disease genes associated with Bardet-Biedle Syndrome (BBS).

  5. Improving mine safety technology and training: establishing US global leadership

    SciTech Connect

    2006-12-15

    In 2006, the USA's record of mine safety was interrupted by fatalities that rocked the industry and caused the National Mining Association and its members to recommit to returning the US underground coal mining industry to a global mine safety leadership role. This report details a comprehensive approach to increase the odds of survival for miners in emergency situations and to create a culture of prevention of accidents. Among its 75 recommendations are a need to improve communications, mine rescue training, and escape and protection of miners. Section headings of the report are: Introduction; Review of mine emergency situations in the past 25 years: identifying and addressing the issues and complexities; Risk-based design and management; Communications technology; Escape and protection strategies; Emergency response and mine rescue procedures; Training for preparedness; Summary of recommendations; and Conclusions. 37 refs., 3 figs., 5 apps.

  6. Mining metagenomes for novel cellulase genes.

    PubMed

    Duan, Cheng-Jie; Feng, Jia-Xun

    2010-12-01

    Cellulases hydrolyze the β-1,4 linkages of cellulose and are widely used in food, brewing and wine, animal feed, textiles and laundry, and pulp and paper industries, especially for hydrolyzing cellulosic materials into sugars, which can be fermented to produce useful products such as ethanol. Metagenomics has become an alternative approach to conventional culture-dependent methods as it allows exhaustive mining of microbial genomes in their natural environments. This review covers the current state of research and challenges in mining novel cellulase genes from the metagenomes of various environments, and discusses the potential biotechnological applications of metagenome-derived cellulases.

  7. Mining Gene Ontology Data with AGENDA

    PubMed Central

    Ovezmyradov, Guvanch; Lu, Qianhao; Göpfert, Martin C.

    2012-01-01

    The Gene Ontology (GO) initiative is a collaborative effort that uses controlled vocabularies for annotating genetic information. We here present AGENDA (Application for mining Gene Ontology Data), a novel web-based tool for accessing the GO database. AGENDA allows the user to simultaneously retrieve and compare gene lists linked to different GO terms in diverse species using batch queries, facilitating comparative approaches to genetic information. The web-based application offers diverse search options and allows the user to bookmark, visualize, and download the results. AGENDA is an open source web-based application that is freely available for non-commercial use at the project homepage. URL: http://sourceforge.net/projects/bioagenda. PMID:22553422

  8. Mining Gene Ontology Data with AGENDA.

    PubMed

    Ovezmyradov, Guvanch; Lu, Qianhao; Göpfert, Martin C

    2012-01-01

    The Gene Ontology (GO) initiative is a collaborative effort that uses controlled vocabularies for annotating genetic information. We here present AGENDA (Application for mining Gene Ontology Data), a novel web-based tool for accessing the GO database. AGENDA allows the user to simultaneously retrieve and compare gene lists linked to different GO terms in diverse species using batch queries, facilitating comparative approaches to genetic information. The web-based application offers diverse search options and allows the user to bookmark, visualize, and download the results. AGENDA is an open source web-based application that is freely available for non-commercial use at the project homepage. URL: http://sourceforge.net/projects/bioagenda. PMID:22553422

  9. Documenting the global impacts of beach sand mining

    NASA Astrophysics Data System (ADS)

    Young, R.; Griffith, A.

    2009-04-01

    For centuries, beach sand has been mined for use as aggregate in concrete, for heavy minerals, and for construction fill. The global extent and impact of this phenomenon has gone relatively unnoticed by academics, NGOs, and major news sources. Most reports of sand mining activities are found at the very local scale (if the mining is ever documented at all). Yet, sand mining in many localities has resulted in the complete destruction of beach (and related) ecosystems along with severe impacts to coastal protection and tourism. The Program for the Study of Developed Shorelines at Western Carolina University and Beachcare.org have initiated the construction of a global database of beach sand mining activities. The database is being built through a combination of site visits and through the data mining of media resources, peer reviewed papers, and reports from private and governmental entities. Currently, we have documented sand mining in 35 countries on 6 continents representing the removal of millions of cubic meters of sand. Problems extend from Asia where critical infrastructure has been disrupted by sand mining to the Caribbean where policy reform has swiftly followed a highly publicized theft of sand. The Program for the Study of Developed Shorelines recently observed extensive sand mining in Morocco at the regional scale. Tens of kilometers of beach have been stripped of sand and the mining continues southward reducing hope of a thriving tourism-based economy. Problems caused by beach sand mining include: destruction of natural beaches and the ecosystems they protect (e.g. dunes, wetlands), habitat loss for globally important species (e.g. turtles, shorebirds), destruction of nearshore marine ecosystems, increased shoreline erosion rates, reduced protection from storms, tsunamis, and wave events, and economic losses through tourist abandonment and loss of coastal aesthetics. The threats posed by sand mining are made even more critical given the prospect of a

  10. Study of global operational needs for mine clearance equipment

    NASA Astrophysics Data System (ADS)

    Blagden, Paddy M.

    2003-09-01

    The Geneva International Centre for Humanitarian Demining studied the needs of landmine clearance groups for equipment to carry out specific functions of mine clearance. This was done on a global level, and useful results were obtained, which will provide the basis for further analysis.

  11. Mining gene expression data by interpreting principal components

    PubMed Central

    Roden, Joseph C; King, Brandon W; Trout, Diane; Mortazavi, Ali; Wold, Barbara J; Hart, Christopher E

    2006-01-01

    Background There are many methods for analyzing microarray data that group together genes having similar patterns of expression over all conditions tested. However, in many instances the biologically important goal is to identify relatively small sets of genes that share coherent expression across only some conditions, rather than all or most conditions as required in traditional clustering; e.g. genes that are highly up-regulated and/or down-regulated similarly across only a subset of conditions. Equally important is the need to learn which conditions are the decisive ones in forming such gene sets of interest, and how they relate to diverse conditional covariates, such as disease diagnosis or prognosis. Results We present a method for automatically identifying such candidate sets of biologically relevant genes using a combination of principal components analysis and information theoretic metrics. To enable easy use of our methods, we have developed a data analysis package that facilitates visualization and subsequent data mining of the independent sources of significant variation present in gene microarray expression datasets (or in any other similarly structured high-dimensional dataset). We applied these tools to two public datasets, and highlight sets of genes most affected by specific subsets of conditions (e.g. tissues, treatments, samples, etc.). Statistically significant associations for highlighted gene sets were shown via global analysis for Gene Ontology term enrichment. Together with covariate associations, the tool provides a basis for building testable hypotheses about the biological or experimental causes of observed variation. Conclusion We provide an unsupervised data mining technique for diverse microarray expression datasets that is distinct from major methods now in routine use. In test uses, this method, based on publicly available gene annotations, appears to identify numerous sets of biologically relevant genes. It has proven especially

  12. High precision global positioning system for mining applications

    SciTech Connect

    O`Grady, M.

    1997-12-01

    The author discusses today`s satellite technology that has lead to the development of a system that will increase safety and production in surface mining. The Department of Defense is maintaining a satellite system made up of 24 NavStar satellites that allow the use of their frequencies to position equipment anywhere on Earth. The previous satellite system was called the Transit system or Sat-Nav. It consisted of low-orbit satellites (not many up there) that ground-based receivers needed three days of logged data to process sub-meter accuracy positions. With the NavStar network of satellites, centimeter accuracy can be achieved within just a few minutes. Changes to the way one used to survey in the mining industry are being replaced with the Global Positioning System. It has proven to be a system that is more accurate and after the typical learning curve that is required by any new system, will lead to higher productivity; hence, financial rewards are in the immediate future.

  13. OntoGene web services for biomedical text mining

    PubMed Central

    2014-01-01

    Text mining services are rapidly becoming a crucial component of various knowledge management pipelines, for example in the process of database curation, or for exploration and enrichment of biomedical data within the pharmaceutical industry. Traditional architectures, based on monolithic applications, do not offer sufficient flexibility for a wide range of use case scenarios, and therefore open architectures, as provided by web services, are attracting increased interest. We present an approach towards providing advanced text mining capabilities through web services, using a recently proposed standard for textual data interchange (BioC). The web services leverage a state-of-the-art platform for text mining (OntoGene) which has been tested in several community-organized evaluation challenges, with top ranked results in several of them. PMID:25472638

  14. Computer aided gene mining for gingerol biosynthesis

    PubMed Central

    James, Priyanka; Baby, Bincy; Charles, SonaSona; Nair, Lekshmysree Saraschandran; Nazeem, Puthiyaveetil Abdulla

    2015-01-01

    Inspite of the large body of genomic data obtained from the transcriptome of Zingiber officinale, very few studies have focused on the identification and characterization of miRNAs in gingerol biosynthesis. Zingiber officinale transcriptome was analyzed using EST dataset (38169 total) deposited in public domains. In this paper computational functional annotation of the available ESTs and identification of genes which play a significant role in gingerol biosynthesis are described. Zingiber officinale transcriptome was analyzed using EST dataset (38169 total) from ncbi. ESTs were clustered and assembled, resulting in 8624 contigs and 8821 singletons. Assembled dataset was then submitted to the EST functional annotation workflow including blast, gene ontology (go) analysis, and pathway enrichment by kyoto encyclopedia of genes and genomes (kegg) and interproscan. The unigene datasets were further exploited to identify simple sequence repeats that enable linkage mapping. A total of 409 simple sequence repeats were identified from the contigs. Furthermore we examined the existence of novel miRNAs from the ESTs in rhizome, root and leaf tissues. EST analysis revealed the presence of single hypothetical miRNA in rhizome tissue. The hypothetical miRNA is warranted to play an important role in controlling genes involved in gingerol biosynthesis and hence demands experimental validation. The assembly and associated information of transcriptome data provides a comprehensive functional and evolutionary characterization of genomics of Zingiber officinale. As an effort to make the genomic and transcriptomic data widely available to the public domain, the results were integrated into a web-based Ginger EST database which is freely accessible at http://www.kaubic.in/gingerest/. PMID:26229293

  15. ESTIMATE OF GLOBAL METHANE EMISSIONS FROM COAL MINES

    EPA Science Inventory

    Country-specific emissions of methane (CH4) from underground coal mines, surface coal mines, and coal crushing and transport operations are estimated for 1989. Emissions for individual countries are estimated by using two sets of regression equations (R2 values range from 0.56 to...

  16. Integrative data-mining tools to link gene and function.

    PubMed

    El Yacoubi, Basma; de Crécy-Lagard, Valérie

    2014-01-01

    Information derived from genomic and post-genomic data can be efficiently used to link gene and function. Several web-based platforms have been developed to mine these types of data by integrating different tools. This method paper is designed to allow the user to navigate these platforms in order to make functional predictions. The main focus is on phylogenetic distribution and physical clustering tools, but other tools such as pathway reconstruction, gene fusions, and analysis of high-throughput experimental data are also surveyed.

  17. Identification of nitrogen-fixing genes and gene clusters from metagenomic library of acid mine drainage.

    PubMed

    Dai, Zhimin; Guo, Xue; Yin, Huaqun; Liang, Yili; Cong, Jing; Liu, Xueduan

    2014-01-01

    Biological nitrogen fixation is an essential function of acid mine drainage (AMD) microbial communities. However, most acidophiles in AMD environments are uncultured microorganisms and little is known about the diversity of nitrogen-fixing genes and structure of nif gene cluster in AMD microbial communities. In this study, we used metagenomic sequencing to isolate nif genes in the AMD microbial community from Dexing Copper Mine, China. Meanwhile, a metagenome microarray containing 7,776 large-insertion fosmids was constructed to screen novel nif gene clusters. Metagenomic analyses revealed that 742 sequences were identified as nif genes including structural subunit genes nifH, nifD, nifK and various additional genes. The AMD community is massively dominated by the genus Acidithiobacillus. However, the phylogenetic diversity of nitrogen-fixing microorganisms is much higher than previously thought in the AMD community. Furthermore, a 32.5-kb genomic sequence harboring nif, fix and associated genes was screened by metagenome microarray. Comparative genome analysis indicated that most nif genes in this cluster are most similar to those of Herbaspirillum seropedicae, but the organization of the nif gene cluster had significant differences from H. seropedicae. Sequence analysis and reverse transcription PCR also suggested that distinct transcription units of nif genes exist in this gene cluster. nifQ gene falls into the same transcription unit with fixABCX genes, which have not been reported in other diazotrophs before. All of these results indicated that more novel diazotrophs survive in the AMD community.

  18. Identification of Nitrogen-Fixing Genes and Gene Clusters from Metagenomic Library of Acid Mine Drainage

    PubMed Central

    Yin, Huaqun; Liang, Yili; Cong, Jing; Liu, Xueduan

    2014-01-01

    Biological nitrogen fixation is an essential function of acid mine drainage (AMD) microbial communities. However, most acidophiles in AMD environments are uncultured microorganisms and little is known about the diversity of nitrogen-fixing genes and structure of nif gene cluster in AMD microbial communities. In this study, we used metagenomic sequencing to isolate nif genes in the AMD microbial community from Dexing Copper Mine, China. Meanwhile, a metagenome microarray containing 7,776 large-insertion fosmids was constructed to screen novel nif gene clusters. Metagenomic analyses revealed that 742 sequences were identified as nif genes including structural subunit genes nifH, nifD, nifK and various additional genes. The AMD community is massively dominated by the genus Acidithiobacillus. However, the phylogenetic diversity of nitrogen-fixing microorganisms is much higher than previously thought in the AMD community. Furthermore, a 32.5-kb genomic sequence harboring nif, fix and associated genes was screened by metagenome microarray. Comparative genome analysis indicated that most nif genes in this cluster are most similar to those of Herbaspirillum seropedicae, but the organization of the nif gene cluster had significant differences from H. seropedicae. Sequence analysis and reverse transcription PCR also suggested that distinct transcription units of nif genes exist in this gene cluster. nifQ gene falls into the same transcription unit with fixABCX genes, which have not been reported in other diazotrophs before. All of these results indicated that more novel diazotrophs survive in the AMD community. PMID:24498417

  19. Beegle: from literature mining to disease-gene discovery.

    PubMed

    ElShal, Sarah; Tranchevent, Léon-Charles; Sifrim, Alejandro; Ardeshirdavani, Amin; Davis, Jesse; Moreau, Yves

    2016-01-29

    Disease-gene identification is a challenging process that has multiple applications within functional genomics and personalized medicine. Typically, this process involves both finding genes known to be associated with the disease (through literature search) and carrying out preliminary experiments or screens (e.g. linkage or association studies, copy number analyses, expression profiling) to determine a set of promising candidates for experimental validation. This requires extensive time and monetary resources. We describe Beegle, an online search and discovery engine that attempts to simplify this process by automating the typical approaches. It starts by mining the literature to quickly extract a set of genes known to be linked with a given query, then it integrates the learning methodology of Endeavour (a gene prioritization tool) to train a genomic model and rank a set of candidate genes to generate novel hypotheses. In a realistic evaluation setup, Beegle has an average recall of 84% in the top 100 returned genes as a search engine, which improves the discovery engine by 12.6% in the top 5% prioritized genes. Beegle is publicly available at http://beegle.esat.kuleuven.be/.

  20. Beegle: from literature mining to disease-gene discovery.

    PubMed

    ElShal, Sarah; Tranchevent, Léon-Charles; Sifrim, Alejandro; Ardeshirdavani, Amin; Davis, Jesse; Moreau, Yves

    2016-01-29

    Disease-gene identification is a challenging process that has multiple applications within functional genomics and personalized medicine. Typically, this process involves both finding genes known to be associated with the disease (through literature search) and carrying out preliminary experiments or screens (e.g. linkage or association studies, copy number analyses, expression profiling) to determine a set of promising candidates for experimental validation. This requires extensive time and monetary resources. We describe Beegle, an online search and discovery engine that attempts to simplify this process by automating the typical approaches. It starts by mining the literature to quickly extract a set of genes known to be linked with a given query, then it integrates the learning methodology of Endeavour (a gene prioritization tool) to train a genomic model and rank a set of candidate genes to generate novel hypotheses. In a realistic evaluation setup, Beegle has an average recall of 84% in the top 100 returned genes as a search engine, which improves the discovery engine by 12.6% in the top 5% prioritized genes. Beegle is publicly available at http://beegle.esat.kuleuven.be/. PMID:26384564

  1. The Determination of Children's Knowledge of Global Lunar Patterns from Online Essays Using Text Mining Analysis

    ERIC Educational Resources Information Center

    Cheon, Jongpil; Lee, Sangno; Smith, Walter; Song, Jaeki; Kim, Yongjin

    2013-01-01

    The purpose of this study was to use text mining analysis of early adolescents' online essays to determine their knowledge of global lunar patterns. Australian and American students in grades five to seven wrote about global lunar patterns they had discovered by sharing observations with each other via the Internet. These essays were analyzed for…

  2. Literature Mining and Ontology based Analysis of Host-Brucella Gene-Gene Interaction Network.

    PubMed

    Karadeniz, İlknur; Hur, Junguk; He, Yongqun; Özgür, Arzucan

    2015-01-01

    Brucella is an intracellular bacterium that causes chronic brucellosis in humans and various mammals. The identification of host-Brucella interaction is crucial to understand host immunity against Brucella infection and Brucella pathogenesis against host immune responses. Most of the information about the inter-species interactions between host and Brucella genes is only available in the text of the scientific publications. Many text-mining systems for extracting gene and protein interactions have been proposed. However, only a few of them have been designed by considering the peculiarities of host-pathogen interactions. In this paper, we used a text mining approach for extracting host-Brucella gene-gene interactions from the abstracts of articles in PubMed. The gene-gene interactions here represent the interactions between genes and/or gene products (e.g., proteins). The SciMiner tool, originally designed for detecting mammalian gene/protein names in text, was extended to identify host and Brucella gene/protein names in the abstracts. Next, sentence-level and abstract-level co-occurrence based approaches, as well as sentence-level machine learning based methods, originally designed for extracting intra-species gene interactions, were utilized to extract the interactions among the identified host and Brucella genes. The extracted interactions were manually evaluated. A total of 46 host-Brucella gene interactions were identified and represented as an interaction network. Twenty four of these interactions were identified from sentence-level processing. Twenty two additional interactions were identified when abstract-level processing was performed. The Interaction Network Ontology (INO) was used to represent the identified interaction types at a hierarchical ontology structure. Ontological modeling of specific gene-gene interactions demonstrates that host-pathogen gene-gene interactions occur at experimental conditions which can be ontologically represented. Our

  3. Applications of soft computing in Mining Undiscovered Global Porphyry Copper Deposits

    NASA Astrophysics Data System (ADS)

    Friedel, M. J.

    2011-12-01

    We demonstrate the efficacy of an unsupervised artificial neural network, called a self-organizing map (SOM), to facilitate modeling of undiscovered porphyry copper deposits at the global scale. Specifically, the SOM can provide relevant model input for quantifying the amounts of undiscovered metals, and predicting the economic feasibility of mining undiscovered deposits. In quantifying the amounts of metals, the SOM is used to estimate missing data values, estimate numbers of deposits, and evaluate grade and tonnage models. In predicting the economic feasibility of mining, the SOM is used to derive empirical equations. Examples are provided including the prediction of economic likelihood for mining a permissive tract in the Yukon Territory, Canada.

  4. Stratification of Gene Coexpression Patterns and GO Function Mining for a RNA-Seq Data Series

    PubMed Central

    Zhao, Hui; Cao, Fenglin; Xu, Huafeng; Fei, Yiping; Wu, Longyue; Ye, Xiangmei; Yang, Dongguang; Liu, Xiuhua; Li, Xia; Zhou, Jin

    2014-01-01

    RNA-Seq is emerging as an increasingly important tool in biological research, and it provides the most direct evidence of the relationship between the physiological state and molecular changes in cells. A large amount of RNA-Seq data across diverse experimental conditions have been generated and deposited in public databases. However, most developed approaches for coexpression analyses focus on the coexpression pattern mining of the transcriptome, thereby ignoring the magnitude of gene differences in one pattern. Furthermore, the functional relationships of genes in one pattern, and notably among patterns, were not always recognized. In this study, we developed an integrated strategy to identify differential coexpression patterns of genes and probed the functional mechanisms of the modules. Two real datasets were used to validate the method and allow comparisons with other methods. One of the datasets was selected to illustrate the flow of a typical analysis. In summary, we present an approach to robustly detect coexpression patterns in transcriptomes and to stratify patterns according to their relative differences. Furthermore, a global relationship between patterns and biological functions was constructed. In addition, a freely accessible web toolkit “coexpression pattern mining and GO functional analysis” (COGO) was developed. PMID:24955372

  5. Carbon Nanomaterials Alter Global Gene Expression Profiles.

    PubMed

    Woodman, Sara; Short, John C W; McDermott, Hyoeun; Linan, Alexander; Bartlett, Katelyn; Gadila, Shiva Kumar Goud; Schmelzle, Katie; Wanekaya, Adam; Kim, Kyoungtae

    2016-05-01

    Carbon nanomaterials (CNMs), which include carbon nanotubes (CNTs) and their derivatives, have diverse technological and biomedical applications. The potential toxicity of CNMs to cells and tissues has become an important emerging question in nanotechnology. To assess the toxicity of CNTs and fullerenol C60(OH)24, we in the present work used the budding yeast Saccharomyces cerevisiae, one of the simplest eukaryotic organisms that share fundamental aspects of eukaryotic cell biology. We found that treatment with CNMs, regardless of their physical shape, negatively affected the growth rates, end-point cell densities and doubling times of CNM-exposed yeast cells when compared to unexposed cells. To investigate potential mechanisms behind the CNMs-induced growth defects, we performed RNA-Seq dependent transcriptional analysis and constructed global gene expression profiles of fullerenol C60(OH)24- and CNT-treated cells. When compared to non-treated control cells, CNM-treated cells displayed differential expression of genes whose functions are implicated in membrane transporters and stress response, although differentially expressed genes were not consistent between CNT- and fullerenol C60(OH)24-treated groups, leading to our conclusion that CNMs could serve as environmental toxic factors to eukaryotic cells. PMID:27483901

  6. Mining Gene Expression Data Focusing Cancer Therapeutics: A Digest.

    PubMed

    Jauhari, Shaurya; Rizvi, S A M

    2014-01-01

    An understanding towards genetics and epigenetics is essential to cope up with the paradigm shift which is underway. Personalized medicine and gene therapy will confluence the days to come. This review highlights traditional approaches as well as current advancements in the analysis of the gene expression data from cancer perspective. Due to improvements in biometric instrumentation and automation, it has become easier to collect a lot of experimental data in molecular biology. Analysis of such data is extremely important as it leads to knowledge discovery that can be validated by experiments. Previously, the diagnosis of complex genetic diseases has conventionally been done based on the non-molecular characteristics like kind of tumor tissue, pathological characteristics, and clinical phase. The microarray data can be well accounted for high dimensional space and noise. Same were the reasons for ineffective and imprecise results. Several machine learning and data mining techniques are presently applied for identifying cancer using gene expression data. While differences in efficiency do exist, none of the well-established approaches is uniformly superior to others. The quality of algorithm is important, but is not in itself a guarantee of the quality of a specific data analysis.

  7. Shift in Global Tantalum Mine Production, 2000–2014

    USGS Publications Warehouse

    Bleiwas, Donald I.; Papp, John F.; Yager, Thomas R.

    2015-12-10

    One of the activities of the U.S. Geological Survey National Minerals Information Center (USGS-NMIC) is to analyze global supply chains and characterize major components of mineral and material flows from ore extraction through processing to first tier products. These analyses support the core mission of the USGS-NMIC as the Federal entity responsible for the collection, analysis, and dissemination of objective, unbiased, factual information on minerals essential to the U.S. economy and national security.

  8. Allele Mining Strategies: Principles and Utilisation for Blast Resistance Genes in Rice (Oryza sativa L.).

    PubMed

    Ashkani, Sadegh; Yusop, Mohd Rafii; Shabanimofrad, Mahmoodreza; Azady, Amin; Ghasemzadeh, Ali; Azizi, Parisa; Latif, Mohammad Abdul

    2015-01-01

    Allele mining is a promising way to dissect naturally occurring allelic variants of candidate genes with essential agronomic qualities. With the identification, isolation and characterisation of blast resistance genes in rice, it is now possible to dissect the actual allelic variants of these genes within an array of rice cultivars via allele mining. Multiple alleles from the complex locus serve as a reservoir of variation to generate functional genes. The routine sequence exchange is one of the main mechanisms of R gene evolution and development. Allele mining for resistance genes can be an important method to identify additional resistance alleles and new haplotypes along with the development of allele-specific markers for use in marker-assisted selection. Allele mining can be visualised as a vital link between effective utilisation of genetic and genomic resources in genomics-driven modern plant breeding. This review studies the actual concepts and potential of mining approaches for the discovery of alleles and their utilisation for blast resistance genes in rice. The details provided here will be important to provide the rice breeder with a worthwhile introduction to allele mining and its methodology for breakthrough discovery of fresh alleles hidden in hereditary diversity, which is vital for crop improvement.

  9. Identification of underground mine workings with the use of global positioning system technology

    SciTech Connect

    Canty, G.A.; Everett, J.W.; Sharp, M.

    1998-12-31

    Identification of underground mine workings for well drilling is a difficult task given the limited resources available and lack of reliable information. Relic mine maps of questionable accuracy and difficulty in correlating the subsurface to the surface, make the process of locating wells arduous. With the development of global positioning system (GPS), specific locations on the earth can be identified with the aid of satellites. This technology can be applied to mine workings identification given a few necessary, precursory details. For an abandoned mine treatment project conducted by the University of Oklahoma, in conjunction with the Oklahoma Conservation Commission, a Trimble ProXL 8 channel GPS receiver was employed to locate specific points on the surface with respect to a mine map. A 1925 mine map was digitized into AutoCAD version 13 software. Surface features identified on the map, such as mine adits, were located and marked in the field using the GPS receiver. These features were than imported into AutoCAD and referenced with the same points drawn on the map. A rubber sheeting program, Multric, was used to tweak the points so the map features correlated with the surface points. The correlation of these features allowed the map to be geo-referenced with the surface. Specific drilling points were located on the digitized map and assigned a latitude and longitude. The GPS receiver, using real time differential correction, was used to locate these points in the field. This method was assumed to be relatively accurate, to within 5 to 15 feet.

  10. Global direct pressures on biodiversity by large-scale metal mining: Spatial distribution and implications for conservation.

    PubMed

    Murguía, Diego I; Bringezu, Stefan; Schaldach, Rüdiger

    2016-09-15

    Biodiversity loss is widely recognized as a serious global environmental change process. While large-scale metal mining activities do not belong to the top drivers of such change, these operations exert or may intensify pressures on biodiversity by adversely changing habitats, directly and indirectly, at local and regional scales. So far, analyses of global spatial dynamics of mining and its burden on biodiversity focused on the overlap between mines and protected areas or areas of high value for conservation. However, it is less clear how operating metal mines are globally exerting pressure on zones of different biodiversity richness; a similar gap exists for unmined but known mineral deposits. By using vascular plants' diversity as a proxy to quantify overall biodiversity, this study provides a first examination of the global spatial distribution of mines and deposits for five key metals across different biodiversity zones. The results indicate that mines and deposits are not randomly distributed, but concentrated within intermediate and high diversity zones, especially bauxite and silver. In contrast, iron, gold, and copper mines and deposits are closer to a more proportional distribution while showing a high concentration in the intermediate biodiversity zone. Considering the five metals together, 63% and 61% of available mines and deposits, respectively, are located in intermediate diversity zones, comprising 52% of the global land terrestrial surface. 23% of mines and 20% of ore deposits are located in areas of high plant diversity, covering 17% of the land. 13% of mines and 19% of deposits are in areas of low plant diversity, comprising 31% of the land surface. Thus, there seems to be potential for opening new mines in areas of low biodiversity in the future. PMID:27262340

  11. The Determination of Children's Knowledge of Global Lunar Patterns from Online Essays Using Text Mining Analysis

    NASA Astrophysics Data System (ADS)

    Cheon, Jongpil; Lee, Sangno; Smith, Walter; Song, Jaeki; Kim, Yongjin

    2013-04-01

    The purpose of this study was to use text mining analysis of early adolescents' online essays to determine their knowledge of global lunar patterns. Australian and American students in grades five to seven wrote about global lunar patterns they had discovered by sharing observations with each other via the Internet. These essays were analyzed for the students' inclusion of words associated with the shape (i.e., phase), orientation and location of the Moon along with words about similarities and differences. Almost all students wrote about shape but fewer wrote about orientation or location. Students infrequently included words about similarities or differences in the same sentence with shape, orientation or location. Similar to studies about children's and adults' lunar misconceptions, it was found that male and female early adolescents also lacked a robust understanding of global lunar patterns.

  12. Global Analysis of Horizontal Gene Transfer in Fusarium verticillioides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The co-occurrence of microbes within plants and other specialized niches may facilitate horizontal gene transfer (HGT) affecting host-pathogen interactions. We recently identified fungal-to-fungal HGTs involving metabolic gene clusters. For a global analysis of HGTs in the maize pathogen Fusarium ve...

  13. Intrinsic limits to gene regulation by global crosstalk

    PubMed Central

    Friedlander, Tamar; Prizak, Roshan; Guet, Călin C.; Barton, Nicholas H.; Tkačik, Gašper

    2016-01-01

    Gene regulation relies on the specificity of transcription factor (TF)–DNA interactions. Limited specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to noncognate TF–DNA interactions or remains erroneously inactive. As each TF can have numerous interactions with noncognate cis-regulatory elements, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyse the effects of global crosstalk on gene regulation. We find that crosstalk presents a significant challenge for organisms with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting at equilibrium, including variants of cooperativity and combinatorial regulation. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements. PMID:27489144

  14. The Ocean as a Global Reservoir of Antibiotic Resistance Genes

    PubMed Central

    Hatosy, Stephen M.

    2015-01-01

    Recent studies of natural environments have revealed vast genetic reservoirs of antibiotic resistance (AR) genes. Soil bacteria and human pathogens share AR genes, and AR genes have been discovered in a variety of habitats. However, there is little knowledge about the presence and diversity of AR genes in marine environments and which organisms host AR genes. To address this, we identified the diversity of genes conferring resistance to ampicillin, tetracycline, nitrofurantoin, and sulfadimethoxine in diverse marine environments using functional metagenomics (the cloning and screening of random DNA fragments). Marine environments were host to a diversity of AR-conferring genes. Antibiotic-resistant clones were found at all sites, with 28% of the genes identified as known AR genes (encoding beta-lactamases, bicyclomycin resistance pumps, etc.). However, the majority of AR genes were not previously classified as such but had products similar to proteins such as transport pumps, oxidoreductases, and hydrolases. Furthermore, 44% of the genes conferring antibiotic resistance were found in abundant marine taxa (e.g., Pelagibacter, Prochlorococcus, and Vibrio). Therefore, we uncovered a previously unknown diversity of genes that conferred an AR phenotype among marine environments, which makes the ocean a global reservoir of both clinically relevant and potentially novel AR genes. PMID:26296734

  15. Global demand for rare earth resources and strategies for green mining.

    PubMed

    Dutta, Tanushree; Kim, Ki-Hyun; Uchimiya, Minori; Kwon, Eilhann E; Jeon, Byong-Hun; Deep, Akash; Yun, Seong-Taek

    2016-10-01

    Rare earth elements (REEs) are essential raw materials for emerging renewable energy resources and 'smart' electronic devices. Global REE demand is slated to grow at an annual rate of 5% by 2020. This high growth rate will require a steady supply base of REEs in the long run. At present, China is responsible for 85% of global rare earth oxide (REO) production. To overcome this monopolistic supply situation, new strategies and investments are necessary to satisfy domestic supply demands. Concurrently, environmental, economic, and social problems arising from REE mining must be addressed. There is an urgent need to develop efficient REE recycling techniques from end-of-life products, technologies to minimize the amount of REEs required per unit device, and methods to recover them from fly ash or fossil fuel-burning wastes. PMID:27295408

  16. Global demand for rare earth resources and strategies for green mining.

    PubMed

    Dutta, Tanushree; Kim, Ki-Hyun; Uchimiya, Minori; Kwon, Eilhann E; Jeon, Byong-Hun; Deep, Akash; Yun, Seong-Taek

    2016-10-01

    Rare earth elements (REEs) are essential raw materials for emerging renewable energy resources and 'smart' electronic devices. Global REE demand is slated to grow at an annual rate of 5% by 2020. This high growth rate will require a steady supply base of REEs in the long run. At present, China is responsible for 85% of global rare earth oxide (REO) production. To overcome this monopolistic supply situation, new strategies and investments are necessary to satisfy domestic supply demands. Concurrently, environmental, economic, and social problems arising from REE mining must be addressed. There is an urgent need to develop efficient REE recycling techniques from end-of-life products, technologies to minimize the amount of REEs required per unit device, and methods to recover them from fly ash or fossil fuel-burning wastes.

  17. Gold Mining in the Peruvian Amazon: Global Prices, Deforestation, and Mercury Imports

    PubMed Central

    Swenson, Jennifer J.; Carter, Catherine E.; Domec, Jean-Christophe; Delgado, Cesar I.

    2011-01-01

    Many factors such as poverty, ineffective institutions and environmental regulations may prevent developing countries from managing how natural resources are extracted to meet a strong market demand. Extraction for some resources has reached such proportions that evidence is measurable from space. We present recent evidence of the global demand for a single commodity and the ecosystem destruction resulting from commodity extraction, recorded by satellites for one of the most biodiverse areas of the world. We find that since 2003, recent mining deforestation in Madre de Dios, Peru is increasing nonlinearly alongside a constant annual rate of increase in international gold price (∼18%/yr). We detect that the new pattern of mining deforestation (1915 ha/year, 2006–2009) is outpacing that of nearby settlement deforestation. We show that gold price is linked with exponential increases in Peruvian national mercury imports over time (R2 = 0.93, p = 0.04, 2003–2009). Given the past rates of increase we predict that mercury imports may more than double for 2011 (∼500 t/year). Virtually all of Peru's mercury imports are used in artisanal gold mining. Much of the mining increase is unregulated/artisanal in nature, lacking environmental impact analysis or miner education. As a result, large quantities of mercury are being released into the atmosphere, sediments and waterways. Other developing countries endowed with gold deposits are likely experiencing similar environmental destruction in response to recent record high gold prices. The increasing availability of satellite imagery ought to evoke further studies linking economic variables with land use and cover changes on the ground. PMID:21526143

  18. Gold mining in the Peruvian Amazon: global prices, deforestation, and mercury imports.

    PubMed

    Swenson, Jennifer J; Carter, Catherine E; Domec, Jean-Christophe; Delgado, Cesar I

    2011-04-19

    Many factors such as poverty, ineffective institutions and environmental regulations may prevent developing countries from managing how natural resources are extracted to meet a strong market demand. Extraction for some resources has reached such proportions that evidence is measurable from space. We present recent evidence of the global demand for a single commodity and the ecosystem destruction resulting from commodity extraction, recorded by satellites for one of the most biodiverse areas of the world. We find that since 2003, recent mining deforestation in Madre de Dios, Peru is increasing nonlinearly alongside a constant annual rate of increase in international gold price (∼18%/yr). We detect that the new pattern of mining deforestation (1915 ha/year, 2006-2009) is outpacing that of nearby settlement deforestation. We show that gold price is linked with exponential increases in Peruvian national mercury imports over time (R(2) = 0.93, p = 0.04, 2003-2009). Given the past rates of increase we predict that mercury imports may more than double for 2011 (∼500 t/year). Virtually all of Peru's mercury imports are used in artisanal gold mining. Much of the mining increase is unregulated/artisanal in nature, lacking environmental impact analysis or miner education. As a result, large quantities of mercury are being released into the atmosphere, sediments and waterways. Other developing countries endowed with gold deposits are likely experiencing similar environmental destruction in response to recent record high gold prices. The increasing availability of satellite imagery ought to evoke further studies linking economic variables with land use and cover changes on the ground.

  19. Gold mining in the Peruvian Amazon: global prices, deforestation, and mercury imports.

    PubMed

    Swenson, Jennifer J; Carter, Catherine E; Domec, Jean-Christophe; Delgado, Cesar I

    2011-01-01

    Many factors such as poverty, ineffective institutions and environmental regulations may prevent developing countries from managing how natural resources are extracted to meet a strong market demand. Extraction for some resources has reached such proportions that evidence is measurable from space. We present recent evidence of the global demand for a single commodity and the ecosystem destruction resulting from commodity extraction, recorded by satellites for one of the most biodiverse areas of the world. We find that since 2003, recent mining deforestation in Madre de Dios, Peru is increasing nonlinearly alongside a constant annual rate of increase in international gold price (∼18%/yr). We detect that the new pattern of mining deforestation (1915 ha/year, 2006-2009) is outpacing that of nearby settlement deforestation. We show that gold price is linked with exponential increases in Peruvian national mercury imports over time (R(2) = 0.93, p = 0.04, 2003-2009). Given the past rates of increase we predict that mercury imports may more than double for 2011 (∼500 t/year). Virtually all of Peru's mercury imports are used in artisanal gold mining. Much of the mining increase is unregulated/artisanal in nature, lacking environmental impact analysis or miner education. As a result, large quantities of mercury are being released into the atmosphere, sediments and waterways. Other developing countries endowed with gold deposits are likely experiencing similar environmental destruction in response to recent record high gold prices. The increasing availability of satellite imagery ought to evoke further studies linking economic variables with land use and cover changes on the ground. PMID:21526143

  20. Biomedical Information Extraction: Mining Disease Associated Genes from Literature

    ERIC Educational Resources Information Center

    Huang, Zhong

    2014-01-01

    Disease associated gene discovery is a critical step to realize the future of personalized medicine. However empirical and clinical validation of disease associated genes are time consuming and expensive. In silico discovery of disease associated genes from literature is therefore becoming the first essential step for biomarker discovery to…

  1. Exploring relationships and mining data with the UCSC Gene Sorter.

    PubMed

    Kent, W J; Hsu, Fan; Karolchik, Donna; Kuhn, Robert M; Clawson, Hiram; Trumbower, Heather; Haussler, David

    2005-05-01

    In parallel with the human genome sequencing and assembly effort, many tools have been developed to examine the structure and function of the human gene set. The University of California Santa Cruz (UCSC) Gene Sorter has been created as a gene-based counterpart to the chromosome-oriented UCSC Genome Browser to facilitate the study of gene function and evolution. This simple, but powerful tool provides a graphical display of related genes that can be sorted and filtered based on a variety of criteria. Genes may be ordered based on such characteristics as expression profiles, proximity in genome, shared Gene Ontology (GO) terms, and protein similarity. The display can be restricted to a gene set meeting a specific set of constraints by filtering on expression levels, gene name or ID, chromosomal position, and so on. The default set of information for each gene entry-gene name, selected expression data, a BLASTP E-value, genomic position, and a description-can be configured to include many other types of data, including expanded expression data, related accession numbers and IDs, orthologs in other species, GO terms, and much more. The Gene Sorter, a CGI-based Web application written in C with a MySQL database, is tightly integrated with the other applications in the UCSC Genome Browser suite. Available on a selected subset of the genome assemblies found in the Genome Browser, it further enhances the usefulness of the UCSC tool set in interactive genomic exploration and analysis.

  2. Survival prediction and gene identification with penalized global AUC maximization.

    PubMed

    Liu, Zhenqiu; Gartenhaus, Ronald B; Chen, Xue-Wen; Howell, Charles D; Tan, Ming

    2009-12-01

    Identifying genes (biomarkers) and predicting the clinical outcomes with censored survival times are important for cancer prognosis and pathogenesis. In this article, we propose a novel method with L(1) penalized global AUC summary maximization (L(1)GAUCS). The L(1)GAUCS method is developed for simultaneous gene (feature) selection and survival prediction. L(1) penalty shrinks coefficients and produces some coefficients that are exactly zero, and therefore selects a small subset of genes (features). It is a well-known fact that many genes are highly correlated in gene expression data and the highly correlated genes may function together. We, therefore, define a correlation measure to identify those genes such that their expression level may be low but they are highly correlated with the downstream highly expressed genes selected with L(1)GAUCS. Partial pathways associated with the correlated genes are identified with DAVID (http://david.abcc.ncifcrf.gov/). Experimental results with chemotherapy and gene expression data demonstrate that the proposed procedures can be used for identifying important genes and pathways that are related to time to death due to cancer and for building a parsimonious model for predicting the survival of future patients. Software is available upon request from the first author.

  3. Global and gene specific DNA methylation changes during zebrafish development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    DNA methylation is dynamic through the life of an organism. In this study, we measured the global and gene specific DNA methylation changes in zebrafish at different developmental stages. We found that the methylation percentage of cytosines was 11.75 ± 0.96% in 3.3 hour post fertilization (hpf) zeb...

  4. Mining gene-centric relationships from literature: the roles of gene mutation and gene expression in supporting drug discovery.

    PubMed

    Tari, Luis; Patel, Jagruti; Küntzer, Jan; Li, Ying; Peng, Zhengwei; Wang, Yuan; Aguiar, Laura; Cai, James

    2014-01-01

    Identifying drug target candidates is an important task for early development throughout the drug discovery process. This process is supported by the development of new high-throughput technologies that enable better understanding of disease mechanism. It becomes critical to facilitate effective analysis of the large amount of biological data. However, with much of the biological knowledge represented in the literature in the form of natural text, analysis and interpretation of high-throughput data has not reached its potential effectiveness. In this paper, we describe our solution in employing text mining as a technique in finding scientific information for target and biomarker discovery from the biomedical literature. Our approach utilises natural language processing techniques to capture linguistic patterns for the extraction of biological knowledge from text. Additionally, we discuss how the extracted knowledge is used for the analysis of biological data such as next-generation sequencing and gene expression data.

  5. Implications for global climate change from microbially-produced acid mine drainage

    NASA Astrophysics Data System (ADS)

    Norlund, K. L.; Hitchcock, A. P.; Warren, L. A.

    2009-05-01

    Microbial catalysis of sulphur cycling in acid mine drainage (AMD) environments is well known but the reaction pathways are poorly characterised. These reaction pathways involve both acid-consuming and acid- generating steps, with important consequences for overall AMD production as well as sulphur and carbon global biogeochemical cycles. Mining-associated sulphuric acid has been implicated in climate change through the weathering of carbonate minerals resulting in the release of 29 Tg C/year as carbon dioxide. Understanding of microbial AMD generation is based predominantly on studies of Acidithiobacillus ferrooxidans despite the knowledge that other environmentally common strains of bacteria are also active sulphur oxidizers and that microbial consortia are likely very important in environmental processes. Using an integrated experimental approach including geochemical experimentation, scanning transmission X-ray microscopy (STXM) and fluorescent in situ hybridization (FISH), we document a novel syntrophic sulphur metabolism involving two common mine bacteria: autotrophic sulphur oxidizing Acidithiobacillus ferrooxidans and heterotrophic Acidiphilium spp. The proposed sulphur geochemistry associated with this bacterial consortium produces 40-90% less acid than expected based on abiotic AMD models, with significant implications for both AMD mitigation and AMD carbon flux modelling. The two bacterial strains are specifically spatially segregated within a macrostructure of extracellular polymeric substance (EPS) that provides the necessary microgeochemical conditions for coupled sulphur oxidation and reduction reactions. STXM results identify multiple sulphur oxidation states associated with the pods, indicating that they are the sites of active sulphur disproportionation and recycling. Recent laboratory experimentation using type culture strains of the bacteria involved in pod-formation suggesting that this phenomenon is likely to be widespread in environments

  6. Mining Gene Regulatory Networks by Neural Modeling of Expression Time-Series.

    PubMed

    Rubiolo, Mariano; Milone, Diego H; Stegmayer, Georgina

    2015-01-01

    Discovering gene regulatory networks from data is one of the most studied topics in recent years. Neural networks can be successfully used to infer an underlying gene network by modeling expression profiles as times series. This work proposes a novel method based on a pool of neural networks for obtaining a gene regulatory network from a gene expression dataset. They are used for modeling each possible interaction between pairs of genes in the dataset, and a set of mining rules is applied to accurately detect the subjacent relations among genes. The results obtained on artificial and real datasets confirm the method effectiveness for discovering regulatory networks from a proper modeling of the temporal dynamics of gene expression profiles.

  7. A high-resolution network model for global gene regulation in Mycobacterium tuberculosis.

    PubMed

    Peterson, Eliza J R; Reiss, David J; Turkarslan, Serdar; Minch, Kyle J; Rustad, Tige; Plaisier, Christopher L; Longabaugh, William J R; Sherman, David R; Baliga, Nitin S

    2014-10-01

    The resilience of Mycobacterium tuberculosis (MTB) is largely due to its ability to effectively counteract and even take advantage of the hostile environments of a host. In order to accelerate the discovery and characterization of these adaptive mechanisms, we have mined a compendium of 2325 publicly available transcriptome profiles of MTB to decipher a predictive, systems-scale gene regulatory network model. The resulting modular organization of 98% of all MTB genes within this regulatory network was rigorously tested using two independently generated datasets: a genome-wide map of 7248 DNA-binding locations for 143 transcription factors (TFs) and global transcriptional consequences of overexpressing 206 TFs. This analysis has discovered specific TFs that mediate conditional co-regulation of genes within 240 modules across 14 distinct environmental contexts. In addition to recapitulating previously characterized regulons, we discovered 454 novel mechanisms for gene regulation during stress, cholesterol utilization and dormancy. Significantly, 183 of these mechanisms act uniquely under conditions experienced during the infection cycle to regulate diverse functions including 23 genes that are essential to host-pathogen interactions. These and other insights underscore the power of a rational, model-driven approach to unearth novel MTB biology that operates under some but not all phases of infection. PMID:25232098

  8. Integrating constitutive gene expression and chemoactivity: mining the NCI60 anticancer screen.

    PubMed

    Covell, David G

    2012-01-01

    Studies into the genetic origins of tumor cell chemoactivity pose significant challenges to bioinformatic mining efforts. Connections between measures of gene expression and chemoactivity have the potential to identify clinical biomarkers of compound response, cellular pathways important to efficacy and potential toxicities; all vital to anticancer drug development. An investigation has been conducted that jointly explores tumor-cell constitutive NCI60 gene expression profiles and small-molecule NCI60 growth inhibition chemoactivity profiles, viewed from novel applications of self-organizing maps (SOMs) and pathway-centric analyses of gene expressions, to identify subsets of over- and under-expressed pathway genes that discriminate chemo-sensitive and chemo-insensitive tumor cell types. Linear Discriminant Analysis (LDA) is used to quantify the accuracy of discriminating genes to predict tumor cell chemoactivity. LDA results find 15% higher prediction accuracies, using ∼30% fewer genes, for pathway-derived discriminating genes when compared to genes derived using conventional gene expression-chemoactivity correlations. The proposed pathway-centric data mining procedure was used to derive discriminating genes for ten well-known compounds. Discriminating genes were further evaluated using gene set enrichment analysis (GSEA) to reveal a cellular genetic landscape, comprised of small numbers of key over and under expressed on- and off-target pathway genes, as important for a compound's tumor cell chemoactivity. Literature-based validations are provided as support for chemo-important pathways derived from this procedure. Qualitatively similar results are found when using gene expression measurements derived from different microarray platforms. The data used in this analysis is available at http://pubchem.ncbi.nlm.nih.gov/andhttp://www.ncbi.nlm.nih.gov/projects/geo (GPL96, GSE32474).

  9. An efficient method for mining cross-timepoint gene regulation sequential patterns from time course gene expression datasets

    PubMed Central

    2013-01-01

    Background Observation of gene expression changes implying gene regulations using a repetitive experiment in time course has become more and more important. However, there is no effective method which can handle such kind of data. For instance, in a clinical/biological progression like inflammatory response or cancer formation, a great number of differentially expressed genes at different time points could be identified through a large-scale microarray approach. For each repetitive experiment with different samples, converting the microarray datasets into transactional databases with significant singleton genes at each time point would allow sequential patterns implying gene regulations to be identified. Although traditional sequential pattern mining methods have been successfully proposed and widely used in different interesting topics, like mining customer purchasing sequences from a transactional database, to our knowledge, the methods are not suitable for such biological dataset because every transaction in the converted database may contain too many items/genes. Results In this paper, we propose a new algorithm called CTGR-Span (Cross-Timepoint Gene Regulation Sequential pattern) to efficiently mine CTGR-SPs (Cross-Timepoint Gene Regulation Sequential Patterns) even on larger datasets where traditional algorithms are infeasible. The CTGR-Span includes several biologically designed parameters based on the characteristics of gene regulation. We perform an optimal parameter tuning process using a GO enrichment analysis to yield CTGR-SPs more meaningful biologically. The proposed method was evaluated with two publicly available human time course microarray datasets and it was shown that it outperformed the traditional methods in terms of execution efficiency. After evaluating with previous literature, the resulting patterns also strongly correlated with the experimental backgrounds of the datasets used in this study. Conclusions We propose an efficient CTGR

  10. Mining gene link information for survival pathway hunting.

    PubMed

    Jing, Gao-Jian; Zhang, Zirui; Wang, Hong-Qiang; Zheng, Hong-Mei

    2015-08-01

    This study proposes a gene link-based method for survival time-related pathway hunting. In this method, the authors incorporate gene link information to estimate how a pathway is associated with cancer patient's survival time. Specifically, a gene link-based Cox proportional hazard model (Link-Cox) is established, in which two linked genes are considered together to represent a link variable and the association of the link with survival time is assessed using Cox proportional hazard model. On the basis of the Link-Cox model, the authors formulate a new statistic for measuring the association of a pathway with survival time of cancer patients, referred to as pathway survival score (PSS), by summarising survival significance over all the gene links in the pathway, and devise a permutation test to test the significance of an observed PSS. To evaluate the proposed method, the authors applied it to simulation data and two publicly available real-world gene expression data sets. Extensive comparisons with previous methods show the effectiveness and efficiency of the proposed method for survival pathway hunting. PMID:26243831

  11. DISEASES: text mining and data integration of disease-gene associations.

    PubMed

    Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi; Binder, Janos X; Jensen, Lars Juhl

    2015-03-01

    Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition of human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should not stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases. The DISEASES resource is accessible through a web interface at http://diseases.jensenlab.org/, where the text-mining software and all associations are also freely available for download.

  12. Mining functional relationships in feature subspaces from gene expression profiles and drug activity profiles.

    PubMed

    Bao, Lei; Guo, Tao; Sun, Zhirong

    2002-04-10

    In an effort to determine putative functional relationships between gene expression patterns and drug activity patterns of 60 human cancer cell lines, a novel method was developed to discover local associations within cell line subsets. The association of drug-gene pairs is an explorative way of discovering gene markers that predict clinical tumor sensitivity to therapy. Nine drug-gene networks were discovered, as well as dozens of gene-gene and drug-drug networks. Three drug-gene networks with well studied members were discussed and the literature shows that hypothetical functional relationships exist. Therefore, this method enables the gathering of new information beyond global associations.

  13. YAGM: a web tool for mining associated genes in yeast based on diverse biological associations

    PubMed Central

    2015-01-01

    Background Investigating association between genes can be used in understanding the relations of genes in biological processes. STRING and GeneMANIA are two well-known web tools which can provide a list of associated genes of a query gene based on diverse biological associations such as co-expression, co-localization, co-citation and so on. However, the transcriptional regulation association and mutant phenotype association have not been used in these two web tools. Since the comprehensive transcription factor (TF)-gene binding data, TF-gene regulation data and mutant phenotype data are available in yeast, we developed a web tool called YAGM (Yeast Associated Genes Miner) which constructed the transcriptional regulation association, mutant phenotype association and five commonly used biological associations to mine a list of associated genes of a query yeast gene. Description In YAGM, we collected seven kinds of datasets including TF-gene binding (TFB) data, TF-gene regulation (TFR) data, mutant phenotype (MP) data, functional annotation (FA) data, physical interaction (PI) data, genetic interaction (GI) data, and literature evidence (LE) data. Then by using the hypergeometric test to calculate the association scores of all gene pairs in yeast, we constructed seven biological associations including two transcriptional regulation associations (TFB association and TFR association), MP association, FA association, PI association, GI association, and LE association. Moreover, the expression profile association from SPELL database was also included in YAGM. When using YAGM, users can input a query gene and choose any possible subsets of the eight biological associations, then a list of associated genes of the query gene will be returned based on the chosen biological associations. Conclusions In this study, we presented the YAGM which provides eight biological associations for mining associated genes of a query gene in yeast. Among the eight biological associations

  14. Global Gene Expression Analysis of Murine Limb Development

    PubMed Central

    Taher, Leila; Collette, Nicole M.; Murugesh, Deepa; Maxwell, Evan; Ovcharenko, Ivan; Loots, Gabriela G.

    2011-01-01

    Detailed information about stage-specific changes in gene expression is crucial for understanding the gene regulatory networks underlying development and the various signal transduction pathways contributing to morphogenesis. Here we describe the global gene expression dynamics during early murine limb development, when cartilage, tendons, muscle, joints, vasculature and nerves are specified and the musculoskeletal system of limbs is established. We used whole-genome microarrays to identify genes with differential expression at 5 stages of limb development (E9.5 to 13.5), during fore- and hind-limb patterning. We found that the onset of limb formation is characterized by an up-regulation of transcription factors, which is followed by a massive activation of genes during E10.5 and E11.5 which levels off at later time points. Among the 3520 genes identified as significantly up-regulated in the limb, we find ∼30% to be novel, dramatically expanding the repertoire of candidate genes likely to function in the limb. Hierarchical and stage-specific clustering identified expression profiles that are likely to correlate with functional programs during limb development and further characterization of these transcripts will provide new insights into specific tissue patterning processes. Here, we provide for the first time a comprehensive analysis of developmentally regulated genes during murine limb development, and provide some novel insights into the expression dynamics governing limb morphogenesis. PMID:22174793

  15. Global gene expression analysis of murine limb development.

    PubMed

    Taher, Leila; Collette, Nicole M; Murugesh, Deepa; Maxwell, Evan; Ovcharenko, Ivan; Loots, Gabriela G

    2011-01-01

    Detailed information about stage-specific changes in gene expression is crucial for understanding the gene regulatory networks underlying development and the various signal transduction pathways contributing to morphogenesis. Here we describe the global gene expression dynamics during early murine limb development, when cartilage, tendons, muscle, joints, vasculature and nerves are specified and the musculoskeletal system of limbs is established. We used whole-genome microarrays to identify genes with differential expression at 5 stages of limb development (E9.5 to 13.5), during fore- and hind-limb patterning. We found that the onset of limb formation is characterized by an up-regulation of transcription factors, which is followed by a massive activation of genes during E10.5 and E11.5 which levels off at later time points. Among the 3520 genes identified as significantly up-regulated in the limb, we find ~30% to be novel, dramatically expanding the repertoire of candidate genes likely to function in the limb. Hierarchical and stage-specific clustering identified expression profiles that are likely to correlate with functional programs during limb development and further characterization of these transcripts will provide new insights into specific tissue patterning processes. Here, we provide for the first time a comprehensive analysis of developmentally regulated genes during murine limb development, and provide some novel insights into the expression dynamics governing limb morphogenesis.

  16. Soil metatranscriptomics for mining eukaryotic heavy metal resistance genes.

    PubMed

    Lehembre, Frédéric; Doillon, Didier; David, Elise; Perrotto, Sandrine; Baude, Jessica; Foulon, Julie; Harfouche, Lamia; Vallon, Laurent; Poulain, Julie; Da Silva, Corinne; Wincker, Patrick; Oger-Desfeux, Christine; Richaud, Pierre; Colpaert, Jan V; Chalot, Michel; Fraissinet-Tachet, Laurence; Blaudez, Damien; Marmeisse, Roland

    2013-10-01

    Heavy metals are pollutants which affect all organisms. Since a small number of eukaryotes have been investigated with respect to metal resistance, we hypothesize that many genes that control this phenomenon remain to be identified. This was tested by screening soil eukaryotic metatranscriptomes which encompass RNA from organisms belonging to the main eukaryotic phyla. Soil-extracted polyadenylated mRNAs were converted into cDNAs and 35 of them were selected for their ability to rescue the metal (Cd or Zn) sensitive phenotype of yeast mutants. Few of the genes belonged to families known to confer metal resistance when overexpressed in yeast. Several of them were homologous to genes that had not been studied in the context of metal resistance. For instance, the BOLA ones, which conferred cross metal (Zn, Co, Cd, Mn) resistance may act by interfering with Fe homeostasis. Other genes, such as those encoding 110- to 130-amino-acid-long, cysteine-rich polypeptides, had no homologues in databases. This study confirms that functional metatranscriptomics represents a powerful approach to address basic biological processes in eukaryotes. The selected genes can be used to probe new pathways involved in metal homeostasis and to manipulate the resistance level of selected organisms.

  17. Study of Lateral Gene Transfer in an Acid Mine Drainage Community Enabled by Comparative Genomics

    NASA Astrophysics Data System (ADS)

    Hugenholtz, P.; Croft, L.; Tyson, G. W.; Baker, B. J.; Detter, C.; Richardson, P. M.; Banfield, J. F.

    2002-12-01

    Lateral gene transfer (LGT) is thought to play a crucial role in the ecology and evolution of prokaryotes. We are investigating the role of LGT in an acid mine drainage community hosted in a pyrite-dominated metal sulfide deposit at the Richmond mine at Iron Mountain, CA. Due to biologically-mediated pyrite dissolution, the prevailing conditions within the mine are extremely low pH (< 1.0), very high ionic concentrations (molar concentrations of iron sulfate and mM concentrations of arsenic, copper and zinc), and moderate to high temperatures (30 to >50 C). These conditions are thought to largely isolate the community from potential external gene donors since naked DNA, phage and prokaryotes native to neutral pH habitats do not persist at pH <1.0 precluding an external influx of genes by transformation, transduction and conjugation, respectively. Microbial communities exist in several distinct habitats within Richmond mine including biofilms (subaqueous slime streamers and subaerial slimes) and cells attached directly to pyrite granules. This, however, belies an unusual simplicity in community composition. All communities investigated to date comprise only a handful of phylogenetically distinct organisms, typically dominated by the iron-oxidizing genera Leptospirillum and Ferroplasma. We have undertaken a community genomics analysis of a subaerial biofilm dominated by a Leptospirillum population to facilitate the study of LGT in this type of environment. The genome of Ferroplasma acidarmanus fer1, a minor component of the target community (but a major component of other Richmond mine communities), has been sequenced. Comparative genome analyses indicate that F. acidarmanus and the ancestor of two acidophilic Thermoplasma species belonging to the Euryarchaeota have traded many genes with phylogenetically remote acidophilic Sulfolobus species (Crenarchaeota). The putatively transferred sets of Sulfolobus genes in Ferroplasma and the Thermoplasma ancestor are distinct

  18. Discovery of functional genes for systemic acquired resistance in Arabidopsis thaliana through integrated data mining.

    PubMed

    Pan, Youlian; Pylatuik, Jeffrey D; Ouyang, Junjun; Famili, A Fazel; Fobert, Pierre R

    2004-12-01

    Various data mining techniques combined with sequence motif information in the promoter region of genes were applied to discover functional genes that are involved in the defense mechanism of systemic acquired resistance (SAR) in Arabidopsis thaliana. A series of K-Means clustering with difference-in-shape as distance measure was initially applied. A stability measure was used to validate this clustering process. A decision tree algorithm with the discover-and-mask technique was used to identify a group of most informative genes. Appearance and abundance of various transcription factor binding sites in the promoter region of the genes were studied. Through the combination of these techniques, we were able to identify 24 candidate genes involved in the SAR defense mechanism. The candidate genes fell into 2 highly resolved categories, each category showing significantly unique profiles of regulatory elements in their promoter regions. This study demonstrates the strength of such integration methods and suggests a broader application of this approach.

  19. DGIdb 2.0: mining clinically relevant drug-gene interactions.

    PubMed

    Wagner, Alex H; Coffman, Adam C; Ainscough, Benjamin J; Spies, Nicholas C; Skidmore, Zachary L; Campbell, Katie M; Krysiak, Kilannin; Pan, Deng; McMichael, Joshua F; Eldred, James M; Walker, Jason R; Wilson, Richard K; Mardis, Elaine R; Griffith, Malachi; Griffith, Obi L

    2016-01-01

    The Drug-Gene Interaction Database (DGIdb, www.dgidb.org) is a web resource that consolidates disparate data sources describing drug-gene interactions and gene druggability. It provides an intuitive graphical user interface and a documented application programming interface (API) for querying these data. DGIdb was assembled through an extensive manual curation effort, reflecting the combined information of twenty-seven sources. For DGIdb 2.0, substantial updates have been made to increase content and improve its usefulness as a resource for mining clinically actionable drug targets. Specifically, nine new sources of drug-gene interactions have been added, including seven resources specifically focused on interactions linked to clinical trials. These additions have more than doubled the overall count of drug-gene interactions. The total number of druggable gene claims has also increased by 30%. Importantly, a majority of the unrestricted, publicly-accessible sources used in DGIdb are now automatically updated on a weekly basis, providing the most current information for these sources. Finally, a new web view and API have been developed to allow searching for interactions by drug identifiers to complement existing gene-based search functionality. With these updates, DGIdb represents a comprehensive and user friendly tool for mining the druggable genome for precision medicine hypothesis generation.

  20. DDMGD: the database of text-mined associations between genes methylated in diseases from different species.

    PubMed

    Bin Raies, Arwa; Mansour, Hicham; Incitti, Roberto; Bajic, Vladimir B

    2015-01-01

    Gathering information about associations between methylated genes and diseases is important for diseases diagnosis and treatment decisions. Recent advancements in epigenetics research allow for large-scale discoveries of associations of genes methylated in diseases in different species. Searching manually for such information is not easy, as it is scattered across a large number of electronic publications and repositories. Therefore, we developed DDMGD database (http://www.cbrc.kaust.edu.sa/ddmgd/) to provide a comprehensive repository of information related to genes methylated in diseases that can be found through text mining. DDMGD's scope is not limited to a particular group of genes, diseases or species. Using the text mining system DEMGD we developed earlier and additional post-processing, we extracted associations of genes methylated in different diseases from PubMed Central articles and PubMed abstracts. The accuracy of extracted associations is 82% as estimated on 2500 hand-curated entries. DDMGD provides a user-friendly interface facilitating retrieval of these associations ranked according to confidence scores. Submission of new associations to DDMGD is provided. A comparison analysis of DDMGD with several other databases focused on genes methylated in diseases shows that DDMGD is comprehensive and includes most of the recent information on genes methylated in diseases.

  1. DGIdb 2.0: mining clinically relevant drug–gene interactions

    PubMed Central

    Wagner, Alex H.; Coffman, Adam C.; Ainscough, Benjamin J.; Spies, Nicholas C.; Skidmore, Zachary L.; Campbell, Katie M.; Krysiak, Kilannin; Pan, Deng; McMichael, Joshua F.; Eldred, James M.; Walker, Jason R.; Wilson, Richard K.; Mardis, Elaine R.; Griffith, Malachi; Griffith, Obi L.

    2016-01-01

    The Drug–Gene Interaction Database (DGIdb, www.dgidb.org) is a web resource that consolidates disparate data sources describing drug–gene interactions and gene druggability. It provides an intuitive graphical user interface and a documented application programming interface (API) for querying these data. DGIdb was assembled through an extensive manual curation effort, reflecting the combined information of twenty-seven sources. For DGIdb 2.0, substantial updates have been made to increase content and improve its usefulness as a resource for mining clinically actionable drug targets. Specifically, nine new sources of drug–gene interactions have been added, including seven resources specifically focused on interactions linked to clinical trials. These additions have more than doubled the overall count of drug–gene interactions. The total number of druggable gene claims has also increased by 30%. Importantly, a majority of the unrestricted, publicly-accessible sources used in DGIdb are now automatically updated on a weekly basis, providing the most current information for these sources. Finally, a new web view and API have been developed to allow searching for interactions by drug identifiers to complement existing gene-based search functionality. With these updates, DGIdb represents a comprehensive and user friendly tool for mining the druggable genome for precision medicine hypothesis generation. PMID:26531824

  2. Literature Mining and Ontology based Analysis of Host-Brucella Gene–Gene Interaction Network

    PubMed Central

    Karadeniz, İlknur; Hur, Junguk; He, Yongqun; Özgür, Arzucan

    2015-01-01

    Brucella is an intracellular bacterium that causes chronic brucellosis in humans and various mammals. The identification of host-Brucella interaction is crucial to understand host immunity against Brucella infection and Brucella pathogenesis against host immune responses. Most of the information about the inter-species interactions between host and Brucella genes is only available in the text of the scientific publications. Many text-mining systems for extracting gene and protein interactions have been proposed. However, only a few of them have been designed by considering the peculiarities of host–pathogen interactions. In this paper, we used a text mining approach for extracting host-Brucella gene–gene interactions from the abstracts of articles in PubMed. The gene–gene interactions here represent the interactions between genes and/or gene products (e.g., proteins). The SciMiner tool, originally designed for detecting mammalian gene/protein names in text, was extended to identify host and Brucella gene/protein names in the abstracts. Next, sentence-level and abstract-level co-occurrence based approaches, as well as sentence-level machine learning based methods, originally designed for extracting intra-species gene interactions, were utilized to extract the interactions among the identified host and Brucella genes. The extracted interactions were manually evaluated. A total of 46 host-Brucella gene interactions were identified and represented as an interaction network. Twenty four of these interactions were identified from sentence-level processing. Twenty two additional interactions were identified when abstract-level processing was performed. The Interaction Network Ontology (INO) was used to represent the identified interaction types at a hierarchical ontology structure. Ontological modeling of specific gene–gene interactions demonstrates that host–pathogen gene–gene interactions occur at experimental conditions which can be ontologically

  3. Ionospheric Signature of Surface Mine Blasts from Global Positioning System Measurements

    NASA Technical Reports Server (NTRS)

    Calais, Eric; Minster, J. Bernard; Hofton, Michelle A.; Hedlin, Michael A. H.

    1998-01-01

    Sources such as atmospheric or buried explosions and shallow earthquakes are known to produce infrasonic pressure waves in the atmosphere. Because of the coupling between neutral particles and electrons at ionospheric altitudes, these acoustic and gravity waves induce variations of the ionospheric electron density. The Global Positioning System (GPS) provides a way of directly measuring the total electron content in the ionosphere and, therefore, of detecting such perturbations in the upper atmosphere. In July and August 1996, three large surface mine blasts (1.5 Kt each) were detonated at the Black Thunder coal mine in eastern Wyoming. As part of a seismic and acoustic monitoring- experiment, we deployed five dual-frequency GPS receivers at distances ranging from 50 to 200 km from the mine and were able to detect the ionospheric perturbation caused by the blasts. The perturbation starts 10 to 15 min after the blast, lasts for about 30 min, and propagates with an apparent horizontal velocity of 1200 meters per second. Its amplitude reaches 3 x 10 (exp 14) el per square meters in the 7-3 min period band, a value close to the ionospheric perturbation caused by the M = 6.7 Northridge earthquake. The small signal-to-noise ratio of the perturbation can be improved by slant-stacking the electron content time-series recorded by the different GPS receivers taking into account the horizontal propagation of the perturbation. The energy of the perturbation is concentrated in the 200 to 300 second period band, a result consistent with previous observations and numerical model predictions. The 300 second band probably corresponds to gravity modes and shorter periods to acoustic modes, respectively. Using a 1-D stratified velocity model of the atmosphere we show that linear acoustic ray tracing fits arrival times at all GPS receivers. We interpret the perturbation as a direct acoustic wave caused by the explosion itself. This study shows that even relatively small subsurface

  4. RESEARCH PAPERS : Ionospheric signature of surface mine blasts from Global Positioning System measurements

    NASA Astrophysics Data System (ADS)

    Calais, Eric; Bernard Minster, J.; Hofton, Michelle; Hedlin, Michael

    1998-01-01

    Sources such as atmospheric or buried explosions and shallow earthquakes are known to produce infrasonic pressure waves in the atmosphere Because of the coupling between neutral particles and electrons at ionospheric altitudes, these acoustic and gravity waves induce variations of the ionospheric electron density. The Global Positioning System (GPS) provides a way of directly measuring the total electron content in the ionosphere and, therefore, of detecting such perturbations in the upper atmosphere. In July and August 1996, three large surface mine blasts (1.5 Kt each) were detonated at the Black Thunder coal mine in eastern Wyoming. As part of a seismic and acoustic monitoring experiment, we deployed five dual-frequency GPS receivers at distances ranging from 50 to 200 km from the mine and were able to detect the ionospheric perturbation caused by the blasts. The perturbation starts 10 to 15 min after the blast, lasts for about 30 min, and propagates with an apparent horizontal velocity of 1200 m s- 1. Its amplitude reaches 3 × 1014 el m- 2 in the 7-3 min period band, a value close to the ionospheric perturbation caused by the M=6.7 Northridge earthquake (Calais & Minster 1995). The small signal-to-noise ratio of the perturbation can be improved by slant-stacking the electron content time-series recorded by the different GPS receivers taking into account the horizontal propagation of the perturbation. The energy of the perturbation is concentrated in the 200 to 300 s period band, a result consistent with previous observations and numerical model predictions. The 300 s band probably corresponds to gravity modes and shorter periods to acoustic modes, respectively. Using a 1-D stratified velocity model of the atmosphere we show that linear acoustic ray tracing fits arrival times at all GPS receivers. We interpret the perturbation as a direct acoustic wave caused by the explosion itself. This study shows that even relatively small subsurface events can produce

  5. Global Patterns of Diversity and Selection in Human Tyrosinase Gene

    PubMed Central

    Hudjashov, Georgi; Villems, Richard; Kivisild, Toomas

    2013-01-01

    Global variation in skin pigmentation is one of the most striking examples of environmental adaptation in humans. More than two hundred loci have been identified as candidate genes in model organisms and a few tens of these have been found to be significantly associated with human skin pigmentation in genome-wide association studies. However, the evolutionary history of different pigmentation genes is rather complex: some loci have been subjected to strong positive selection, while others evolved under the relaxation of functional constraints in low UV environment. Here we report the results of a global study of the human tyrosinase gene, which is one of the key enzymes in melanin production, to assess the role of its variation in the evolution of skin pigmentation differences among human populations. We observe a higher rate of non-synonymous polymorphisms in the European sample consistent with the relaxation of selective constraints. A similar pattern was previously observed in the MC1R gene and concurs with UV radiation-driven model of skin color evolution by which mutations leading to lower melanin levels and decreased photoprotection are subject to purifying selection at low latitudes while being tolerated or even favored at higher latitudes because they facilitate UV-dependent vitamin D production. Our coalescent date estimates suggest that the non-synonymous variants, which are frequent in Europe and North Africa, are recent and have emerged after the separation of East and West Eurasian populations. PMID:24040225

  6. Discovery of Phytophthora infestans Genes Expressed in Planta through Mining of cDNA Libraries

    PubMed Central

    Chaves, Diego; Pinzón, Andrés; Grajales, Alejandro; Rojas, Alejandro; Mutis, Gabriel; Cárdenas, Martha; Burbano, Daniel; Jiménez, Pedro; Bernal, Adriana; Restrepo, Silvia

    2010-01-01

    Background Phytophthora infestans (Mont.) de Bary causes late blight of potato and tomato, and has a broad host range within the Solanaceae family. Most studies of the Phytophthora – Solanum pathosystem have focused on gene expression in the host and have not analyzed pathogen gene expression in planta. Methodology/Principal Findings We describe in detail an in silico approach to mine ESTs from inoculated host plants deposited in a database in order to identify particular pathogen sequences associated with disease. We identified candidate effector genes through mining of 22,795 ESTs corresponding to P. infestans cDNA libraries in compatible and incompatible interactions with hosts from the Solanaceae family. Conclusions/Significance We annotated genes of P. infestans expressed in planta associated with late blight using different approaches and assigned putative functions to 373 out of the 501 sequences found in the P. infestans genome draft, including putative secreted proteins, domains associated with pathogenicity and poorly characterized proteins ideal for further experimental studies. Our study provides a methodology for analyzing cDNA libraries and provides an understanding of the plant – oomycete pathosystems that is independent of the host, condition, or type of sample by identifying genes of the pathogen expressed in planta. PMID:20352100

  7. An effective data mining technique for reconstructing gene regulatory networks from time series expression data.

    PubMed

    Ma, Patrick C H; Chan, Keith C C

    2007-06-01

    Recent development in DNA microarray technologies has made the reconstruction of gene regulatory networks (GRNs) feasible. To infer the overall structure of a GRN, there is a need to find out how the expression of each gene can be affected by the others. Many existing approaches to reconstructing GRNs are developed to generate hypotheses about the presence or absence of interactions between genes so that laboratory experiments can be performed afterwards for verification. Since, they are not intended to be used to predict if a gene in an unseen sample has any interactions with other genes, statistical verification of the reliability of the discovered interactions can be difficult. Furthermore, since the temporal ordering of the data is not taken into consideration, the directionality of regulation cannot be established using these existing techniques. To tackle these problems, we propose a data mining technique here. This technique makes use of a probabilistic inference approach to uncover interesting dependency relationships in noisy, high-dimensional time series expression data. It is not only able to determine if a gene is dependent on another but also whether or not it is activated or inhibited. In addition, it can predict how a gene would be affected by other genes even in unseen samples. For performance evaluation, the proposed technique has been tested with real expression data. Experimental results show that it can be very effective. The discovered dependency relationships can reveal gene regulatory relationships that could be used to infer the structures of GRNs.

  8. Hybrid coexpression link similarity graph clustering for mining biological modules from multiple gene expression datasets

    PubMed Central

    2014-01-01

    Background Advances in genomic technologies have enabled the accumulation of vast amount of genomic data, including gene expression data for multiple species under various biological and environmental conditions. Integration of these gene expression datasets is a promising strategy to alleviate the challenges of protein functional annotation and biological module discovery based on a single gene expression data, which suffers from spurious coexpression. Results We propose a joint mining algorithm that constructs a weighted hybrid similarity graph whose nodes are the coexpression links. The weight of an edge between two coexpression links in this hybrid graph is a linear combination of the topological similarities and co-appearance similarities of the corresponding two coexpression links. Clustering the weighted hybrid similarity graph yields recurrent coexpression link clusters (modules). Experimental results on Human gene expression datasets show that the reported modules are functionally homogeneous as evident by their enrichment with biological process GO terms and KEGG pathways. PMID:25221624

  9. MARQ: an online tool to mine GEO for experiments with similar or opposite gene expression signatures.

    PubMed

    Vazquez, Miguel; Nogales-Cadenas, Ruben; Arroyo, Javier; Botías, Pedro; García, Raul; Carazo, Jose M; Tirado, Francisco; Pascual-Montano, Alberto; Carmona-Saez, Pedro

    2010-07-01

    The enormous amount of data available in public gene expression repositories such as Gene Expression Omnibus (GEO) offers an inestimable resource to explore gene expression programs across several organisms and conditions. This information can be used to discover experiments that induce similar or opposite gene expression patterns to a given query, which in turn may lead to the discovery of new relationships among diseases, drugs or pathways, as well as the generation of new hypotheses. In this work, we present MARQ, a web-based application that allows researchers to compare a query set of genes, e.g. a set of over- and under-expressed genes, against a signature database built from GEO datasets for different organisms and platforms. MARQ offers an easy-to-use and integrated environment to mine GEO, in order to identify conditions that induce similar or opposite gene expression patterns to a given experimental condition. MARQ also includes additional functionalities for the exploration of the results, including a meta-analysis pipeline to find genes that are differentially expressed across different experiments. The application is freely available at http://marq.dacya.ucm.es.

  10. Mining the transcriptomes of four commercially important shellfish species for single nucleotide polymorphisms within biomineralization genes.

    PubMed

    Vendrami, David L J; Shah, Abhijeet; Telesca, Luca; Hoffman, Joseph I

    2016-06-01

    Transcriptional profiling not only provides insights into patterns of gene expression, but also generates sequences that can be mined for molecular markers, which in turn can be used for population genetic studies. As part of a large-scale effort to better understand how commercially important European shellfish species may respond to ocean acidification, we therefore mined the transcriptomes of four species (the Pacific oyster Crassostrea gigas, the blue mussel Mytilus edulis, the great scallop Pecten maximus and the blunt gaper Mya truncata) for single nucleotide polymorphisms (SNPs). Illumina data for C. gigas, M. edulis and P. maximus and 454 data for M. truncata were interrogated using GATK and SWAP454 respectively to identify between 8267 and 47,159 high quality SNPs per species (total=121,053 SNPs residing within 34,716 different contigs). We then annotated the transcripts containing SNPs to reveal homology to diverse genes. Finally, as oceanic pH affects the ability of organisms to incorporate calcium carbonate, we honed in on genes implicated in the biomineralization process to identify a total of 1899 SNPs in 157 genes. These provide good candidates for biomarkers with which to study patterns of selection in natural or experimental populations.

  11. Regulation of global gene expression and cell proliferation by APP

    PubMed Central

    Wu, Yili; Zhang, Si; Xu, Qin; Zou, Haiyan; Zhou, Weihui; Cai, Fang; Li, Tingyu; Song, Weihong

    2016-01-01

    Down syndrome (DS), caused by trisomy of chromosome 21, is one of the most common genetic disorders. Patients with DS display growth retardation and inevitably develop characteristic Alzheimer’s disease (AD) neuropathology, including neurofibrillary tangles and neuritic plaques. The expression of amyloid precursor protein (APP) is increased in both DS and AD patients. To reveal the function of APP and elucidate the pathogenic role of increased APP expression in DS and AD, we performed gene expression profiling using microarray method in human cells overexpressing APP. A set of genes are significantly altered, which are involved in cell cycle, cell proliferation and p53 signaling. We found that overexpression of APP inhibits cell proliferation. Furthermore, we confirmed that the downregulation of two validated genes, PSMA5 and PSMB7, inhibits cell proliferation, suggesting that the downregulation of PSMA5 and PSMB7 is involved in APP-induced cell proliferation impairment. Taken together, this study suggests that APP regulates global gene expression and increased APP expression inhibits cell proliferation. Our study provides a novel insight that APP overexpression may contribute to the growth impairment in DS patients and promote AD pathogenesis by inhibiting cell proliferation including neural stem cell proliferation and neurogenesis. PMID:26936520

  12. Corticosteroid-regulated genes in rat kidney: mining time series array data.

    PubMed

    Almon, Richard R; Lai, William; DuBois, Debra C; Jusko, William J

    2005-11-01

    Kidney is a major target for adverse effects associated with corticosteroids. A microarray dataset was generated to examine changes in gene expression in rat kidney in response to methylprednisolone. Four control and 48 drug-treated animals were killed at 16 times after drug administration. Kidney RNA was used to query 52 individual Affymetrix chips, generating data for 15,967 different probe sets for each chip. Mining techniques applicable to time series data that identify drug-regulated changes in gene expression were applied. Four sequential filters eliminated probe sets that were not expressed in the tissue, not regulated by drug, or did not meet defined quality control standards. These filters eliminated 14,890 probe sets (94%) from further consideration. Application of judiciously chosen filters is an effective tool for data mining of time series datasets. The remaining data can then be further analyzed by clustering and mathematical modeling. Initial analysis of this filtered dataset identified a group of genes whose pattern of regulation was highly correlated with prototype corticosteroid enhanced genes. Twenty genes in this group, as well as selected genes exhibiting either downregulation or no regulation, were analyzed for 5' GRE half-sites conserved across species. In general, the results support the hypothesis that the existence of conserved DNA binding sites can serve as an important adjunct to purely analytic approaches to clustering genes into groups with common mechanisms of regulation. This dataset, as well as similar datasets on liver and muscle, are available online in a format amenable to further analysis by others.

  13. Sequential patterns mining and gene sequence visualization to discover novelty from microarray data.

    PubMed

    Sallaberry, A; Pecheur, N; Bringay, S; Roche, M; Teisseire, M

    2011-10-01

    Data mining allow users to discover novelty in huge amounts of data. Frequent pattern methods have proved to be efficient, but the extracted patterns are often too numerous and thus difficult to analyze by end users. In this paper, we focus on sequential pattern mining and propose a new visualization system to help end users analyze the extracted knowledge and to highlight novelty according to databases of referenced biological documents. Our system is based on three visualization techniques: clouds, solar systems, and treemaps. We show that these techniques are very helpful for identifying associations and hierarchical relationships between patterns among related documents. Sequential patterns extracted from gene data using our system were successfully evaluated by two biology laboratories working on Alzheimer's disease and cancer.

  14. Mining expressed sequence tag (EST) libraries for cancer-associated genes.

    PubMed

    Schmitt, Armin O

    2010-01-01

    Originally established in the beginning of the 1990s as a direct route to gene finding, expressed sequence tags (ESTs) still lend themselves as a means to analyze gene expression in almost all human tissues. The type of questions that can be addressed using public EST libraries ranges from tissue-specific gene profiling to the comparison between tissues in diseased and healthy states. Thanks to a multitude of web-based online bioinformatics resources, mining in EST libraries is not restricted to experts in the field of data analysis, but can readily be performed by the medical or life scientist. In this chapter, a couple of cases studies are presented that guide the scientist to the most useful online resources so that they can conduct their own research.

  15. Topological origin of global attractors in gene regulatory networks

    NASA Astrophysics Data System (ADS)

    Zhang, YunJun; Ouyang, Qi; Geng, Zhi

    2015-02-01

    Fixed-point attractors with global stability manifest themselves in a number of gene regulatory networks. This property indicates the stability of regulatory networks against small state perturbations and is closely related to other complex dynamics. In this paper, we aim to reveal the core modules in regulatory networks that determine their global attractors and the relationship between these core modules and other motifs. This work has been done via three steps. Firstly, inspired by the signal transmission in the regulation process, we extract the model of chain-like network from regulation networks. We propose a module of "ideal transmission chain (ITC)", which is proved sufficient and necessary (under certain condition) to form a global fixed-point in the context of chain-like network. Secondly, by examining two well-studied regulatory networks (i.e., the cell-cycle regulatory networks of Budding yeast and Fission yeast), we identify the ideal modules in true regulation networks and demonstrate that the modules have a superior contribution to network stability (quantified by the relative size of the biggest attraction basin). Thirdly, in these two regulation networks, we find that the double negative feedback loops, which are the key motifs of forming bistability in regulation, are connected to these core modules with high network stability. These results have shed new light on the connection between the topological feature and the dynamic property of regulatory networks.

  16. Data Mining for Global Change: A Vision for "Big Data" in the Earth Sciences

    NASA Astrophysics Data System (ADS)

    Steinhaeuser, K.

    2012-12-01

    Over the past several decades, the Earth sciences have undergone a rapid transformation from a historically data-poor to a relatively data-rich environment. This development is largely due to significant improvements in observation technologies (notably satellites since the 1970s) on one hand, and advances in computational tools (both hardware and software) on the other. As a result the Earth sciences are primed to enter the Fourth Paradigm, a term coined by the late Jim Gray to describe a new realm of scientific discovery driven by data analysis - the other three being theory, experimentation, and computer simulation. In particular, observations from remote sensors on satellites and weather radars, in situ sensors and sensor networks, along with outputs of global climate or Earth system models from large-scale simulations as well as regional modeling studies, produce data approaching the Tera- and Petabyte scales. These massive and information-rich datasets offer a significant opportunity for advancing our understanding of the global climate system and in turn our ability to make better informed projections of future climate change, yet current data analysis techniques are not able to realize their full potential. We will outline a vision for the application of "Big Data" tools and technologies in the Earth sciences, which have the potential to make a transformative impact on the toolbox available to the scientist as well as the way science is conducted. For instance, data mining and machine learning could provide novel computational tools that empower scientists to perform analyses more efficiently and effectively than ever before: tedious routine tasks become automated, existing methods scale to significantly larger datasets, and innovative methods may provide new capabilities altogether. Most notably we are not interested in leveraging computation for simulations of increasing scale or resolution but rather in the analysis of datasets of increasing size and

  17. Distributed Function Mining for Gene Expression Programming Based on Fast Reduction.

    PubMed

    Deng, Song; Yue, Dong; Yang, Le-chan; Fu, Xiong; Feng, Ya-zhou

    2016-01-01

    For high-dimensional and massive data sets, traditional centralized gene expression programming (GEP) or improved algorithms lead to increased run-time and decreased prediction accuracy. To solve this problem, this paper proposes a new improved algorithm called distributed function mining for gene expression programming based on fast reduction (DFMGEP-FR). In DFMGEP-FR, fast attribution reduction in binary search algorithms (FAR-BSA) is proposed to quickly find the optimal attribution set, and the function consistency replacement algorithm is given to solve integration of the local function model. Thorough comparative experiments for DFMGEP-FR, centralized GEP and the parallel gene expression programming algorithm based on simulated annealing (parallel GEPSA) are included in this paper. For the waveform, mushroom, connect-4 and musk datasets, the comparative results show that the average time-consumption of DFMGEP-FR drops by 89.09%%, 88.85%, 85.79% and 93.06%, respectively, in contrast to centralized GEP and by 12.5%, 8.42%, 9.62% and 13.75%, respectively, compared with parallel GEPSA. Six well-studied UCI test data sets demonstrate the efficiency and capability of our proposed DFMGEP-FR algorithm for distributed function mining. PMID:26751200

  18. Distributed Function Mining for Gene Expression Programming Based on Fast Reduction.

    PubMed

    Deng, Song; Yue, Dong; Yang, Le-chan; Fu, Xiong; Feng, Ya-zhou

    2016-01-01

    For high-dimensional and massive data sets, traditional centralized gene expression programming (GEP) or improved algorithms lead to increased run-time and decreased prediction accuracy. To solve this problem, this paper proposes a new improved algorithm called distributed function mining for gene expression programming based on fast reduction (DFMGEP-FR). In DFMGEP-FR, fast attribution reduction in binary search algorithms (FAR-BSA) is proposed to quickly find the optimal attribution set, and the function consistency replacement algorithm is given to solve integration of the local function model. Thorough comparative experiments for DFMGEP-FR, centralized GEP and the parallel gene expression programming algorithm based on simulated annealing (parallel GEPSA) are included in this paper. For the waveform, mushroom, connect-4 and musk datasets, the comparative results show that the average time-consumption of DFMGEP-FR drops by 89.09%%, 88.85%, 85.79% and 93.06%, respectively, in contrast to centralized GEP and by 12.5%, 8.42%, 9.62% and 13.75%, respectively, compared with parallel GEPSA. Six well-studied UCI test data sets demonstrate the efficiency and capability of our proposed DFMGEP-FR algorithm for distributed function mining.

  19. Distributed Function Mining for Gene Expression Programming Based on Fast Reduction

    PubMed Central

    Deng, Song; Yue, Dong; Yang, Le-chan; Fu, Xiong; Feng, Ya-zhou

    2016-01-01

    For high-dimensional and massive data sets, traditional centralized gene expression programming (GEP) or improved algorithms lead to increased run-time and decreased prediction accuracy. To solve this problem, this paper proposes a new improved algorithm called distributed function mining for gene expression programming based on fast reduction (DFMGEP-FR). In DFMGEP-FR, fast attribution reduction in binary search algorithms (FAR-BSA) is proposed to quickly find the optimal attribution set, and the function consistency replacement algorithm is given to solve integration of the local function model. Thorough comparative experiments for DFMGEP-FR, centralized GEP and the parallel gene expression programming algorithm based on simulated annealing (parallel GEPSA) are included in this paper. For the waveform, mushroom, connect-4 and musk datasets, the comparative results show that the average time-consumption of DFMGEP-FR drops by 89.09%%, 88.85%, 85.79% and 93.06%, respectively, in contrast to centralized GEP and by 12.5%, 8.42%, 9.62% and 13.75%, respectively, compared with parallel GEPSA. Six well-studied UCI test data sets demonstrate the efficiency and capability of our proposed DFMGEP-FR algorithm for distributed function mining. PMID:26751200

  20. Stress-Survival Gene Identification From an Acid Mine Drainage Algal Mat Community

    NASA Astrophysics Data System (ADS)

    Urbina-Navarrete, J.; Fujishima, K.; Paulino-Lima, I. G.; Rothschild-Mancinelli, B.; Rothschild, L. J.

    2014-12-01

    Microbial communities from acid mine drainage environments are exposed to multiple stressors to include low pH, high dissolved metal loads, seasonal freezing, and desiccation. The microbial and algal communities that inhabit these niche environments have evolved strategies that allow for their ecological success. Metagenomic analyses are useful in identifying species diversity, however they do not elucidate the mechanisms that allow for the resilience of a community under these extreme conditions. Many known or predicted genes encode for protein products that are unknown, or similarly, many proteins cannot be traced to their gene of origin. This investigation seeks to identify genes that are active in an algal consortium during stress from living in an acid mine drainage environment. Our approach involves using the entire community transcriptome for a functional screen in an Escherichia coli host. This approach directly targets the genes involved in survival, without need for characterizing the members of the consortium.The consortium was harvested and stressed with conditions similar to the native environment it was collected from. Exposure to low pH (< 3.2), high metal load, desiccation, and deep freeze resulted in the expression of stress-induced genes that were transcribed into messenger RNA (mRNA). These mRNA transcripts were harvested to build complementary DNA (cDNA) libraries in E. coli. The transformed E. coli were exposed to the same stressors as the original algal consortium to select for surviving cells. Successful cells incorporated the transcripts that encode survival mechanisms, thus allowing for selection and identification of the gene(s) involved. Initial selection screens for freeze and desiccation tolerance have yielded E. coli that are 1 order of magnitude more resistant to freezing (0.01% survival of control with no transcript, 0.2% survival of E. coli with transcript) and 3 orders of magnitude more resistant to desiccation (0.005% survival of

  1. Mining royalties: a global study of their impact on investors, government and civil society

    SciTech Connect

    Otto James

    2006-08-15

    The book discusses the history of royalties and the types currently in use, covering issues such as tax administration, revenue distribution and reporting. It identifies the strengths and weaknesses of various royalty approaches and their impact on production decisions and mine economics. A section on governance looks at the management of mining revenue by governments and the need for transparency. There is an attached CD with 4 appendixes with examples of royalty legislation from over 40 countries. 10 figs., 40 tabs., 4 apps.

  2. Bioactivity-guided genome mining reveals the lomaiviticin biosynthetic gene cluster in Salinispora tropica.

    PubMed

    Kersten, Roland D; Lane, Amy L; Nett, Markus; Richter, Taylor K S; Duggan, Brendan M; Dorrestein, Pieter C; Moore, Bradley S

    2013-05-27

    The use of genome sequences has become routine in guiding the discovery and identification of microbial natural products and their biosynthetic pathways. In silico prediction of molecular features, such as metabolic building blocks, physico-chemical properties or biological functions, from orphan gene clusters has opened up the characterization of many new chemo- and genotypes in genome mining approaches. Here, we guided our genome mining of two predicted enediyne pathways in Salinispora tropica CNB-440 by a DNA interference bioassay to isolate DNA-targeting enediyne polyketides. An organic extract of S. tropica showed DNA-interference activity that surprisingly was not abolished in genetic mutants of the targeted enediyne pathways, ST_pks1 and spo. Instead we showed that the product of the orphan type II polyketide synthase pathway, ST_pks2, is solely responsible for the DNA-interfering activity of the parent strain. Subsequent comparative metabolic profiling revealed the lomaiviticins, glycosylated diazofluorene polyketides, as the ST_pks2 products. This study marks the first report of the 59 open reading frame lomaiviticin gene cluster (lom) and supports the biochemical logic of their dimeric construction through a pathway related to the kinamycin monomer.

  3. Independent component analysis: mining microarray data for fundamental human gene expression modules.

    PubMed

    Engreitz, Jesse M; Daigle, Bernie J; Marshall, Jonathan J; Altman, Russ B

    2010-12-01

    As public microarray repositories rapidly accumulate gene expression data, these resources contain increasingly valuable information about cellular processes in human biology. This presents a unique opportunity for intelligent data mining methods to extract information about the transcriptional modules underlying these biological processes. Modeling cellular gene expression as a combination of functional modules, we use independent component analysis (ICA) to derive 423 fundamental components of human biology from a 9395-array compendium of heterogeneous expression data. Annotation using the Gene Ontology (GO) suggests that while some of these components represent known biological modules, others may describe biology not well characterized by existing manually-curated ontologies. In order to understand the biological functions represented by these modules, we investigate the mechanism of the preclinical anti-cancer drug parthenolide (PTL) by analyzing the differential expression of our fundamental components. Our method correctly identifies known pathways and predicts that N-glycan biosynthesis and T-cell receptor signaling may contribute to PTL response. The fundamental gene modules we describe have the potential to provide pathway-level insight into new gene expression datasets.

  4. Differential global gene expression in red and white skeletal muscle

    NASA Technical Reports Server (NTRS)

    Campbell, W. G.; Gordon, S. E.; Carlson, C. J.; Pattison, J. S.; Hamilton, M. T.; Booth, F. W.

    2001-01-01

    The differences in gene expression among the fiber types of skeletal muscle have long fascinated scientists, but for the most part, previous experiments have only reported differences of one or two genes at a time. The evolving technology of global mRNA expression analysis was employed to determine the potential differential expression of approximately 3,000 mRNAs between the white quad (white muscle) and the red soleus muscle (mixed red muscle) of female ICR mice (30-35 g). Microarray analysis identified 49 mRNA sequences that were differentially expressed between white and mixed red skeletal muscle, including newly identified differential expressions between muscle types. For example, the current findings increase the number of known, differentially expressed mRNAs for transcription factors/coregulators by nine and signaling proteins by three. The expanding knowledge of the diversity of mRNA expression between white and mixed red muscle suggests that there could be quite a complex regulation of phenotype between muscles of different fiber types.

  5. Global gene expression response to telomerase in bovine adrenocortical cells

    SciTech Connect

    Perrault, Steven D.; Hornsby, Peter J.; Betts, Dean H. . E-mail: bettsd@uoguelph.ca

    2005-09-30

    The infinite proliferative capability of most immortalized cells is dependent upon the presence of the enzyme telomerase and its ability to maintain telomere length and structure. However, telomerase may be involved in a greater system than telomere length regulation, as recent evidence has shown it capable of increasing wound healing in vivo, and improving cellular proliferation rate and survival from apoptosis in vitro. Here, we describe the global gene expression response to ectopic telomerase expression in an in vitro bovine adrenocortical cell model. Telomerase-immortalized cells showed an increased ability for proliferation and survival in minimal essential medium above cells transgenic for GFP. cDNA microarray analyses revealed an altered cell state indicative of increased adrenocortical cell proliferation regulated by the IGF2 pathway and alterations in members of the TGF-B family. As well, we identified alterations in genes associated with development and wound healing that support a model that high telomerase expression induces a highly adaptable, progenitor-like state.

  6. The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses.

    PubMed

    Stelzer, Gil; Rosen, Naomi; Plaschkes, Inbar; Zimmerman, Shahar; Twik, Michal; Fishilevich, Simon; Stein, Tsippi Iny; Nudel, Ron; Lieder, Iris; Mazor, Yaron; Kaplan, Sergey; Dahary, Dvir; Warshawsky, David; Guan-Golan, Yaron; Kohn, Asher; Rappaport, Noa; Safran, Marilyn; Lancet, Doron

    2016-06-20

    GeneCards, the human gene compendium, enables researchers to effectively navigate and inter-relate the wide universe of human genes, diseases, variants, proteins, cells, and biological pathways. Our recently launched Version 4 has a revamped infrastructure facilitating faster data updates, better-targeted data queries, and friendlier user experience. It also provides a stronger foundation for the GeneCards suite of companion databases and analysis tools. Improved data unification includes gene-disease links via MalaCards and merged biological pathways via PathCards, as well as drug information and proteome expression. VarElect, another suite member, is a phenotype prioritizer for next-generation sequencing, leveraging the GeneCards and MalaCards knowledgebase. It automatically infers direct and indirect scored associations between hundreds or even thousands of variant-containing genes and disease phenotype terms. VarElect's capabilities, either independently or within TGex, our comprehensive variant analysis pipeline, help prepare for the challenge of clinical projects that involve thousands of exome/genome NGS analyses. © 2016 by John Wiley & Sons, Inc.

  7. The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses.

    PubMed

    Stelzer, Gil; Rosen, Naomi; Plaschkes, Inbar; Zimmerman, Shahar; Twik, Michal; Fishilevich, Simon; Stein, Tsippi Iny; Nudel, Ron; Lieder, Iris; Mazor, Yaron; Kaplan, Sergey; Dahary, Dvir; Warshawsky, David; Guan-Golan, Yaron; Kohn, Asher; Rappaport, Noa; Safran, Marilyn; Lancet, Doron

    2016-01-01

    GeneCards, the human gene compendium, enables researchers to effectively navigate and inter-relate the wide universe of human genes, diseases, variants, proteins, cells, and biological pathways. Our recently launched Version 4 has a revamped infrastructure facilitating faster data updates, better-targeted data queries, and friendlier user experience. It also provides a stronger foundation for the GeneCards suite of companion databases and analysis tools. Improved data unification includes gene-disease links via MalaCards and merged biological pathways via PathCards, as well as drug information and proteome expression. VarElect, another suite member, is a phenotype prioritizer for next-generation sequencing, leveraging the GeneCards and MalaCards knowledgebase. It automatically infers direct and indirect scored associations between hundreds or even thousands of variant-containing genes and disease phenotype terms. VarElect's capabilities, either independently or within TGex, our comprehensive variant analysis pipeline, help prepare for the challenge of clinical projects that involve thousands of exome/genome NGS analyses. © 2016 by John Wiley & Sons, Inc. PMID:27322403

  8. PoplarGene: poplar gene network and resource for mining functional information for genes from woody plants.

    PubMed

    Liu, Qi; Ding, Changjun; Chu, Yanguang; Chen, Jiafei; Zhang, Weixi; Zhang, Bingyu; Huang, Qinjun; Su, Xiaohua

    2016-01-01

    Poplar is not only an important resource for the production of paper, timber and other wood-based products, but it has also emerged as an ideal model system for studying woody plants. To better understand the biological processes underlying various traits in poplar, e.g., wood development, a comprehensive functional gene interaction network is highly needed. Here, we constructed a genome-wide functional gene network for poplar (covering ~70% of the 41,335 poplar genes) and created the network web service PoplarGene, offering comprehensive functional interactions and extensive poplar gene functional annotations. PoplarGene incorporates two network-based gene prioritization algorithms, neighborhood-based prioritization and context-based prioritization, which can be used to perform gene prioritization in a complementary manner. Furthermore, the co-functional information in PoplarGene can be applied to other woody plant proteomes with high efficiency via orthology transfer. In addition to poplar gene sequences, the webserver also accepts Arabidopsis reference gene as input to guide the search for novel candidate functional genes in PoplarGene. We believe that PoplarGene (http://bioinformatics.caf.ac.cn/PoplarGene and http://124.127.201.25/PoplarGene) will greatly benefit the research community, facilitating studies of poplar and other woody plants. PMID:27515999

  9. PoplarGene: poplar gene network and resource for mining functional information for genes from woody plants

    PubMed Central

    Liu, Qi; Ding, Changjun; Chu, Yanguang; Chen, Jiafei; Zhang, Weixi; Zhang, Bingyu; Huang, Qinjun; Su, Xiaohua

    2016-01-01

    Poplar is not only an important resource for the production of paper, timber and other wood-based products, but it has also emerged as an ideal model system for studying woody plants. To better understand the biological processes underlying various traits in poplar, e.g., wood development, a comprehensive functional gene interaction network is highly needed. Here, we constructed a genome-wide functional gene network for poplar (covering ~70% of the 41,335 poplar genes) and created the network web service PoplarGene, offering comprehensive functional interactions and extensive poplar gene functional annotations. PoplarGene incorporates two network-based gene prioritization algorithms, neighborhood-based prioritization and context-based prioritization, which can be used to perform gene prioritization in a complementary manner. Furthermore, the co-functional information in PoplarGene can be applied to other woody plant proteomes with high efficiency via orthology transfer. In addition to poplar gene sequences, the webserver also accepts Arabidopsis reference gene as input to guide the search for novel candidate functional genes in PoplarGene. We believe that PoplarGene (http://bioinformatics.caf.ac.cn/PoplarGene and http://124.127.201.25/PoplarGene) will greatly benefit the research community, facilitating studies of poplar and other woody plants. PMID:27515999

  10. The future of Yellowcake: a global assessment of uranium resources and mining.

    PubMed

    Mudd, Gavin M

    2014-02-15

    Uranium (U) mining remains controversial in many parts of the world, especially in a post-Fukushima context, and often in areas with significant U resources. Although nuclear proponents point to the relatively low carbon intensity of nuclear power compared to fossil fuels, opponents argue that this will be eroded in the future as ore grades decline and energy and greenhouse gas emissions (GGEs) intensity increases as a result. Invariably both sides fail to make use of the increasingly available data reported by some U mines through sustainability reporting - allowing a comprehensive assessment of recent trends in the energy and GGE intensity of U production, as well as combining this with reported mineral resources to allow more comprehensive modelling of future energy and GGEs intensity. In this study, detailed data sets are compiled on reported U resources by deposit type, as well as mine production, energy and GGE intensity. Some important aspects included are the relationship between ore grade, deposit type and recovery, which are crucial in future projections of U mining. Overall, the paper demonstrates that there are extensive U resources known to meet potential short to medium term demand, although the future of U mining remains uncertain due to the doubt about the future of nuclear power as well as a range of complex social, environmental, economic and some site-specific technical issues. PMID:24317167

  11. The future of Yellowcake: a global assessment of uranium resources and mining.

    PubMed

    Mudd, Gavin M

    2014-02-15

    Uranium (U) mining remains controversial in many parts of the world, especially in a post-Fukushima context, and often in areas with significant U resources. Although nuclear proponents point to the relatively low carbon intensity of nuclear power compared to fossil fuels, opponents argue that this will be eroded in the future as ore grades decline and energy and greenhouse gas emissions (GGEs) intensity increases as a result. Invariably both sides fail to make use of the increasingly available data reported by some U mines through sustainability reporting - allowing a comprehensive assessment of recent trends in the energy and GGE intensity of U production, as well as combining this with reported mineral resources to allow more comprehensive modelling of future energy and GGEs intensity. In this study, detailed data sets are compiled on reported U resources by deposit type, as well as mine production, energy and GGE intensity. Some important aspects included are the relationship between ore grade, deposit type and recovery, which are crucial in future projections of U mining. Overall, the paper demonstrates that there are extensive U resources known to meet potential short to medium term demand, although the future of U mining remains uncertain due to the doubt about the future of nuclear power as well as a range of complex social, environmental, economic and some site-specific technical issues.

  12. EST mining of the UniGene dataset to identify retina-specific genes.

    PubMed

    Stöhr, H; Mah, N; Schulz, H L; Gehrig, A; Fröhlich, S; Weber, B H

    2000-01-01

    Age-related macular degeneration (AMD) is a multifactorial disorder affecting the visual system with a high prevalence among the elderly population but with no effective therapy available at present. To better understand the pathogenesis of this disorder, the identification of the genetic factors and the determination of their contribution to AMD is needed. Towards this goal, we are pursuing a strategy that makes use of the EST data processed in the UniGene database and aims at the generation of a comprehensive catalogue of genes preferentially active in the human retina. Subsequently, these genes will be systematically assessed in AMD. We performed a retina EST sampling and obtained a total of 673 clusters containing only retina ESTs as well as 568 clusters with at least 30% of the ESTs in each cluster originating from retina cDNA libraries. Of these, 180 representative EST clusters with varying retina and non-retina EST contents were analyzed for their in vitro expression. This approach identified 39 transcripts with retina-specific expression. One of these genes (C18orf2) mapping to chromosome 18 was further characterized. Multiple C18orf2 transcripts display a complex pattern of differential splicing in the human retina. The various isoforms encode hypothetical polypeptides with no homologies to known proteins or protein motifs.

  13. Gene mining in halophytes: functional identification of stress tolerance genes in Lepidium crassifolium.

    PubMed

    Rigó, Gábor; Valkai, Ildikó; Faragó, Dóra; Kiss, Edina; Van Houdt, Sara; Van de Steene, Nancy; Hannah, Matthew A; Szabados, László

    2016-09-01

    Extremophile plants are valuable sources of genes conferring tolerance traits, which can be explored to improve stress tolerance of crops. Lepidium crassifolium is a halophytic relative of the model plant Arabidopsis thaliana, and displays tolerance to salt, osmotic and oxidative stresses. We have employed the modified Conditional cDNA Overexpression System to transfer a cDNA library from L. crassifolium to the glycophyte A. thaliana. By screening for salt, osmotic and oxidative stress tolerance through in vitro growth assays and non-destructive chlorophyll fluorescence imaging, 20 Arabidopsis lines were identified with superior performance under restrictive conditions. Several cDNA inserts were cloned and confirmed to be responsible for the enhanced tolerance by analysing independent transgenic lines. Examples include full-length cDNAs encoding proteins with high homologies to GDSL-lipase/esterase or acyl CoA-binding protein or proteins without known function, which could confer tolerance to one or several stress conditions. Our results confirm that random gene transfer from stress tolerant to sensitive plant species is a valuable tool to discover novel genes with potential for biotechnological applications. PMID:27343166

  14. Phylogenetic Diversity of Archaea and the Archaeal Ammonia Monooxygenase Gene in Uranium Mining-Impacted Locations in Bulgaria

    PubMed Central

    Radeva, Galina; Kenarova, Anelia; Bachvarova, Velina; Popov, Ivan; Selenska-Pobell, Sonja

    2014-01-01

    Uranium mining and milling activities adversely affect the microbial populations of impacted sites. The negative effects of uranium on soil bacteria and fungi are well studied, but little is known about the effects of radionuclides and heavy metals on archaea. The composition and diversity of archaeal communities inhabiting the waste pile of the Sliven uranium mine and the soil of the Buhovo uranium mine were investigated using 16S rRNA gene retrieval. A total of 355 archaeal clones were selected, and their 16S rDNA inserts were analysed by restriction fragment length polymorphism (RFLP) discriminating 14 different RFLP types. All evaluated archaeal 16S rRNA gene sequences belong to the 1.1b/Nitrososphaera cluster of Crenarchaeota. The composition of the archaeal community is distinct for each site of interest and dependent on environmental characteristics, including pollution levels. Since the members of 1.1b/Nitrososphaera cluster have been implicated in the nitrogen cycle, the archaeal communities from these sites were probed for the presence of the ammonia monooxygenase gene (amoA). Our data indicate that amoA gene sequences are distributed in a similar manner as in Crenarchaeota, suggesting that archaeal nitrification processes in uranium mining-impacted locations are under the control of the same key factors controlling archaeal diversity. PMID:24711725

  15. Literature mining for the discovery of hidden connections between drugs, genes and diseases.

    PubMed

    Frijters, Raoul; van Vugt, Marianne; Smeets, Ruben; van Schaik, René; de Vlieg, Jacob; Alkema, Wynand

    2010-09-23

    The scientific literature represents a rich source for retrieval of knowledge on associations between biomedical concepts such as genes, diseases and cellular processes. A commonly used method to establish relationships between biomedical concepts from literature is co-occurrence. Apart from its use in knowledge retrieval, the co-occurrence method is also well-suited to discover new, hidden relationships between biomedical concepts following a simple ABC-principle, in which A and C have no direct relationship, but are connected via shared B-intermediates. In this paper we describe CoPub Discovery, a tool that mines the literature for new relationships between biomedical concepts. Statistical analysis using ROC curves showed that CoPub Discovery performed well over a wide range of settings and keyword thesauri. We subsequently used CoPub Discovery to search for new relationships between genes, drugs, pathways and diseases. Several of the newly found relationships were validated using independent literature sources. In addition, new predicted relationships between compounds and cell proliferation were validated and confirmed experimentally in an in vitro cell proliferation assay. The results show that CoPub Discovery is able to identify novel associations between genes, drugs, pathways and diseases that have a high probability of being biologically valid. This makes CoPub Discovery a useful tool to unravel the mechanisms behind disease, to find novel drug targets, or to find novel applications for existing drugs.

  16. Novel Nickel Resistance Genes from the Rhizosphere Metagenome of Plants Adapted to Acid Mine Drainage▿ †

    PubMed Central

    Mirete, Salvador; de Figueras, Carolina G.; González-Pastor, Jose E.

    2007-01-01

    Metal resistance determinants have traditionally been found in cultivated bacteria. To search for genes involved in nickel resistance, we analyzed the bacterial community of the rhizosphere of Erica andevalensis, an endemic heather which grows at the banks of the Tinto River, a naturally metal-enriched and extremely acidic environment in southwestern Spain. 16S rRNA gene sequence analysis of rhizosphere DNA revealed the presence of members of five phylogenetic groups of Bacteria and the two main groups of Archaea mostly associated with sites impacted by acid mine drainage (AMD). The diversity observed and the presence of heavy metals in the rhizosphere led us to construct and screen five different metagenomic libraries hosted in Escherichia coli for searching novel nickel resistance determinants. A total of 13 positive clones were detected and analyzed. Insights about their possible mechanisms of resistance were obtained from cellular nickel content and sequence similarities. Two clones encoded putative ABC transporter components, and a novel mechanism of metal efflux is suggested. In addition, a nickel hyperaccumulation mechanism is proposed for a clone encoding a serine O-acetyltransferase. Five clones encoded proteins similar to well-characterized proteins but not previously reported to be related to nickel resistance, and the remaining six clones encoded hypothetical or conserved hypothetical proteins of uncertain functions. This is the first report documenting nickel resistance genes recovered from the metagenome of an AMD environment. PMID:17675438

  17. Phylogenomic study of lipid genes involved in microalgal biofuel production-candidate gene mining and metabolic pathway analyses.

    PubMed

    Misra, Namrata; Panda, Prasanna Kumar; Parida, Bikram Kumar; Mishra, Barada Kanta

    2012-01-01

    Optimizing microalgal biofuel production using metabolic engineering tools requires an in-depth understanding of the structure-function relationship of genes involved in lipid biosynthetic pathway. In the present study, genome-wide identification and characterization of 398 putative genes involved in lipid biosynthesis in Arabidopsis thaliana Chlamydomonas reinhardtii, Volvox carteri, Ostreococcus lucimarinus, Ostreococcus tauri and Cyanidioschyzon merolae was undertaken on the basis of their conserved motif/domain organization and phylogenetic profile. The results indicated that the core lipid metabolic pathways in all the species are carried out by a comparable number of orthologous proteins. Although the fundamental gene organizations were observed to be invariantly conserved between microalgae and Arabidopsis genome, with increased order of genome complexity there seems to be an association with more number of genes involved in triacylglycerol (TAG) biosynthesis and catabolism. Further, phylogenomic analysis of the genes provided insights into the molecular evolution of lipid biosynthetic pathway in microalgae and confirm the close evolutionary proximity between the Streptophyte and Chlorophyte lineages. Together, these studies will improve our understanding of the global lipid metabolic pathway and contribute to the engineering of regulatory networks of algal strains for higher accumulation of oil. PMID:23032611

  18. Identification of candidate genes in Populus cell wall biosynthesis using text-mining, co-expression network and comparative genomics

    SciTech Connect

    Yang, Xiaohan; Ye, Chuyu; Bisaria, Anjali; Tuskan, Gerald A; Kalluri, Udaya C

    2011-01-01

    Populus is an important bioenergy crop for bioethanol production. A greater understanding of cell wall biosynthesis processes is critical in reducing biomass recalcitrance, a major hindrance in efficient generation of ethanol from lignocellulosic biomass. Here, we report the identification of candidate cell wall biosynthesis genes through the development and application of a novel bioinformatics pipeline. As a first step, via text-mining of PubMed publications, we obtained 121 Arabidopsis genes that had the experimental evidences supporting their involvement in cell wall biosynthesis or remodeling. The 121 genes were then used as bait genes to query an Arabidopsis co-expression database and additional genes were identified as neighbors of the bait genes in the network, increasing the number of genes to 548. The 548 Arabidopsis genes were then used to re-query the Arabidopsis co-expression database and re-construct a network that captured additional network neighbors, expanding to a total of 694 genes. The 694 Arabidopsis genes were computationally divided into 22 clusters. Queries of the Populus genome using the Arabidopsis genes revealed 817 Populus orthologs. Functional analysis of gene ontology and tissue-specific gene expression indicated that these Arabidopsis and Populus genes are high likelihood candidates for functional genomics in relation to cell wall biosynthesis.

  19. Mining the Present: Reconstructing Progressive Education in an Era of Global Change

    ERIC Educational Resources Information Center

    Edwards, Laura A.; Greenwalt, Kyle A.

    2013-01-01

    This paper explores what might be seen as a paradox at the heart of the current push to "globalize" education: at a moment when administrators, especially in higher education, are seeking to globalize their programs (often for reasons having to do with increasing international competition and decreasing funding for education), global…

  20. Advances in genetic circuit design: novel biochemistries, deep part mining, and precision gene expression.

    PubMed

    Nielsen, Alec A K; Segall-Shapiro, Thomas H; Voigt, Christopher A

    2013-12-01

    Cells use regulatory networks to perform computational operations to respond to their environment. Reliably manipulating such networks would be valuable for many applications in biotechnology; for example, in having genes turn on only under a defined set of conditions or implementing dynamic or temporal control of expression. Still, building such synthetic regulatory circuits remains one of the most difficult challenges in genetic engineering and as a result they have not found widespread application. Here, we review recent advances that address the key challenges in the forward design of genetic circuits. First, we look at new design concepts, including the construction of layered digital and analog circuits, and new approaches to control circuit response functions. Second, we review recent work to apply part mining and computational design to expand the number of regulators that can be used together within one cell. Finally, we describe new approaches to obtain precise gene expression and to reduce context dependence that will accelerate circuit design by more reliably balancing regulators while reducing toxicity.

  1. The Algorithm of Development the World Ocean Mining of the Industry During the Global Crisis

    NASA Astrophysics Data System (ADS)

    Nyrkov, Anatoliy; Budnik, Vladislav; Sokolov, Sergei; Chernyi, Sergei

    2016-08-01

    In the article reviewed extraction effect of hydrocarbons on the general country's developing, under the impact of economical, demographical and technological factors, as well as it's future role in the world energy balance. Also adduced facts which designate offshore and deep water production of unconventional and conventional hydrocarbons including mining of marine mineral resources as perspective area of development in the future, despite all the difficulties of this sector. In the article considered the state and prospects of the Russian continental shelf, in consideration of its geographical location and its all existing problems.

  2. Global identification of bursicon-regulated genes in Drosophila melanogaster

    PubMed Central

    An, Shiheng; Wang, Songjie; Gilbert, Lawrence I; Beerntsen, Brenda; Ellersieck, Mark; Song, Qisheng

    2008-01-01

    Background Bursicon is a heterodimer neuropeptide responsible for regulating cuticle sclerotization and wing expansion in several insect species. Recent studies indicate that the action of bursicon is mediated by a specific G protein-coupled receptor DLGR2 and the cAMP/PKA signaling pathway. However, little is known regarding the genes that are regulated by bursicon. The identification of bursicon-regulated genes is the focus of this investigation. Results We used DNA microarray analysis to identify bursicon-regulated genes in neck-ligated flies (Drosophila melanogaster) that received recombinant bursicon (r-bursicon). Fifty four genes were found to be regulated by bursicon 1 h post r-bursicon injection, 52 being up-regulated and 2 down-regulated while 33 genes were influenced by r-bursicon 3 h post-injection (24 up-regulated and 9 down-regulated genes). Analysis of these genes by inference from the fly database revealed that these genes encode proteins with diverse functions, including cell signaling, gene transcription, DNA/RNA binding, ion trafficking, proteolysis-peptidolysis, metabolism, cytoskeleton formation, immune response and cell-adhesion. Twenty eight genes randomly selected from the microarray-identified list were verified by real time PCR (qPCR) which supported the microarray data. Temporal response studies of 13 identified and verified genes by qPCR revealed that the temporal expression patterns of these genes are consistent with the microarray data. Conclusion Using r-bursicon, we identified 87 genes that are regulated by bursicon, 30 of which have no previously known function. Most importantly, all genes randomly selected from the microarray-identified list were verified by real time PCR. Temporal analysis of 13 verified genes revealed that the expression of these genes was indeed induced by bursicon and correlated well with the cuticle sclerotization process. The composite data suggest that these genes play important roles in regulating the

  3. Global gene expression profiles in developing soybean seeds.

    PubMed

    Asakura, Tomiko; Tamura, Tomoko; Terauchi, Kaede; Narikawa, Tomoyo; Yagasaki, Kazuhiro; Ishimaru, Yoshiro; Abe, Keiko

    2012-03-01

    The gene expression profiles in soybean (Glycine max L.) seeds at 4 stages of development, namely, pod, 2-mm bean, 5-mm bean, and full-size bean, were examined by DNA microarray analysis. The total genes of each sample were classified into 4 clusters based on stage of development. Gene expression was strictly controlled by seed size, which coincides with the development stage. First, stage specific gene expression was examined. Many transcription factors were expressed in pod, 2-mm bean and 5-mm bean. In contrast, storage proteins were mainly expressed in full-size bean. Next, we extracted the genes that are differentially expressed genes (DEGs) that were extracted using the Rank products method of the Bioconductor software package. These DEGs were sorted into 8 groups using the hclust function according to gene expression patterns. Three of the groups across which the expression levels progressively increased included 100 genes, while 3 groups across which the levels decreased contained 47 genes. Storage proteins, seed-maturation proteins, some protease inhibitors, and the allergen Gly m Bd 28K were classified into the former groups. Lipoxygenase (LOX) family members were present in both the groups, indicating the multi-functionality with different expression patterns. PMID:22245912

  4. The Influence of the Global Gene Expression Shift on Downstream Analyses

    PubMed Central

    Xu, Qifeng; Zhang, Xuegong

    2016-01-01

    The assumption that total abundance of RNAs in a cell is roughly the same in different cells is underlying most studies based on gene expression analyses. But experiments have shown that changes in the expression of some master regulators such as c-MYC can cause global shift in the expression of almost all genes in some cell types like cancers. Such shift will violate this assumption and can cause wrong or biased conclusions for standard data analysis practices, such as detection of differentially expressed (DE) genes and molecular classification of tumors based on gene expression. Most existing gene expression data were generated without considering this possibility, and are therefore at the risk of having produced unreliable results if such global shift effect exists in the data. To evaluate this risk, we conducted a systematic study on the possible influence of the global gene expression shift effect on differential expression analysis and on molecular classification analysis. We collected data with known global shift effect and also generated data to simulate different situations of the effect based on a wide collection of real gene expression data, and conducted comparative studies on representative existing methods. We observed that some DE analysis methods are more tolerant to the global shift while others are very sensitive to it. Classification accuracy is not sensitive to the shift and actually can benefit from it, but genes selected for the classification can be greatly affected. PMID:27092944

  5. Global analysis of patterns of gene expression during Drosophila embryogenesis

    PubMed Central

    Tomancak, Pavel; Berman, Benjamin P; Beaton, Amy; Weiszmann, Richard; Kwan, Elaine; Hartenstein, Volker; Celniker, Susan E; Rubin, Gerald M

    2007-01-01

    Background Cell and tissue specific gene expression is a defining feature of embryonic development in multi-cellular organisms. However, the range of gene expression patterns, the extent of the correlation of expression with function, and the classes of genes whose spatial expression are tightly regulated have been unclear due to the lack of an unbiased, genome-wide survey of gene expression patterns. Results We determined and documented embryonic expression patterns for 6,003 (44%) of the 13,659 protein-coding genes identified in the Drosophila melanogaster genome with over 70,000 images and controlled vocabulary annotations. Individual expression patterns are extraordinarily diverse, but by supplementing qualitative in situ hybridization data with quantitative microarray time-course data using a hybrid clustering strategy, we identify groups of genes with similar expression. Of 4,496 genes with detectable expression in the embryo, 2,549 (57%) fall into 10 clusters representing broad expression patterns. The remaining 1,947 (43%) genes fall into 29 clusters representing restricted expression, 20% patterned as early as blastoderm, with the majority restricted to differentiated cell types, such as epithelia, nervous system, or muscle. We investigate the relationship between expression clusters and known molecular and cellular-physiological functions. Conclusion Nearly 60% of the genes with detectable expression exhibit broad patterns reflecting quantitative rather than qualitative differences between tissues. The other 40% show tissue-restricted expression; the expression patterns of over 1,500 of these genes are documented here for the first time. Within each of these categories, we identified clusters of genes associated with particular cellular and developmental functions. PMID:17645804

  6. Assessment of Local Biodiversity Loss in Uranium Mining-Tales And Its Projections On Global Scale

    NASA Astrophysics Data System (ADS)

    Sharshenova, D.; Zhamangulova, N.

    2015-12-01

    In Min-Kush, northern Kyrgyzstan there are 8 mining tales with an estimate of 1 961 000 tones of industrial Uranium. Local ecosystem services have declined rapidly. We analyzed a terrestrial assemblage database of Uranium mine-tale to quantify local biodiversity responses to land use and environmental changes. In the worst-affected habitats species richness reduced by 95.7%, total abundance by 60.9% and rarefaction-based richness by 72.5%. We estimate that, regional mountain ecosystem affected by this pressure reduced average within-sample richness (by 17.01%), total abundance (16.5%) and rarefaction-based richness (14.5%). Business-as-usual scenarios are the widely practiced in the region and moreover, due to economic constraints country can not afford any mitigation scenarios. We project that biodiversity loss and ecosystem service impairment will spread in the region through ground water, soil, plants, animals and microorganisms at the rate of 1km/year. Entire Tian-Shan mountain chain will be in danger within next 5-10 years. Our preliminary data shows that local people live in this area developed various forms of cancer, and the rate of premature death is as high as 40%. Strong international scientific and socio-economic partnership is needed to develop models and predictions.

  7. Your Place or Mine? Global Imbalances in Internationalisation and Mobilisation in Educational Professional Experience

    ERIC Educational Resources Information Center

    Buchanan, John; Widodo, Ari

    2016-01-01

    International mobility programmes and opportunities have enthusiastically been embraced by universities as part of a growing demand for graduates with global, international and intercultural capital on the part of graduates. In this project, we take two universities, one Australian and one Indonesian, as illustrative case studies of some of the…

  8. A GLOBAL METHANE EMISSIONS PROGRAM FOR LANDFILLS, COAL MINES, AND NATURAL GAS SYSTEMS

    EPA Science Inventory

    The paper gives the scope and methodology of EPA/AEERL's methane emissions studies and discloses data accumulated thus far in the program. Anthropogenic methane emissions are a principal focus in AEERL's global climate research program, including three major sources: municipal so...

  9. Global demand for rare earth resources and strategies for green mining

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rare earths elements (REEs) are essential raw materials for the emerging green (low-carbon) energy technologies and ‘smart’ electronic devices. Global REE demand is slated to grow at a compound annual rate of 5% by 2020. Such high growth rate would require a steady supply base of REEs in the long ru...

  10. Global Identification of Genes Specific for Rice Meiosis

    PubMed Central

    Zhang, Bingwei; Xu, Meng; Bian, Shiquan; Hou, Lili; Tang, Ding; Li, Yafei; Gu, Minghong; Cheng, Zhukuan; Yu, Hengxiu

    2015-01-01

    The leptotene-zygotene transition is a major step in meiotic progression during which pairing between homologous chromosomes is initiated and double strand breaks occur. OsAM1, a homologue of maize AM1 and Arabidopsis SWI1, encodes a protein with a coiled-coil domain in its central region that is required for the leptotene-zygotene transition during rice meiosis. To gain more insight into the role of OsAM1 in rice meiosis and identify additional meiosis-specific genes, we characterized the transcriptomes of young panicles of Osam1 mutant and wild-type rice plants using RNA-Seq combined with bioinformatic and statistical analyses. As a result, a total of 25,750 and 28,455 genes were expressed in young panicles of wild-type and Osam1 mutant plants, respectively, and 4,400 differentially expressed genes (DEGs; log2 Ratio ≥ 1, FDR ≤ 0.05) were identified. Of these DEGs, four known rice meiosis-specific genes were detected, and 22 new putative meiosis-related genes were found by mapping these DEGs to reference biological pathways in the KEGG database. We identified eight additional well-conserved OsAM1-responsive rice meiotic genes by comparing our RNA-Seq data with known meiotic genes in Arabidopsis and fission yeast. PMID:26394329

  11. Global Identification of Genes Specific for Rice Meiosis.

    PubMed

    Zhang, Bingwei; Xu, Meng; Bian, Shiquan; Hou, Lili; Tang, Ding; Li, Yafei; Gu, Minghong; Cheng, Zhukuan; Yu, Hengxiu

    2015-01-01

    The leptotene-zygotene transition is a major step in meiotic progression during which pairing between homologous chromosomes is initiated and double strand breaks occur. OsAM1, a homologue of maize AM1 and Arabidopsis SWI1, encodes a protein with a coiled-coil domain in its central region that is required for the leptotene-zygotene transition during rice meiosis. To gain more insight into the role of OsAM1 in rice meiosis and identify additional meiosis-specific genes, we characterized the transcriptomes of young panicles of Osam1 mutant and wild-type rice plants using RNA-Seq combined with bioinformatic and statistical analyses. As a result, a total of 25,750 and 28,455 genes were expressed in young panicles of wild-type and Osam1 mutant plants, respectively, and 4,400 differentially expressed genes (DEGs; log2 Ratio ≥ 1, FDR ≤ 0.05) were identified. Of these DEGs, four known rice meiosis-specific genes were detected, and 22 new putative meiosis-related genes were found by mapping these DEGs to reference biological pathways in the KEGG database. We identified eight additional well-conserved OsAM1-responsive rice meiotic genes by comparing our RNA-Seq data with known meiotic genes in Arabidopsis and fission yeast.

  12. The use and re-use of unsustainably mined groundwater: A global budget

    NASA Astrophysics Data System (ADS)

    Grogan, D. S.; Prousevitch, A.; Wisser, D.; Lammers, R. B.; Frolking, S. E.

    2015-12-01

    Many of the world's major groundwater aquifers are rapidly depleting due to unsustainable groundwater pumping, while demand for food production - and therefore demand for irrigation water ­- is increasing. While it is likely that groundwater users will be impacted by the future's inevitable reduction in groundwater availability, there is a major gap in our understanding of potential impacts downstream of pumping sites. Due to inefficiencies in irrigation systems, significant amounts of abstracted groundwater become runoff, entering surface waters and flowing downstream to be re-abstracted and used again. In this study, we use a gridded water balance model to calculate the amount of unsustainably pumped groundwater that enters surface water systems by way of irrigation runoff, and quantify the additional irrigation water supplied by the re-use of this water. We assess the global budget of unsustainable groundwater sources and sinks, including downstream re-use, groundwater recharge, and flow to the oceans. Globally, we find that 80% of unsustainable groundwater is re-abstracted for irrigation either downstream or locally from groundwater recharge. This re-abstracted water contributes the water equivalent needed to irrigate 200,000 km2 of cropland globally. Including irrigation runoff reuse in an assessment of irrigation efficiency, we see that the traditional concept of irrigation efficiency (net irrigation/gross irrigation) significantly overestimates water "waste". We define a basin efficiency for unsustainable groundwater use that includes re-use, and see that while global irrigation efficiency is often estimated at 50%, global average unsustainable water use efficiency is > 60%. Losing this re-use resource by increasing irrigation efficiency does little to alleviate unsustainable groundwater demands.

  13. bc-GenExMiner 3.0: new mining module computes breast cancer gene expression correlation analyses.

    PubMed

    Jézéquel, Pascal; Frénel, Jean-Sébastien; Campion, Loïc; Guérin-Charbonnel, Catherine; Gouraud, Wilfried; Ricolleau, Gabriel; Campone, Mario

    2013-01-01

    We recently developed a user-friendly web-based application called bc-GenExMiner (http://bcgenex.centregauducheau.fr), which offered the possibility to evaluate prognostic informativity of genes in breast cancer by means of a 'prognostic module'. In this study, we develop a new module called 'correlation module', which includes three kinds of gene expression correlation analyses. The first one computes correlation coefficient between 2 or more (up to 10) chosen genes. The second one produces two lists of genes that are most correlated (positively and negatively) to a 'tested' gene. A gene ontology (GO) mining function is also proposed to explore GO 'biological process', 'molecular function' and 'cellular component' terms enrichment for the output lists of most correlated genes. The third one explores gene expression correlation between the 15 telomeric and 15 centromeric genes surrounding a 'tested' gene. These correlation analyses can be performed in different groups of patients: all patients (without any subtyping), in molecular subtypes (basal-like, HER2+, luminal A and luminal B) and according to oestrogen receptor status. Validation tests based on published data showed that these automatized analyses lead to results consistent with studies' conclusions. In brief, this new module has been developed to help basic researchers explore molecular mechanisms of breast cancer. DATABASE URL: http://bcgenex.centregauducheau.fr

  14. Computational Genomics: From Genome Sequence To Global Gene Regulation

    NASA Astrophysics Data System (ADS)

    Li, Hao

    2000-03-01

    As various genome projects are shifting to the post-sequencing phase, it becomes a big challenge to analyze the sequence data and extract biological information using computational tools. In the past, computational genomics has mainly focused on finding new genes and mapping out their biological functions. With the rapid accumulation of experimental data on genome-wide gene activities, it is now possible to understand how genes are regulated on a genomic scale. A major mechanism for gene regulation is to control the level of transcription, which is achieved by regulatory proteins that bind to short DNA sequences - the regulatory elements. We have developed a new approach to identifying regulatory elements in genomes. The approach formalizes how one would proceed to decipher a ``text'' consisting of a long string of letters written in an unknown language that did not delineate words. The algorithm is based on a statistical mechanics model in which the sequence is segmented probabilistically into ``words'' and a ``dictionary'' of ``words'' is built concurrently. For the control regions in the yeast genome, we built a ``dictionary'' of about one thousand words which includes many known as well as putative regulatory elements. I will discuss how we can use this dictionary to search for genes that are likely to be regulated in a similar fashion and to analyze gene expression data generated from DNA micro-array experiments.

  15. Contribution of Spanish-American silver mines (1570-1820) to the present high mercury concentrations in the global environment: a review.

    PubMed

    Camargo, Julio A

    2002-07-01

    In this review I evaluate the contribution of Spanish-American silver mines during the period 1570-1820 (a Spanish colonial period of 250 years) to the present high mercury concentrations in the global environment. The evaluation is based upon the following bibliographic information: (1) total amount of mercury consumed in Spanish-American silver mines between 1570 and 1820; (2) percentage of the total amount of mercury consumed in Spanish-American silver mines that may have been emitted to the atmosphere; (3) global natural input of mercury to the atmosphere; (4) worldwide anthropogenic emissions of mercury to the atmosphere; (5) residence time of mercury in the atmosphere; and (6) capacity of mercury to be deposited in the sediments of aquatic systems. From all this information, and owing to the relatively long time that has passed since Spanish-American silver mines were operational, I conclude that most of the mercury lost during the refining of silver via the patio amalgamation process is now sequestered into the sediments of aquatic systems, mainly in marine sediments. The high mercury concentrations now being reported in the global environment essentially are a consequence of the huge pollution caused by human activities during the past 20th century.

  16. Identification of Novel Target Genes for Safer and More Specific Control of Root-Knot Nematodes from a Pan-Genome Mining

    PubMed Central

    Danchin, Etienne G. J.; Perfus-Barbeoch, Laetitia; Magliano, Marc; Rosso, Marie-Noëlle; Da Rocha, Martine; Da Silva, Corinne; Nottet, Nicolas; Labadie, Karine; Guy, Julie; Artiguenave, François; Abad, Pierre

    2013-01-01

    Root-knot nematodes are globally the most aggressive and damaging plant-parasitic nematodes. Chemical nematicides have so far constituted the most efficient control measures against these agricultural pests. Because of their toxicity for the environment and danger for human health, these nematicides have now been banned from use. Consequently, new and more specific control means, safe for the environment and human health, are urgently needed to avoid worldwide proliferation of these devastating plant-parasites. Mining the genomes of root-knot nematodes through an evolutionary and comparative genomics approach, we identified and analyzed 15,952 nematode genes conserved in genomes of plant-damaging species but absent from non target genomes of chordates, plants, annelids, insect pollinators and mollusks. Functional annotation of the corresponding proteins revealed a relative abundance of putative transcription factors in this parasite-specific set compared to whole proteomes of root-knot nematodes. This may point to important and specific regulators of genes involved in parasitism. Because these nematodes are known to secrete effector proteins in planta, essential for parasitism, we searched and identified 993 such effector-like proteins absent from non-target species. Aiming at identifying novel targets for the development of future control methods, we biologically tested the effect of inactivation of the corresponding genes through RNA interference. A total of 15 novel effector-like proteins and one putative transcription factor compatible with the design of siRNAs were present as non-redundant genes and had transcriptional support in the model root-knot nematode Meloidogyne incognita. Infestation assays with siRNA-treated M. incognita on tomato plants showed significant and reproducible reduction of the infestation for 12 of the 16 tested genes compared to control nematodes. These 12 novel genes, showing efficient reduction of parasitism when silenced, constitute

  17. Isolation and characterisation of mineral-oxidising "Acidibacillus" spp. from mine sites and geothermal environments in different global locations.

    PubMed

    Holanda, Roseanne; Hedrich, Sabrina; Ňancucheo, Ivan; Oliveira, Guilherme; Grail, Barry M; Johnson, D Barrie

    2016-09-01

    Eight strains of acidophilic bacteria, isolated from mine-impacted and geothermal sites from different parts of the world, were shown to form a distinct clade (proposed genus "Acidibacillus") within the phylum Firmicutes, well separated from the acidophilic genera Sulfobacillus and Alicyclobacillus. Two of the strains (both isolated from sites in Yellowstone National Park, USA) were moderate thermophiles that oxidised both ferrous iron and elemental sulphur, while the other six were mesophiles that also oxidised ferrous iron, but not sulphur. All eight isolates reduced ferric iron to varying degrees. The two groups shared <95% similarity of their 16S rRNA genes and were therefore considered to be distinct species: "Acidibacillus sulfuroxidans" (moderately thermophilic isolates) and "Acidibacillus ferrooxidans" (mesophilic isolates). Both species were obligate heterotrophs; none of the eight strains grew in the absence of organic carbon. "Acidibacillus" spp. were generally highly tolerant of elevated concentrations of cationic transition metals, though "A. sulfuroxidans" strains were more sensitive to some (e.g. nickel and zinc) than those of "A. ferrooxidans". Initial annotation of the genomes of two strains of "A. ferrooxidans" revealed the presence of genes (cbbL) involved in the RuBisCO pathway for CO2 assimilation and iron oxidation (rus), though with relatively low sequence identities. PMID:27154030

  18. Isolation and characterisation of mineral-oxidising "Acidibacillus" spp. from mine sites and geothermal environments in different global locations.

    PubMed

    Holanda, Roseanne; Hedrich, Sabrina; Ňancucheo, Ivan; Oliveira, Guilherme; Grail, Barry M; Johnson, D Barrie

    2016-09-01

    Eight strains of acidophilic bacteria, isolated from mine-impacted and geothermal sites from different parts of the world, were shown to form a distinct clade (proposed genus "Acidibacillus") within the phylum Firmicutes, well separated from the acidophilic genera Sulfobacillus and Alicyclobacillus. Two of the strains (both isolated from sites in Yellowstone National Park, USA) were moderate thermophiles that oxidised both ferrous iron and elemental sulphur, while the other six were mesophiles that also oxidised ferrous iron, but not sulphur. All eight isolates reduced ferric iron to varying degrees. The two groups shared <95% similarity of their 16S rRNA genes and were therefore considered to be distinct species: "Acidibacillus sulfuroxidans" (moderately thermophilic isolates) and "Acidibacillus ferrooxidans" (mesophilic isolates). Both species were obligate heterotrophs; none of the eight strains grew in the absence of organic carbon. "Acidibacillus" spp. were generally highly tolerant of elevated concentrations of cationic transition metals, though "A. sulfuroxidans" strains were more sensitive to some (e.g. nickel and zinc) than those of "A. ferrooxidans". Initial annotation of the genomes of two strains of "A. ferrooxidans" revealed the presence of genes (cbbL) involved in the RuBisCO pathway for CO2 assimilation and iron oxidation (rus), though with relatively low sequence identities.

  19. Distinctive features of plant organs characterized by global analysis of gene expression in Arabidopsis.

    PubMed

    Obayashi, Takeshi; Okegawa, Takashi; Sasaki-Sekimoto, Yuko; Shimada, Hiroshi; Masuda, Tatsuru; Asamizu, Erika; Nakamura, Yasukazu; Shibata, Daisuke; Tabata, Satoshi; Takamiya, Ken-ichiro; Ohta, Hiroyuki

    2004-02-29

    The distinctive features of plant organs are primarily determined by organ-specific gene expression. We analyzed the expression specificity of 8809 genes in 7 organs of Arabidopsis using a cDNA macroarray system. Using relative expression (RE) values between organs, many known and unknown genes specifically expressed in each organ were identified. We also analyzed the organ specificity of various gene groups using the GRE (group relative expression) value, the average of the REs of all genes in a group. Consequently, we found that many gene groups even ribosomal protein genes, have strong organ-specific expression. Clustering of the expression profiles revealed that the 8809 genes were classified into 9 major categories. Although 3451 genes were clustered into the largest category, which showed constitutive gene expression, 266 and 1005 genes were found to be root- and silique-specific genes, respectively. By this clustering, particular gene groups which showed multi-organ-specific expression profiles, such as bud-flower-specific, stem-silique-specific or bud-flower-root-specific profiles, could be effectively identified. From these results, major features of plant organs could be characterized by their distinct profiles of global gene expression. These data of organ-specific gene expression are available at our web site: Arabidopsis thaliana Tissue-Specific Expression Database, ATTED (http://www.atted.bio.titech.ac.jp/).

  20. SNP Mining in Functional Genes from Nonmodel Species by Next-Generation Sequencing: A Case of Flowering, Pre-Harvest Sprouting, and Dehydration Resistant Genes in Wheat

    PubMed Central

    Chen, Zhong-Xu; Deng, Mei

    2016-01-01

    As plenty of nonmodel plants are without genomic sequences, the combination of molecular technologies and the next generation sequencing (NGS) platform has led to a new approach to study the genetic variations of these plants. Software GATK, SOAPsnp, samtools, and others are often used to deal with the NGS data. In this study, BLAST was applied to call SNPs from 16 mixed functional gene's sequence data of polyploidy wheat. In total 1.2 million reads were obtained with the average of 7500 reads per genes. To get accurate information, 390,992 pair reads were successfully assembled before aligning to those functional genes. Standalone BLAST tools were used to map assembled sequence to functional genes, respectively. Polynomial fitting was applied to find the suitable minor allele frequency (MAF) threshold at 6% for assembled reads of each functional gene. SNPs accuracy form assembled reads, pretrimmed reads, and original reads were compared, which declared that SNPs mined from the assembled reads were more reliable than others. It was also demonstrated that mixed samples' NGS sequences and then analysis by BLAST were an effective, low-cost, and accurate way to mine SNPs for nonmodel species. Assembled reads and polynomial fitting threshold were recommended for more accurate SNPs target. PMID:27051662

  1. TCMGeneDIT: a database for associated traditional Chinese medicine, gene and disease information using text mining

    PubMed Central

    Fang, Yu-Ching; Huang, Hsuan-Cheng; Chen, Hsin-Hsi; Juan, Hsueh-Fen

    2008-01-01

    Background Traditional Chinese Medicine (TCM), a complementary and alternative medical system in Western countries, has been used to treat various diseases over thousands of years in East Asian countries. In recent years, many herbal medicines were found to exhibit a variety of effects through regulating a wide range of gene expressions or protein activities. As available TCM data continue to accumulate rapidly, an urgent need for exploring these resources systematically is imperative, so as to effectively utilize the large volume of literature. Methods TCM, gene, disease, biological pathway and protein-protein interaction information were collected from public databases. For association discovery, the TCM names, gene names, disease names, TCM ingredients and effects were used to annotate the literature corpus obtained from PubMed. The concept to mine entity associations was based on hypothesis testing and collocation analysis. The annotated corpus was processed with natural language processing tools and rule-based approaches were applied to the sentences for extracting the relations between TCM effecters and effects. Results We developed a database, TCMGeneDIT, to provide association information about TCMs, genes, diseases, TCM effects and TCM ingredients mined from vast amount of biomedical literature. Integrated protein-protein interaction and biological pathways information are also available for exploring the regulations of genes associated with TCM curative effects. In addition, the transitive relationships among genes, TCMs and diseases could be inferred through the shared intermediates. Furthermore, TCMGeneDIT is useful in understanding the possible therapeutic mechanisms of TCMs via gene regulations and deducing synergistic or antagonistic contributions of the prescription components to the overall therapeutic effects. The database is now available at . Conclusion TCMGeneDIT is a unique database that offers diverse association information on TCMs. This

  2. Cell types differ in global coordination of splicing and proportion of highly expressed genes.

    PubMed

    Trakhtenberg, Ephraim F; Pho, Nam; Holton, Kristina M; Chittenden, Thomas W; Goldberg, Jeffrey L; Dong, Lingsheng

    2016-01-01

    Balance in the transcriptome is regulated by coordinated synthesis and degradation of RNA molecules. Here we investigated whether mammalian cell types intrinsically differ in global coordination of gene splicing and expression levels. We analyzed RNA-seq transcriptome profiles of 8 different purified mouse cell types. We found that different cell types vary in proportion of highly expressed genes and the number of alternatively spliced transcripts expressed per gene, and that the cell types that express more variants of alternatively spliced transcripts per gene are those that have higher proportion of highly expressed genes. Cell types segregated into two clusters based on high or low proportion of highly expressed genes. Biological functions involved in negative regulation of gene expression were enriched in the group of cell types with low proportion of highly expressed genes, and biological functions involved in regulation of transcription and RNA splicing were enriched in the group of cell types with high proportion of highly expressed genes. Our findings show that cell types differ in proportion of highly expressed genes and the number of alternatively spliced transcripts expressed per gene, which represent distinct properties of the transcriptome and may reflect intrinsic differences in global coordination of synthesis, splicing, and degradation of RNA molecules. PMID:27577089

  3. Cell types differ in global coordination of splicing and proportion of highly expressed genes

    PubMed Central

    Trakhtenberg, Ephraim F.; Pho, Nam; Holton, Kristina M.; Chittenden, Thomas W.; Goldberg, Jeffrey L.; Dong, Lingsheng

    2016-01-01

    Balance in the transcriptome is regulated by coordinated synthesis and degradation of RNA molecules. Here we investigated whether mammalian cell types intrinsically differ in global coordination of gene splicing and expression levels. We analyzed RNA-seq transcriptome profiles of 8 different purified mouse cell types. We found that different cell types vary in proportion of highly expressed genes and the number of alternatively spliced transcripts expressed per gene, and that the cell types that express more variants of alternatively spliced transcripts per gene are those that have higher proportion of highly expressed genes. Cell types segregated into two clusters based on high or low proportion of highly expressed genes. Biological functions involved in negative regulation of gene expression were enriched in the group of cell types with low proportion of highly expressed genes, and biological functions involved in regulation of transcription and RNA splicing were enriched in the group of cell types with high proportion of highly expressed genes. Our findings show that cell types differ in proportion of highly expressed genes and the number of alternatively spliced transcripts expressed per gene, which represent distinct properties of the transcriptome and may reflect intrinsic differences in global coordination of synthesis, splicing, and degradation of RNA molecules. PMID:27577089

  4. Mining Metatranscriptomic Data of a Cyanobacterial Bloom for Patterns of Secondary Metabolism Gene Expression

    NASA Astrophysics Data System (ADS)

    Penn, K.; Wang, J.; Thompson, J. R.

    2012-12-01

    The secondary metabolism of bacterial cells produces small molecules that can have both medicinal properties and toxigenic effects. This study focuses on mining metatranscriptomes from a tropical eutrophic water reservoir in Singapore experiencing a cyanobacterial Harmful Algal Bloom dominated by Microcystis, to identify the types of secondary metabolites genes being expressed and by what taxa. A phylogenomic approach as implemented in the online tool Natural Product Domain Seeker (NaPDoS) was used. NaPDoS was recently developed to classify ketosynthase and condensation domains from polyketide synthases and non-ribosomal peptide synthetases, respectively, to provide insight into potential types of pathway products. Water samples from the reservoir were collected six times over a day/night cycle. Total RNA was extracted and subjected to ribosomal depletion followed by cDNA synthesis and next-generation Illumina DNA sequencing, generating 493,468 to 678,064 95-101 base pairs post-quality control reads per sample. Evidence for expression of PKS and NRPS type genes based on identification of a ketosynthase and condensation domains are present in all time points. KS domains fall into to two main phylogenetic groups, type I and type II, within the type II group of domains are domains for fatty acid biosynthesis (fab), which is considered a part of primary metabolism. Type I KS domains are part of the classic PKS natural product biosynthetic genes that make things such as antibiotics and other toxins such as microcystin. 2849 KS domains were detected in the combined reservoir samples, of these 1141 were likely from fatty acid biosynthesis and 1708 were related to secondary metabolism type KS domains. The most abundant KS domains (485) besides the fab genes are closely related to a KS domain that is not currently experimentally linked to a known secondary metabolite but the domain is found in four Microcystis genomes along with two other species of cyanobacteria. The three

  5. Next-generation text-mining mediated generation of chemical response-specific gene sets for interpretation of gene expression data

    PubMed Central

    2013-01-01

    Background Availability of chemical response-specific lists of genes (gene sets) for pharmacological and/or toxic effect prediction for compounds is limited. We hypothesize that more gene sets can be created by next-generation text mining (next-gen TM), and that these can be used with gene set analysis (GSA) methods for chemical treatment identification, for pharmacological mechanism elucidation, and for comparing compound toxicity profiles. Methods We created 30,211 chemical response-specific gene sets for human and mouse by next-gen TM, and derived 1,189 (human) and 588 (mouse) gene sets from the Comparative Toxicogenomics Database (CTD). We tested for significant differential expression (SDE) (false discovery rate -corrected p-values < 0.05) of the next-gen TM-derived gene sets and the CTD-derived gene sets in gene expression (GE) data sets of five chemicals (from experimental models). We tested for SDE of gene sets for six fibrates in a peroxisome proliferator-activated receptor alpha (PPARA) knock-out GE dataset and compared to results from the Connectivity Map. We tested for SDE of 319 next-gen TM-derived gene sets for environmental toxicants in three GE data sets of triazoles, and tested for SDE of 442 gene sets associated with embryonic structures. We compared the gene sets to triazole effects seen in the Whole Embryo Culture (WEC), and used principal component analysis (PCA) to discriminate triazoles from other chemicals. Results Next-gen TM-derived gene sets matching the chemical treatment were significantly altered in three GE data sets, and the corresponding CTD-derived gene sets were significantly altered in five GE data sets. Six next-gen TM-derived and four CTD-derived fibrate gene sets were significantly altered in the PPARA knock-out GE dataset. None of the fibrate signatures in cMap scored significant against the PPARA GE signature. 33 environmental toxicant gene sets were significantly altered in the triazole GE data sets. 21 of these toxicants

  6. Banking biological collections: data warehousing, data mining, and data dilemmas in genomics and global health policy.

    PubMed

    Blatt, R J R

    2000-01-01

    While DNA databases may offer the opportunity to (1) assess population-based prevalence of specific genes and variants, (2) simplify the search for molecular markers, (3) improve targeted drug discovery and development for disease management, (4) refine strategies for disease prevention, and (5) provide the data necessary for evidence-based decision-making, serious scientific and social questions remain. Whether samples are identified, coded, or anonymous, biological banking raises profound ethical and legal issues pertaining to access, informed consent, privacy and confidentiality of genomic information, civil liberties, patenting, and proprietary rights. This paper provides an overview of key policy issues and questions pertaining to biological banking, with a focus on developments in specimen collection, transnational distribution, and public health and academic-industry research alliances. It highlights the challenges posed by the commercialization of genomics, and proposes the need for harmonization of biological banking policies.

  7. Globalization of diabetes: the role of diet, lifestyle, and genes.

    PubMed

    Hu, Frank B

    2011-06-01

    Type 2 diabetes is a global public health crisis that threatens the economies of all nations, particularly developing countries. Fueled by rapid urbanization, nutrition transition, and increasingly sedentary lifestyles, the epidemic has grown in parallel with the worldwide rise in obesity. Asia's large population and rapid economic development have made it an epicenter of the epidemic. Asian populations tend to develop diabetes at younger ages and lower BMI levels than Caucasians. Several factors contribute to accelerated diabetes epidemic in Asians, including the "normal-weight metabolically obese" phenotype; high prevalence of smoking and heavy alcohol use; high intake of refined carbohydrates (e.g., white rice); and dramatically decreased physical activity levels. Poor nutrition in utero and in early life combined with overnutrition in later life may also play a role in Asia's diabetes epidemic. Recent advances in genome-wide association studies have contributed substantially to our understanding of diabetes pathophysiology, but currently identified genetic loci are insufficient to explain ethnic differences in diabetes risk. Nonetheless, interactions between Westernized diet and lifestyle and genetic background may accelerate the growth of diabetes in the context of rapid nutrition transition. Epidemiologic studies and randomized clinical trials show that type 2 diabetes is largely preventable through diet and lifestyle modifications. Translating these findings into practice, however, requires fundamental changes in public policies, the food and built environments, and health systems. To curb the escalating diabetes epidemic, primary prevention through promotion of a healthy diet and lifestyle should be a global public policy priority.

  8. Long term changes of chemical weathering products in rivers heavily impacted from acid mine drainage: Insights on the impact of coal mining on regional and global carbon and sulfur budgets

    NASA Astrophysics Data System (ADS)

    Raymond, Peter A.; Oh, Neung-Hwan

    2009-06-01

    The long term impacts of acid mine drainage (AMD) on stream chemistry and regional carbon and sulfur budgets were explored using watersheds of Pennsylvania underlain by extensive coal deposits. Areas of these watersheds have been mined for 200 yr, yet mining activity decreased to < 2% of peak by the late 1900s. A unique aspect of this study was the coupling of 100 yr of data on stream chemistry measurements with detailed coal mining data, which allowed for new budgets of the impact of mining on regional and global budgets. The Lackawanna River and upper Schuylkill River, both ~ 900 km 2 watersheds, witnessed dramatic changes in pH, alkalinity, calcium, magnesium and sulfate. Sulfate fluxes from these watersheds, for instance, were 4-12 times higher in the 1940s than they are currently. Fluxes of sulfate and magnesium from the Susquehanna River at Danville, the major tributary to the Chesapeake Bay, are currently 32 and 70% of what they were in the 1940s, while alkalinity fluxes have doubled and pH has recovered 0.8 pH units. The direct impact on regional carbon budgets through the degassing of CO 2 from carbonates was intense during the height of AMD but the long term regional impact is modest, resulting in the loss of ~ 3.1 Tg of carbon to the atmosphere over the last century. During the 1940s, the export of AMD derived sulfate to the 29,000 km 2 portion of the Susquehanna River studied here was twice as large as the current input from SO x deposition to the entire 71,000 km 2 Susquehanna watershed. This is surprising, comparing the small spatial footprint of AMD to the large footprint of the entire Susquehanna watershed. Normalizing these export rates to coal production data we estimate that global sulfur releases from AMD could account for 28-40% of riverine sulfate derived from pyrite oxidation, and be equal to ~ 20% of anthropogenic S from atmospheric deposition. This study emphasizes the potential importance of AMD to global S budgets, particularly since coal

  9. Genome mining of the hitachimycin biosynthetic gene cluster: involvement of a phenylalanine-2,3-aminomutase in biosynthesis.

    PubMed

    Kudo, Fumitaka; Kawamura, Koichi; Uchino, Asuka; Miyanaga, Akimasa; Numakura, Mario; Takayanagi, Ryuichi; Eguchi, Tadashi

    2015-04-13

    Hitachimycin is a macrolactam antibiotic with (S)-β-phenylalanine (β-Phe) at the starter position of its polyketide skeleton. To understand the incorporation mechanism of β-Phe and the modification mechanism of the unique polyketide skeleton, the biosynthetic gene cluster for hitachimycin in Streptomyces scabrisporus was identified by genome mining. The identified gene cluster contains a putative phenylalanine-2,3-aminomutase (PAM), five polyketide synthases, four β-amino-acid-carrying enzymes, and a characteristic amidohydrolase. A hitA knockout mutant showed no hitachimycin production, but antibiotic production was restored by feeding with (S)-β-Phe. We also confirmed the enzymatic activity of the HitA PAM. The results suggest that the identified gene cluster is responsible for the biosynthesis of hitachimycin. A plausible biosynthetic pathway for hitachimycin, including a unique polyketide skeletal transformation mechanism, is proposed.

  10. A Spatio-temporal Data Mining Approach to Global scale Burned Area Monitoring

    NASA Astrophysics Data System (ADS)

    Mithal, V.; Khandelwal, A.; Nayak, G.; Kumar, V.; Nemani, R. R.; Oza, N.

    2014-12-01

    We present a novel technique for burned area mapping in forests using the Enhanced Vegetation Index (EVI) from the MODIS 16-day Level 3 1km Vegetation Indices (MOD13A2) and the Active Fire (AF) from the MODIS 8-day Level 3 1km Thermal Anomalies and Fire products (MOD14A2). The proposed method leverages the spatial and temporal co-occurrence of thermal anomalies and vegetation loss caused due to forest fires to detect burned areas. Our approach derives features from Enhanced Vegetation Index that target locations which show an abrupt change in their vegetation time series that take at least several months to recover. One unique aspect of our approach is that it uses data from multiple months around the fire event and is therefore more robust to issues in data quality. Comparison with other burned area products show that our approach detects several large previously undetected burned areas across multiple geographical regions. In particular, we found that our approach detects several large burned regions in the tropical forests of Indonesia and South America that had been missed by the state-of-arts burned area approaches. For example, using our approach in Indonesia we discovered that the state-of-the-art MODIS Burned area product had missed around 20,000 sq. km. of burned area (nearly as much burned area as it has reported). We show that all these previously unreported burned areas detected by our approach are actually significant fires which suffered a large, abrupt loss in their vegetation at the time of the fire event and take at least several months to recover back to their normal vegetation. To evaluate these burned areas we compared the Landsat-based composites before and after the date of the event. Our Landsat analysis shows that the burned areas detected by the proposed approach are true burns with a very small error of commission. We believe our work has the potential to provide a scalable approach to global forest monitoring as well as reduce the

  11. Global identification of target genes regulated by APETALA3 and PISTILLATA floral homeotic gene action.

    PubMed

    Zik, Moriyah; Irish, Vivian F

    2003-01-01

    Identifying the genes regulated by the floral homeotic genes APETALA3 (AP3) and PISTILLATA (PI) is crucial for understanding the molecular mechanisms that lead to petal and stamen formation. We have used microarray analysis to conduct a broad survey of genes whose expression is affected by AP3 and PI activity. DNA microarrays consisting of 9216 Arabidopsis ESTs were screened with probes corresponding to mRNAs from different mutant and transgenic lines that misexpress AP3 and/or PI. The microarray results were further confirmed by RNA gel blot analyses. Our results suggest that AP3 and PI regulate a relatively small number of genes, implying that many genes used in petal and stamen development are not tissue specific and likely have roles in other processes as well. We recovered genes similar to previously identified petal- and stamen-expressed genes as well as genes that were not implicated previously in petal and stamen development. A very low percentage of the genes recovered encoded transcription factors. This finding suggests that AP3 and PI act relatively directly to regulate the genes required for the basic cellular processes responsible for petal and stamen morphogenesis.

  12. GE-Miner: integration of cluster ensemble and text mining for comprehensive gene expression analysis.

    PubMed

    Hu, Xiaohua

    2006-01-01

    Generating high quality gene clusters and identifying the underlying biological mechanism of the gene clusters are the important goals of clustering gene expression analysis. Based on this consideration, we design and develop a unified system Gene Expression Miner (GE-Miner) by integrating cluster ensemble, text clustering and multidocument summarisation and provide an environment for comprehensive gene expression data analysis. Experimental results demonstrate that our systems can obtain high quality clusters and provide concise and informative textual summary for the gene clusters.

  13. Mobile genes in the human microbiome are structured from global to individual scales.

    PubMed

    Brito, I L; Yilmaz, S; Huang, K; Xu, L; Jupiter, S D; Jenkins, A P; Naisilisili, W; Tamminen, M; Smillie, C S; Wortman, J R; Birren, B W; Xavier, R J; Blainey, P C; Singh, A K; Gevers, D; Alm, E J

    2016-07-21

    Recent work has underscored the importance of the microbiome in human health, and has largely attributed differences in phenotype to differences in the species present among individuals. However, mobile genes can confer profoundly different phenotypes on different strains of the same species. Little is known about the function and distribution of mobile genes in the human microbiome, and in particular whether the gene pool is globally homogenous or constrained by human population structure. Here, we investigate this question by comparing the mobile genes found in the microbiomes of 81 metropolitan North Americans with those of 172 agrarian Fiji islanders using a combination of single-cell genomics and metagenomics. We find large differences in mobile gene content between the Fijian and North American microbiomes, with functional variation that mirrors known dietary differences such as the excess of plant-based starch degradation genes found in Fijian individuals. Notably, we also observed differences between the mobile gene pools of neighbouring Fijian villages, even though microbiome composition across villages is similar. Finally, we observe high rates of recombination leading to individual-specific mobile elements, suggesting that the abundance of some genes may reflect environmental selection rather than dispersal limitation. Together, these data support the hypothesis that human activities and behaviours provide selective pressures that shape mobile gene pools, and that acquisition of mobile genes is important for colonizing specific human populations. PMID:27409808

  14. The facilitating roles and uses of gene banks in addressing the global plan of action

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Contractions of livestock genetic resources are occurring as countries strive to meet increasing demand for livestock products. The Global Plan of Action’s (GPA) Strategic Priority Area 3 – Conservation, calls for governments to establish gene banks for ex-situ cryogenic conservation. Establishment ...

  15. Benzo[a]pyrene decreases global and gene specific DNA methylation during zebrafish development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    DNA methylation is important for gene regulation and is vulnerable to early-life exposure to environmental contaminants. We found that direct waterborne benzo[a]pyrene (BaP) exposure at 24 'g/L from 2.5 to 96 hours post fertilization (hpf) to zebrafish embryos significantly decreased global cytosine...

  16. Global transcription network incorporating distal regulator binding reveals selective cooperation of cancer drivers and risk genes

    PubMed Central

    Kim, Kwoneel; Yang, Woojin; Lee, Kang Seon; Bang, Hyoeun; Jang, Kiwon; Kim, Sang Cheol; Yang, Jin Ok; Park, Seongjin; Park, Kiejung; Choi, Jung Kyoon

    2015-01-01

    Global network modeling of distal regulatory interactions is essential in understanding the overall architecture of gene expression programs. Here, we developed a Bayesian probabilistic model and computational method for global causal network construction with breast cancer as a model. Whereas physical regulator binding was well supported by gene expression causality in general, distal elements in intragenic regions or loci distant from the target gene exhibited particularly strong functional effects. Modeling the action of long-range enhancers was critical in recovering true biological interactions with increased coverage and specificity overall and unraveling regulatory complexity underlying tumor subclasses and drug responses in particular. Transcriptional cancer drivers and risk genes were discovered based on the network analysis of somatic and genetic cancer-related DNA variants. Notably, we observed that the risk genes were functionally downstream of the cancer drivers and were selectively susceptible to network perturbation by tumorigenic changes in their upstream drivers. Furthermore, cancer risk alleles tended to increase the susceptibility of the transcription of their associated genes. These findings suggest that transcriptional cancer drivers selectively induce a combinatorial misregulation of downstream risk genes, and that genetic risk factors, mostly residing in distal regulatory regions, increase transcriptional susceptibility to upstream cancer-driving somatic changes. PMID:26001967

  17. Krylov subspace algorithms for computing GeneRank for the analysis of microarray data mining.

    PubMed

    Wu, Gang; Zhang, Ying; Wei, Yimin

    2010-04-01

    GeneRank is a new engine technology for the analysis of microarray experiments. It combines gene expression information with a network structure derived from gene notations or expression profile correlations. Using matrix decomposition techniques, we first give a matrix analysis of the GeneRank model. We reformulate the GeneRank vector as a linear combination of three parts in the general case when the matrix in question is non-diagonalizable. We then propose two Krylov subspace methods for computing GeneRank. Numerical experiments show that, when the GeneRank problem is very large, the new algorithms are appropriate choices. PMID:20426695

  18. The harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins.

    PubMed

    Rouillard, Andrew D; Gundersen, Gregory W; Fernandez, Nicolas F; Wang, Zichen; Monteiro, Caroline D; McDermott, Michael G; Ma'ayan, Avi

    2016-01-01

    Genomics, epigenomics, transcriptomics, proteomics and metabolomics efforts rapidly generate a plethora of data on the activity and levels of biomolecules within mammalian cells. At the same time, curation projects that organize knowledge from the biomedical literature into online databases are expanding. Hence, there is a wealth of information about genes, proteins and their associations, with an urgent need for data integration to achieve better knowledge extraction and data reuse. For this purpose, we developed the Harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins from over 70 major online resources. We extracted, abstracted and organized data into ∼72 million functional associations between genes/proteins and their attributes. Such attributes could be physical relationships with other biomolecules, expression in cell lines and tissues, genetic associations with knockout mouse or human phenotypes, or changes in expression after drug treatment. We stored these associations in a relational database along with rich metadata for the genes/proteins, their attributes and the original resources. The freely available Harmonizome web portal provides a graphical user interface, a web service and a mobile app for querying, browsing and downloading all of the collected data. To demonstrate the utility of the Harmonizome, we computed and visualized gene-gene and attribute-attribute similarity networks, and through unsupervised clustering, identified many unexpected relationships by combining pairs of datasets such as the association between kinase perturbations and disease signatures. We also applied supervised machine learning methods to predict novel substrates for kinases, endogenous ligands for G-protein coupled receptors, mouse phenotypes for knockout genes, and classified unannotated transmembrane proteins for likelihood of being ion channels. The Harmonizome is a comprehensive resource of knowledge about

  19. Global gene expression profiles reveal significant nuclear reprogramming by the blastocyst stage after cloning.

    PubMed

    Smith, Sadie L; Everts, Robin E; Tian, X Cindy; Du, Fuliang; Sung, Li-Ying; Rodriguez-Zas, Sandra L; Jeong, Byeong-Seon; Renard, Jean-Paul; Lewin, Harris A; Yang, Xiangzhong

    2005-12-01

    Nuclear transfer (NT) has potential applications in agriculture and biomedicine, but the technology is hindered by low efficiency. Global gene expression analysis of clones is important for the comprehensive study of nuclear reprogramming. Here, we compared global gene expression profiles of individual bovine NT blastocysts with their somatic donor cells and fertilized control embryos using cDNA microarray technology. The NT embryos' gene expression profiles were drastically different from those of their donor cells and closely resembled those of the naturally fertilized embryos. Our findings demonstrate that the NT embryos have undergone significant nuclear reprogramming by the blastocyst stage; however, problems may occur during redifferentiation for tissue genesis and organogenesis, and small reprogramming errors may be magnified downstream in development.

  20. Global Landscape of a Co-Expressed Gene Network in Barley and its Application to Gene Discovery in Triticeae Crops

    PubMed Central

    Mochida, Keiichi; Uehara-Yamaguchi, Yukiko; Yoshida, Takuhiro; Sakurai, Tetsuya; Shinozaki, Kazuo

    2011-01-01

    Accumulated transcriptome data can be used to investigate regulatory networks of genes involved in various biological systems. Co-expression analysis data sets generated from comprehensively collected transcriptome data sets now represent efficient resources that are capable of facilitating the discovery of genes with closely correlated expression patterns. In order to construct a co-expression network for barley, we analyzed 45 publicly available experimental series, which are composed of 1,347 sets of GeneChip data for barley. On the basis of a gene-to-gene weighted correlation coefficient, we constructed a global barley co-expression network and classified it into clusters of subnetwork modules. The resulting clusters are candidates for functional regulatory modules in the barley transcriptome. To annotate each of the modules, we performed comparative annotation using genes in Arabidopsis and Brachypodium distachyon. On the basis of a comparative analysis between barley and two model species, we investigated functional properties from the representative distributions of the gene ontology (GO) terms. Modules putatively involved in drought stress response and cellulose biogenesis have been identified. These modules are discussed to demonstrate the effectiveness of the co-expression analysis. Furthermore, we applied the data set of co-expressed genes coupled with comparative analysis in attempts to discover potentially Triticeae-specific network modules. These results demonstrate that analysis of the co-expression network of the barley transcriptome together with comparative analysis should promote the process of gene discovery in barley. Furthermore, the insights obtained should be transferable to investigations of Triticeae plants. The associated data set generated in this analysis is publicly accessible at http://coexpression.psc.riken.jp/barley/. PMID:21441235

  1. The harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins

    PubMed Central

    Rouillard, Andrew D.; Gundersen, Gregory W.; Fernandez, Nicolas F.; Wang, Zichen; Monteiro, Caroline D.; McDermott, Michael G.; Ma’ayan, Avi

    2016-01-01

    Genomics, epigenomics, transcriptomics, proteomics and metabolomics efforts rapidly generate a plethora of data on the activity and levels of biomolecules within mammalian cells. At the same time, curation projects that organize knowledge from the biomedical literature into online databases are expanding. Hence, there is a wealth of information about genes, proteins and their associations, with an urgent need for data integration to achieve better knowledge extraction and data reuse. For this purpose, we developed the Harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins from over 70 major online resources. We extracted, abstracted and organized data into ∼72 million functional associations between genes/proteins and their attributes. Such attributes could be physical relationships with other biomolecules, expression in cell lines and tissues, genetic associations with knockout mouse or human phenotypes, or changes in expression after drug treatment. We stored these associations in a relational database along with rich metadata for the genes/proteins, their attributes and the original resources. The freely available Harmonizome web portal provides a graphical user interface, a web service and a mobile app for querying, browsing and downloading all of the collected data. To demonstrate the utility of the Harmonizome, we computed and visualized gene–gene and attribute–attribute similarity networks, and through unsupervised clustering, identified many unexpected relationships by combining pairs of datasets such as the association between kinase perturbations and disease signatures. We also applied supervised machine learning methods to predict novel substrates for kinases, endogenous ligands for G-protein coupled receptors, mouse phenotypes for knockout genes, and classified unannotated transmembrane proteins for likelihood of being ion channels. The Harmonizome is a comprehensive resource of knowledge

  2. Mining Gene Expression Data for Pollutants (Dioxin, Toluene, Formaldehyde) and Low Dose of Gamma-Irradiation

    PubMed Central

    Moskalev, Alexey; Shaposhnikov, Mikhail; Snezhkina, Anastasia; Kogan, Valeria; Plyusnina, Ekaterina; Peregudova, Darya; Melnikova, Nataliya; Uroshlev, Leonid; Mylnikov, Sergey; Dmitriev, Alexey; Plusnin, Sergey; Fedichev, Peter; Kudryavtseva, Anna

    2014-01-01

    General and specific effects of molecular genetic responses to adverse environmental factors are not well understood. This study examines genome-wide gene expression profiles of Drosophila melanogaster in response to ionizing radiation, formaldehyde, toluene, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. We performed RNA-seq analysis on 25,415 transcripts to measure the change in gene expression in males and females separately. An analysis of the genes unique to each treatment yielded a list of genes as a gene expression signature. In the case of radiation exposure, both sexes exhibited a reproducible increase in their expression of the transcription factors sugarbabe and tramtrack. The influence of dioxin up-regulated metabolic genes, such as anachronism, CG16727, and several genes with unknown function. Toluene activated a gene involved in the response to the toxins, Cyp12d1-p; the transcription factor Fer3’s gene; the metabolic genes CG2065, CG30427, and CG34447; and the genes Spn28Da and Spn3, which are responsible for reproduction and immunity. All significantly differentially expressed genes, including those shared among the stressors, can be divided into gene groups using Gene Ontology Biological Process identifiers. These gene groups are related to defense response, biological regulation, the cell cycle, metabolic process, and circadian rhythms. KEGG molecular pathway analysis revealed alteration of the Notch signaling pathway, TGF-beta signaling pathway, proteasome, basal transcription factors, nucleotide excision repair, Jak-STAT signaling pathway, circadian rhythm, Hippo signaling pathway, mTOR signaling pathway, ribosome, mismatch repair, RNA polymerase, mRNA surveillance pathway, Hedgehog signaling pathway, and DNA replication genes. Females and, to a lesser extent, males actively metabolize xenobiotics by the action of cytochrome P450 when under the influence of dioxin and toluene. Finally, in this work we obtained gene expression signatures pollutants

  3. Mining gene expression data for pollutants (dioxin, toluene, formaldehyde) and low dose of gamma-irradiation.

    PubMed

    Moskalev, Alexey; Shaposhnikov, Mikhail; Snezhkina, Anastasia; Kogan, Valeria; Plyusnina, Ekaterina; Peregudova, Darya; Melnikova, Nataliya; Uroshlev, Leonid; Mylnikov, Sergey; Dmitriev, Alexey; Plusnin, Sergey; Fedichev, Peter; Kudryavtseva, Anna

    2014-01-01

    General and specific effects of molecular genetic responses to adverse environmental factors are not well understood. This study examines genome-wide gene expression profiles of Drosophila melanogaster in response to ionizing radiation, formaldehyde, toluene, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. We performed RNA-seq analysis on 25,415 transcripts to measure the change in gene expression in males and females separately. An analysis of the genes unique to each treatment yielded a list of genes as a gene expression signature. In the case of radiation exposure, both sexes exhibited a reproducible increase in their expression of the transcription factors sugarbabe and tramtrack. The influence of dioxin up-regulated metabolic genes, such as anachronism, CG16727, and several genes with unknown function. Toluene activated a gene involved in the response to the toxins, Cyp12d1-p; the transcription factor Fer3's gene; the metabolic genes CG2065, CG30427, and CG34447; and the genes Spn28Da and Spn3, which are responsible for reproduction and immunity. All significantly differentially expressed genes, including those shared among the stressors, can be divided into gene groups using Gene Ontology Biological Process identifiers. These gene groups are related to defense response, biological regulation, the cell cycle, metabolic process, and circadian rhythms. KEGG molecular pathway analysis revealed alteration of the Notch signaling pathway, TGF-beta signaling pathway, proteasome, basal transcription factors, nucleotide excision repair, Jak-STAT signaling pathway, circadian rhythm, Hippo signaling pathway, mTOR signaling pathway, ribosome, mismatch repair, RNA polymerase, mRNA surveillance pathway, Hedgehog signaling pathway, and DNA replication genes. Females and, to a lesser extent, males actively metabolize xenobiotics by the action of cytochrome P450 when under the influence of dioxin and toluene. Finally, in this work we obtained gene expression signatures pollutants

  4. Global variability in gene expression and alternative splicing is modulated by mitochondrial content.

    PubMed

    Guantes, Raul; Rastrojo, Alberto; Neves, Ricardo; Lima, Ana; Aguado, Begoña; Iborra, Francisco J

    2015-05-01

    Noise in gene expression is a main determinant of phenotypic variability. Increasing experimental evidence suggests that genome-wide cellular constraints largely contribute to the heterogeneity observed in gene products. It is still unclear, however, which global factors affect gene expression noise and to what extent. Since eukaryotic gene expression is an energy demanding process, differences in the energy budget of each cell could determine gene expression differences. Here, we quantify the contribution of mitochondrial variability (a natural source of ATP variation) to global variability in gene expression. We find that changes in mitochondrial content can account for ∼50% of the variability observed in protein levels. This is the combined result of the effect of mitochondria dosage on transcription and translation apparatus content and activities. Moreover, we find that mitochondrial levels have a large impact on alternative splicing, thus modulating both the abundance and type of mRNAs. A simple mathematical model in which mitochondrial content simultaneously affects transcription rate and splicing site choice can explain the alternative splicing data. The results of this study show that mitochondrial content (and/or probably function) influences mRNA abundance, translation, and alternative splicing, which ultimately affects cellular phenotype.

  5. Global variability in gene expression and alternative splicing is modulated by mitochondrial content

    PubMed Central

    Guantes, Raul; Rastrojo, Alberto; Neves, Ricardo; Lima, Ana; Aguado, Begoña; Iborra, Francisco J.

    2015-01-01

    Noise in gene expression is a main determinant of phenotypic variability. Increasing experimental evidence suggests that genome-wide cellular constraints largely contribute to the heterogeneity observed in gene products. It is still unclear, however, which global factors affect gene expression noise and to what extent. Since eukaryotic gene expression is an energy demanding process, differences in the energy budget of each cell could determine gene expression differences. Here, we quantify the contribution of mitochondrial variability (a natural source of ATP variation) to global variability in gene expression. We find that changes in mitochondrial content can account for ∼50% of the variability observed in protein levels. This is the combined result of the effect of mitochondria dosage on transcription and translation apparatus content and activities. Moreover, we find that mitochondrial levels have a large impact on alternative splicing, thus modulating both the abundance and type of mRNAs. A simple mathematical model in which mitochondrial content simultaneously affects transcription rate and splicing site choice can explain the alternative splicing data. The results of this study show that mitochondrial content (and/or probably function) influences mRNA abundance, translation, and alternative splicing, which ultimately affects cellular phenotype. PMID:25800673

  6. Global variability in gene expression and alternative splicing is modulated by mitochondrial content.

    PubMed

    Guantes, Raul; Rastrojo, Alberto; Neves, Ricardo; Lima, Ana; Aguado, Begoña; Iborra, Francisco J

    2015-05-01

    Noise in gene expression is a main determinant of phenotypic variability. Increasing experimental evidence suggests that genome-wide cellular constraints largely contribute to the heterogeneity observed in gene products. It is still unclear, however, which global factors affect gene expression noise and to what extent. Since eukaryotic gene expression is an energy demanding process, differences in the energy budget of each cell could determine gene expression differences. Here, we quantify the contribution of mitochondrial variability (a natural source of ATP variation) to global variability in gene expression. We find that changes in mitochondrial content can account for ∼50% of the variability observed in protein levels. This is the combined result of the effect of mitochondria dosage on transcription and translation apparatus content and activities. Moreover, we find that mitochondrial levels have a large impact on alternative splicing, thus modulating both the abundance and type of mRNAs. A simple mathematical model in which mitochondrial content simultaneously affects transcription rate and splicing site choice can explain the alternative splicing data. The results of this study show that mitochondrial content (and/or probably function) influences mRNA abundance, translation, and alternative splicing, which ultimately affects cellular phenotype. PMID:25800673

  7. Global effects on gene expression in fission yeast by silencing and RNA interference machineries.

    PubMed

    Hansen, Klavs R; Burns, Gavin; Mata, Juan; Volpe, Thomas A; Martienssen, Robert A; Bähler, Jürg; Thon, Geneviève

    2005-01-01

    Histone modifications influence gene expression in complex ways. The RNA interference (RNAi) machinery can repress transcription by recruiting histone-modifying enzymes to chromatin, although it is not clear whether this is a general mechanism for gene silencing or whether it requires repeated sequences such as long terminal repeats (LTRs). We analyzed the global effects of the Clr3 and Clr6 histone deacetylases, the Clr4 methyltransferase, the zinc finger protein Clr1, and the RNAi proteins Dicer, RdRP, and Argonaute on the transcriptome of Schizosaccharomyces pombe (fission yeast). The clr mutants derepressed similar subsets of genes, many of which also became transcriptionally activated in cells that were exposed to environmental stresses such as nitrogen starvation. Many genes that were repressed by the Clr proteins clustered in extended regions close to the telomeres. Surprisingly few genes were repressed by both the silencing and RNAi machineries, with transcripts from centromeric repeats and Tf2 retrotransposons being notable exceptions. We found no correlation between repression by RNAi and proximity to LTRs, and the wtf family of repeated sequences seems to be repressed by histone deacetylation independent of RNAi. Our data indicate that the RNAi and Clr proteins show only a limited functional overlap and that the Clr proteins play more global roles in gene silencing. PMID:15632061

  8. Global Regulation of Gene Expression by the MafR Protein of Enterococcus faecalis

    PubMed Central

    Ruiz-Cruz, Sofía; Espinosa, Manuel; Goldmann, Oliver; Bravo, Alicia

    2016-01-01

    Enterococcus faecalis is a natural inhabitant of the human gastrointestinal tract. However, as an opportunistic pathogen, it is able to colonize other host niches and cause life-threatening infections. Its adaptation to new environments involves global changes in gene expression. The EF3013 gene (here named mafR) of E. faecalis strain V583 encodes a protein (MafR, 482 residues) that has sequence similarity to global response regulators of the Mga/AtxA family. The enterococcal OG1RF genome also encodes the MafR protein (gene OG1RF_12293). In this work, we have identified the promoter of the mafR gene using several in vivo approaches. Moreover, we show that MafR influences positively the transcription of many genes on a genome-wide scale. The most significant target genes encode components of PTS-type membrane transporters, components of ABC-type membrane transporters, and proteins involved in the metabolism of carbon sources. Some of these genes were previously reported to be up-regulated during the growth of E. faecalis in blood and/or in human urine. Furthermore, we show that a mafR deletion mutant strain induces a significant lower degree of inflammation in the peritoneal cavity of mice, suggesting that enterococcal cells deficient in MafR are less virulent. Our work indicates that MafR is a global transcriptional regulator. It might facilitate the adaptation of E. faecalis to particular host niches and, therefore, contribute to its potential virulence. PMID:26793169

  9. Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

    NASA Technical Reports Server (NTRS)

    Yeshitla, Samrawit A.; Lam, Chiu-Wing; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Wu, Honglu; James, John T.; Meyers, Valerie E.; Zhang, Ye

    2014-01-01

    The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1-2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose-dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.

  10. Global gene expression of Poncirus trifoliata, Citrus sunki and their hybrids under infection of Phytophthora parasitica

    PubMed Central

    2011-01-01

    Background Gummosis and root rot caused by Phytophthora are among the most economically important diseases in citrus. Four F1 resistant hybrids (Pool R), and four F1 susceptible hybrids (Pool S) to P. parasitica, were selected from a cross between susceptible Citrus sunki and resistant Poncirus trifoliata cv. Rubidoux. We investigated gene expression in pools of four resistant and four susceptible hybrids in comparison with their parents 48 hours after P. parasitica inoculation. We proposed that genes differentially expressed between resistant and susceptible parents and between their resistant and susceptible hybrids provide promising candidates for identifying transcripts involved in disease resistance. A microarray containing 62,876 UniGene transcripts selected from the CitEST database and prepared by NimbleGen Systems was used for analyzing global gene expression 48 hours after infection with P. parasitica. Results Three pairs of data comparisons (P. trifoliata/C. sunki, Pool R/C. sunki and Pool R/Pool S) were performed. With a filter of false-discovery rate less than 0.05 and fold change greater than 3.0, 21 UniGene transcripts common to the three pairwise comparative were found to be up-regulated, and 3 UniGene transcripts were down-regulated. Among them, our results indicated that the selected transcripts were probably involved in the whole process of plant defense responses to pathogen attack, including transcriptional regulation, signaling, activation of defense genes participating in HR, single dominant genes (R gene) such as TIR-NBS-LRR and RPS4 and switch of defense-related metabolism pathway. Differentially expressed genes were validated by RT-qPCR in susceptible and resistant plants and between inoculated and uninoculated control plants Conclusions Twenty four UniGene transcripts were identified as candidate genes for Citrus response to P. parasitica. UniGene transcripts were likely to be involved in disease resistance, such as genes potentially

  11. Expression analysis of global gene response to chronic heat exposure in broiler chickens (Gallus gallus) reveals new reactive genes.

    PubMed

    Li, C; Wang, X; Wang, G; Li, N; Wu, C

    2011-05-01

    The process of heat regulation is complex and the exact molecular mechanism is not fully understood. To investigate the global gene response to chronic heat exposure, a breast muscle cDNA library and a liver tissue cDNA library from Silkie fowl were constructed and analyzed in bioinformatics. A total of 8,935 nonredundant EST were identified from and used for gene expression analysis. Microarray assay revealed that in breast muscle of broiler chickens (Gallus gallus), 110 genes changed expression levels after 3 wk of cycling heat stress. Ubiquitin B (UBB); ubiquitin C (UBC); tumor necrosis factor receptor-associated factor 3-interacting Jun amino-terminal kinase activating modulator (TRAF3IP3); eukaryotic translation initiation factor 3, subunit 6 (EIF3S6); poly(A) binding protein, cytoplasmic 1 (PABPC1); and F-box only protein 11 (FBXO11) were the only genes that have been reported to be involved in heat regulation; the majority of the other genes were shown to be related for the first time. The finding of new heat-reactive genes [mitogen-activated protein kinase activating protein PM20/PM21; suppressors of cytokine signaling (SOCS) box-containing protein 2 (ASB2); ubiquitin-specific proteinase 45 (USP45); and TRK-fused gene (TFG)] suggests that the mitogen-activated protein kinase pathways as well as the ubiquitin-proteasome pathways and the nuclear factor κB pathways play important roles in heat regulation. This study provides new information on the regulation of heat stress, though the mechanism is far from being understood. Further in-depth research on the newly discovered heat-reactive genes is required to fully understand their molecular functions in thermoregulation.

  12. Molecular networking and pattern-based genome mining improves discovery of biosynthetic gene clusters and their products from Salinispora species.

    PubMed

    Duncan, Katherine R; Crüsemann, Max; Lechner, Anna; Sarkar, Anindita; Li, Jie; Ziemert, Nadine; Wang, Mingxun; Bandeira, Nuno; Moore, Bradley S; Dorrestein, Pieter C; Jensen, Paul R

    2015-04-23

    Genome sequencing has revealed that bacteria contain many more biosynthetic gene clusters than predicted based on the number of secondary metabolites discovered to date. While this biosynthetic reservoir has fostered interest in new tools for natural product discovery, there remains a gap between gene cluster detection and compound discovery. Here we apply molecular networking and the new concept of pattern-based genome mining to 35 Salinispora strains, including 30 for which draft genome sequences were either available or obtained for this study. The results provide a method to simultaneously compare large numbers of complex microbial extracts, which facilitated the identification of media components, known compounds and their derivatives, and new compounds that could be prioritized for structure elucidation. These efforts revealed considerable metabolite diversity and led to several molecular family-gene cluster pairings, of which the quinomycin-type depsipeptide retimycin A was characterized and linked to gene cluster NRPS40 using pattern-based bioinformatic approaches.

  13. antiSMASH 3.0-a comprehensive resource for the genome mining of biosynthetic gene clusters.

    PubMed

    Weber, Tilmann; Blin, Kai; Duddela, Srikanth; Krug, Daniel; Kim, Hyun Uk; Bruccoleri, Robert; Lee, Sang Yup; Fischbach, Michael A; Müller, Rolf; Wohlleben, Wolfgang; Breitling, Rainer; Takano, Eriko; Medema, Marnix H

    2015-07-01

    Microbial secondary metabolism constitutes a rich source of antibiotics, chemotherapeutics, insecticides and other high-value chemicals. Genome mining of gene clusters that encode the biosynthetic pathways for these metabolites has become a key methodology for novel compound discovery. In 2011, we introduced antiSMASH, a web server and stand-alone tool for the automatic genomic identification and analysis of biosynthetic gene clusters, available at http://antismash.secondarymetabolites.org. Here, we present version 3.0 of antiSMASH, which has undergone major improvements. A full integration of the recently published ClusterFinder algorithm now allows using this probabilistic algorithm to detect putative gene clusters of unknown types. Also, a new dereplication variant of the ClusterBlast module now identifies similarities of identified clusters to any of 1172 clusters with known end products. At the enzyme level, active sites of key biosynthetic enzymes are now pinpointed through a curated pattern-matching procedure and Enzyme Commission numbers are assigned to functionally classify all enzyme-coding genes. Additionally, chemical structure prediction has been improved by incorporating polyketide reduction states. Finally, in order for users to be able to organize and analyze multiple antiSMASH outputs in a private setting, a new XML output module allows offline editing of antiSMASH annotations within the Geneious software.

  14. SSH gene expression profile of Eisenia andrei exposed in situ to a naturally contaminated soil from an abandoned uranium mine.

    PubMed

    Lourenço, Joana; Pereira, Ruth; Gonçalves, Fernando; Mendo, Sónia

    2013-02-01

    The effects of the exposure of earthworms (Eisenia andrei) to contaminated soil from an abandoned uranium mine, were assessed through gene expression profile evaluation by Suppression Subtractive Hybridization (SSH). Organisms were exposed in situ for 56 days, in containers placed both in a contaminated and in a non-contaminated site (reference). Organisms were sampled after 14 and 56 days of exposure. Results showed that the main physiological functions affected by the exposure to metals and radionuclides were: metabolism, oxireductase activity, redox homeostasis and response to chemical stimulus and stress. The relative expression of NADH dehydrogenase subunit 1 and elongation factor 1 alpha was also affected, since the genes encoding these enzymes were significantly up and down-regulated, after 14 and 56 days of exposure, respectively. Also, an EST with homology for SET oncogene was found to be up-regulated. To the best of our knowledge, this is the first time that this gene was identified in earthworms and thus, further studies are required, to clarify its involvement in the toxicity of metals and radionuclides. Considering the results herein presented, gene expression profiling proved to be a very useful tool to detect earthworms underlying responses to metals and radionuclides exposure, pointing out for the detection and development of potential new biomarkers.

  15. Expression Analysis of Ni- and V-Associated Resistance Genes in a Bacillus megaterium Strain Isolated from a Mining Site.

    PubMed

    Fierros Romero, Grisel; Rivas Castillo, Andrea; Gómez Ramírez, Marlenne; Pless, Reynaldo; Rojas Avelizapa, Norma

    2016-08-01

    Bacillus megaterium strain MNSH1-9K-1 was isolated from a mining site in Guanajuato, Mexico. This B. megaterium strain presented the ability to remove Ni and V from a spent catalyst. Also, its associated metal resistance genes nccA, hant, VAN2, and smtAB were previously identified by a PCR approach. The present study reports for the first time, in B. megaterium, the changes in the expression of the genes nccA (Ni-Co-Cd resistance); hant (high-affinity nickel transporter); smtAB, a metal-binding protein gene; and VAN2 (V resistance) after exposure to 200 ppm of Ni and 200 ppm of V during the stationary phase of the microorganism in PHGII liquid media. The data presented here may contribute to the knowledge of the genes involved in the Ni and V resistances of B. megaterium, and the possible pathways implicated in the Ni-V removal processes, which may be potentiated for the biological treatment of high metal content residues.

  16. Global Gene-Expression Analysis to Identify Differentially Expressed Genes Critical for the Heat Stress Response in Brassica rapa

    PubMed Central

    Dong, Xiangshu; Yi, Hankuil; Lee, Jeongyeo; Nou, Ill-Sup; Han, Ching-Tack; Hur, Yoonkang

    2015-01-01

    Genome-wide dissection of the heat stress response (HSR) is necessary to overcome problems in crop production caused by global warming. To identify HSR genes, we profiled gene expression in two Chinese cabbage inbred lines with different thermotolerances, Chiifu and Kenshin. Many genes exhibited >2-fold changes in expression upon exposure to 0.5– 4 h at 45°C (high temperature, HT): 5.2% (2,142 genes) in Chiifu and 3.7% (1,535 genes) in Kenshin. The most enriched GO (Gene Ontology) items included ‘response to heat’, ‘response to reactive oxygen species (ROS)’, ‘response to temperature stimulus’, ‘response to abiotic stimulus’, and ‘MAPKKK cascade’. In both lines, the genes most highly induced by HT encoded small heat shock proteins (Hsps) and heat shock factor (Hsf)-like proteins such as HsfB2A (Bra029292), whereas high-molecular weight Hsps were constitutively expressed. Other upstream HSR components were also up-regulated: ROS-scavenging genes like glutathione peroxidase 2 (BrGPX2, Bra022853), protein kinases, and phosphatases. Among heat stress (HS) marker genes in Arabidopsis, only exportin 1A (XPO1A) (Bra008580, Bra006382) can be applied to B. rapa for basal thermotolerance (BT) and short-term acquired thermotolerance (SAT) gene. CYP707A3 (Bra025083, Bra021965), which is involved in the dehydration response in Arabidopsis, was associated with membrane leakage in both lines following HS. Although many transcription factors (TF) genes, including DREB2A (Bra005852), were involved in HS tolerance in both lines, Bra024224 (MYB41) and Bra021735 (a bZIP/AIR1 [Anthocyanin-Impaired-Response-1]) were specific to Kenshin. Several candidate TFs involved in thermotolerance were confirmed as HSR genes by real-time PCR, and these assignments were further supported by promoter analysis. Although some of our findings are similar to those obtained using other plant species, clear differences in Brassica rapa reveal a distinct HSR in this species. Our data

  17. Global Gene-Expression Analysis to Identify Differentially Expressed Genes Critical for the Heat Stress Response in Brassica rapa.

    PubMed

    Dong, Xiangshu; Yi, Hankuil; Lee, Jeongyeo; Nou, Ill-Sup; Han, Ching-Tack; Hur, Yoonkang

    2015-01-01

    Genome-wide dissection of the heat stress response (HSR) is necessary to overcome problems in crop production caused by global warming. To identify HSR genes, we profiled gene expression in two Chinese cabbage inbred lines with different thermotolerances, Chiifu and Kenshin. Many genes exhibited >2-fold changes in expression upon exposure to 0.5- 4 h at 45°C (high temperature, HT): 5.2% (2,142 genes) in Chiifu and 3.7% (1,535 genes) in Kenshin. The most enriched GO (Gene Ontology) items included 'response to heat', 'response to reactive oxygen species (ROS)', 'response to temperature stimulus', 'response to abiotic stimulus', and 'MAPKKK cascade'. In both lines, the genes most highly induced by HT encoded small heat shock proteins (Hsps) and heat shock factor (Hsf)-like proteins such as HsfB2A (Bra029292), whereas high-molecular weight Hsps were constitutively expressed. Other upstream HSR components were also up-regulated: ROS-scavenging genes like glutathione peroxidase 2 (BrGPX2, Bra022853), protein kinases, and phosphatases. Among heat stress (HS) marker genes in Arabidopsis, only exportin 1A (XPO1A) (Bra008580, Bra006382) can be applied to B. rapa for basal thermotolerance (BT) and short-term acquired thermotolerance (SAT) gene. CYP707A3 (Bra025083, Bra021965), which is involved in the dehydration response in Arabidopsis, was associated with membrane leakage in both lines following HS. Although many transcription factors (TF) genes, including DREB2A (Bra005852), were involved in HS tolerance in both lines, Bra024224 (MYB41) and Bra021735 (a bZIP/AIR1 [Anthocyanin-Impaired-Response-1]) were specific to Kenshin. Several candidate TFs involved in thermotolerance were confirmed as HSR genes by real-time PCR, and these assignments were further supported by promoter analysis. Although some of our findings are similar to those obtained using other plant species, clear differences in Brassica rapa reveal a distinct HSR in this species. Our data could also provide a

  18. Global Gene-Expression Analysis to Identify Differentially Expressed Genes Critical for the Heat Stress Response in Brassica rapa.

    PubMed

    Dong, Xiangshu; Yi, Hankuil; Lee, Jeongyeo; Nou, Ill-Sup; Han, Ching-Tack; Hur, Yoonkang

    2015-01-01

    Genome-wide dissection of the heat stress response (HSR) is necessary to overcome problems in crop production caused by global warming. To identify HSR genes, we profiled gene expression in two Chinese cabbage inbred lines with different thermotolerances, Chiifu and Kenshin. Many genes exhibited >2-fold changes in expression upon exposure to 0.5- 4 h at 45°C (high temperature, HT): 5.2% (2,142 genes) in Chiifu and 3.7% (1,535 genes) in Kenshin. The most enriched GO (Gene Ontology) items included 'response to heat', 'response to reactive oxygen species (ROS)', 'response to temperature stimulus', 'response to abiotic stimulus', and 'MAPKKK cascade'. In both lines, the genes most highly induced by HT encoded small heat shock proteins (Hsps) and heat shock factor (Hsf)-like proteins such as HsfB2A (Bra029292), whereas high-molecular weight Hsps were constitutively expressed. Other upstream HSR components were also up-regulated: ROS-scavenging genes like glutathione peroxidase 2 (BrGPX2, Bra022853), protein kinases, and phosphatases. Among heat stress (HS) marker genes in Arabidopsis, only exportin 1A (XPO1A) (Bra008580, Bra006382) can be applied to B. rapa for basal thermotolerance (BT) and short-term acquired thermotolerance (SAT) gene. CYP707A3 (Bra025083, Bra021965), which is involved in the dehydration response in Arabidopsis, was associated with membrane leakage in both lines following HS. Although many transcription factors (TF) genes, including DREB2A (Bra005852), were involved in HS tolerance in both lines, Bra024224 (MYB41) and Bra021735 (a bZIP/AIR1 [Anthocyanin-Impaired-Response-1]) were specific to Kenshin. Several candidate TFs involved in thermotolerance were confirmed as HSR genes by real-time PCR, and these assignments were further supported by promoter analysis. Although some of our findings are similar to those obtained using other plant species, clear differences in Brassica rapa reveal a distinct HSR in this species. Our data could also provide a

  19. Linking genes to literature: text mining, information extraction, and retrieval applications for biology.

    PubMed

    Krallinger, Martin; Valencia, Alfonso; Hirschman, Lynette

    2008-01-01

    Efficient access to information contained in online scientific literature collections is essential for life science research, playing a crucial role from the initial stage of experiment planning to the final interpretation and communication of the results. The biological literature also constitutes the main information source for manual literature curation used by expert-curated databases. Following the increasing popularity of web-based applications for analyzing biological data, new text-mining and information extraction strategies are being implemented. These systems exploit existing regularities in natural language to extract biologically relevant information from electronic texts automatically. The aim of the BioCreative challenge is to promote the development of such tools and to provide insight into their performance. This review presents a general introduction to the main characteristics and applications of currently available text-mining systems for life sciences in terms of the following: the type of biological information demands being addressed; the level of information granularity of both user queries and results; and the features and methods commonly exploited by these applications. The current trend in biomedical text mining points toward an increasing diversification in terms of application types and techniques, together with integration of domain-specific resources such as ontologies. Additional descriptions of some of the systems discussed here are available on the internet http://zope.bioinfo.cnio.es/bionlp_tools/. PMID:18834499

  20. Linking genes to literature: text mining, information extraction, and retrieval applications for biology.

    PubMed

    Krallinger, Martin; Valencia, Alfonso; Hirschman, Lynette

    2008-01-01

    Efficient access to information contained in online scientific literature collections is essential for life science research, playing a crucial role from the initial stage of experiment planning to the final interpretation and communication of the results. The biological literature also constitutes the main information source for manual literature curation used by expert-curated databases. Following the increasing popularity of web-based applications for analyzing biological data, new text-mining and information extraction strategies are being implemented. These systems exploit existing regularities in natural language to extract biologically relevant information from electronic texts automatically. The aim of the BioCreative challenge is to promote the development of such tools and to provide insight into their performance. This review presents a general introduction to the main characteristics and applications of currently available text-mining systems for life sciences in terms of the following: the type of biological information demands being addressed; the level of information granularity of both user queries and results; and the features and methods commonly exploited by these applications. The current trend in biomedical text mining points toward an increasing diversification in terms of application types and techniques, together with integration of domain-specific resources such as ontologies. Additional descriptions of some of the systems discussed here are available on the internet http://zope.bioinfo.cnio.es/bionlp_tools/.

  1. Linking genes to literature: text mining, information extraction, and retrieval applications for biology

    PubMed Central

    Krallinger, Martin; Valencia, Alfonso; Hirschman, Lynette

    2008-01-01

    Efficient access to information contained in online scientific literature collections is essential for life science research, playing a crucial role from the initial stage of experiment planning to the final interpretation and communication of the results. The biological literature also constitutes the main information source for manual literature curation used by expert-curated databases. Following the increasing popularity of web-based applications for analyzing biological data, new text-mining and information extraction strategies are being implemented. These systems exploit existing regularities in natural language to extract biologically relevant information from electronic texts automatically. The aim of the BioCreative challenge is to promote the development of such tools and to provide insight into their performance. This review presents a general introduction to the main characteristics and applications of currently available text-mining systems for life sciences in terms of the following: the type of biological information demands being addressed; the level of information granularity of both user queries and results; and the features and methods commonly exploited by these applications. The current trend in biomedical text mining points toward an increasing diversification in terms of application types and techniques, together with integration of domain-specific resources such as ontologies. Additional descriptions of some of the systems discussed here are available on the internet . PMID:18834499

  2. The global regulator genes from biocontrol strain Serratia plymuthica IC1270: cloning, sequencing, and functional studies.

    PubMed

    Ovadis, Marianna; Liu, Xiaoguang; Gavriel, Sagi; Ismailov, Zafar; Chet, Ilan; Chernin, Leonid

    2004-08-01

    The biocontrol activity of various fluorescent pseudomonads towards plant-pathogenic fungi is dependent upon the GacA/GacS-type two-component system of global regulators and the RpoS transcription sigma factor. In particular, these components are required for the production of antifungal antibiotics and exoenzymes. To investigate the effects of these global regulators on the expression of biocontrol factors by plant-associated bacteria other than Pseudomonas spp., gacA/gacS and rpoS homologues were cloned from biocontrol strain IC1270 of Serratia plymuthica, which produces a set of antifungal compounds, including chitinolytic enzymes and the antibiotic pyrrolnitrin. The nucleotide and deduced protein sequence alignments of the cloned gacA/gacS-like genes-tentatively designated grrA (global response regulation activator) and grrS (global response regulation sensor) and of the cloned rpoS gene revealed 64 to 93% identity with matching genes and proteins of the enteric bacteria Escherichia coli, Pectobacterium carotovora subsp. carotovora, and Serratia marcescens. grrA, grrS, and rpoS gene replacement mutants of strain IC1270 were deficient in the production of pyrrolnitrin, an exoprotease, and N-acylhomoserine lactone quorum-sensing signal molecules. However, neither mutant appeared to differ from the parental strain in the production of siderophores, and only grrA and grrS mutants were deficient in the production of a 58-kDa endochitinase, representing the involvement of other sigma factors in the regulation of strain IC1270's chitinolytic activity. Compared to the parental strain, the grrA, grrS, and rpoS mutants were markedly less capable of suppressing Rhizoctonia solani and Pythium aphanidermatum under greenhouse conditions, indicating the dependence of strain IC1270's biocontrol property on the GrrA/GrrS and RpoS global regulators.

  3. SNPranker 2.0: a gene-centric data mining tool for diseases associated SNP prioritization in GWAS

    PubMed Central

    2013-01-01

    Background The capability of correlating specific genotypes with human diseases is a complex issue in spite of all advantages arisen from high-throughput technologies, such as Genome Wide Association Studies (GWAS). New tools for genetic variants interpretation and for Single Nucleotide Polymorphisms (SNPs) prioritization are actually needed. Given a list of the most relevant SNPs statistically associated to a specific pathology as result of a genotype study, a critical issue is the identification of genes that are effectively related to the disease by re-scoring the importance of the identified genetic variations. Vice versa, given a list of genes, it can be of great importance to predict which SNPs can be involved in the onset of a particular disease, in order to focus the research on their effects. Results We propose a new bioinformatics approach to support biological data mining in the analysis and interpretation of SNPs associated to pathologies. This system can be employed to design custom genotyping chips for disease-oriented studies and to re-score GWAS results. The proposed method relies (1) on the data integration of public resources using a gene-centric database design, (2) on the evaluation of a set of static biomolecular annotations, defined as features, and (3) on the SNP scoring function, which computes SNP scores using parameters and weights set by users. We employed a machine learning classifier to set default feature weights and an ontological annotation layer to enable the enrichment of the input gene set. We implemented our method as a web tool called SNPranker 2.0 (http://www.itb.cnr.it/snpranker), improving our first published release of this system. A user-friendly interface allows the input of a list of genes, SNPs or a biological process, and to customize the features set with relative weights. As result, SNPranker 2.0 returns a list of SNPs, localized within input and ontologically enriched genes, combined with their prioritization scores

  4. Global Analysis of WRKY Genes and Their Response to Dehydration and Salt Stress in Soybean

    PubMed Central

    Song, Hui; Wang, Pengfei; Hou, Lei; Zhao, Shuzhen; Zhao, Chuanzhi; Xia, Han; Li, Pengcheng; Zhang, Ye; Bian, Xiaotong; Wang, Xingjun

    2016-01-01

    WRKY proteins are plant specific transcription factors involved in various developmental and physiological processes, especially in biotic and abiotic stress resistance. Although previous studies suggested that WRKY proteins in soybean (Glycine max var. Williams 82) involved in both abiotic and biotic stress responses, the global information of WRKY proteins in the latest version of soybean genome (Wm82.a2v1) and their response to dehydration and salt stress have not been reported. In this study, we identified 176 GmWRKY proteins from soybean Wm82.a2v1 genome. These proteins could be classified into three groups, namely group I (32 proteins), group II (120 proteins), and group III (24 proteins). Our results showed that most GmWRKY genes were located on Chromosome 6, while chromosome 11, 12, and 20 contained the least number of this gene family. More GmWRKY genes were distributed on the ends of chromosomes to compare with other regions. The cis-acting elements analysis suggested that GmWRKY genes were transcriptionally regulated upon dehydration and salt stress. RNA-seq data analysis indicated that three GmWRKY genes responded negatively to dehydration, and 12 genes positively responded to salt stress at 1, 6, and 12 h, respectively. We confirmed by qRT-PCR that the expression of GmWRKY47 and GmWRKY 58 genes was decreased upon dehydration, and the expression of GmWRKY92, 144 and 165 genes was increased under salt treatment. PMID:26870047

  5. Global mining risk footprint of critical metals necessary for low-carbon technologies: the case of neodymium, cobalt, and platinum in Japan.

    PubMed

    Nansai, Keisuke; Nakajima, Kenichi; Kagawa, Shigemi; Kondo, Yasushi; Shigetomi, Yosuke; Suh, Sangwon

    2015-02-17

    Meeting the 2-degree global warming target requires wide adoption of low-carbon energy technologies. Many such technologies rely on the use of precious metals, however, increasing the dependence of national economies on these resources. Among such metals, those with supply security concerns are referred to as critical metals. Using the Policy Potential Index developed by the Fraser Institute, this study developed a new footprint indicator, the mining risk footprint (MRF), to quantify the mining risk directly and indirectly affecting a national economy through its consumption of critical metals. We formulated the MRF as a product of the material footprint (MF) of the consuming country and the mining risks of the countries where the materials are mined. A case study was conducted for the 2005 Japanese economy to determine the MF and MRF for three critical metals essential for emerging energy technologies: neodymium, cobalt and platinum. The results indicate that in 2005 the MFs generated by Japanese domestic final demand, that is, the consumption-based metal output of Japan, were 1.0 × 10(3) t for neodymium, 9.4 × 10(3) t for cobalt, and 2.1 × 10 t for platinum. Export demand contributes most to the MF, accounting for 3.0 × 10(3) t, 1.3 × 10(5) t, and 3.1 × 10 t, respectively. The MRFs of Japanese total final demand (domestic plus export) were calculated to be 1.7 × 10 points for neodymium, 4.5 × 10(-2) points for cobalt, and 5.6 points for platinum, implying that the Japanese economy is incurring a high mining risk through its use of neodymium. This country's MRFs are all dominated by export demand. The paper concludes by discussing the policy implications and future research directions for measuring the MFs and MRFs of critical metals. For countries poorly endowed with mineral resources, adopting low-carbon energy technologies may imply a shifting of risk from carbon resources to other natural resources, in particular critical metals, and a trade

  6. Heavy metals in wild house mice from coal-mining areas of Colombia and expression of genes related to oxidative stress, DNA damage and exposure to metals.

    PubMed

    Guerrero-Castilla, Angélica; Olivero-Verbel, Jesús; Marrugo-Negrete, José

    2014-03-01

    Coal mining is a source of pollutants that impact on environmental and human health. This study examined the metal content and the transcriptional status of gene markers associated with oxidative stress, metal transport and DNA damage in livers of feral mice collected near coal-mining operations, in comparison with mice obtained from a reference site. Mus musculus specimens were caught from La Loma and La Jagua, two coal-mining sites in the north of Colombia, as well as from Valledupar (Cesar Department), a city located 100km north of the mines. Concentrations in liver tissue of Hg, Zn, Pb, Cd, Cu and As were determined by differential stripping voltammetry, and real-time PCR was used to measure gene expression. Compared with the reference group (Valledupar), hepatic concentrations of Cd, Cu and Zn were significantly higher in animals living near mining areas. In exposed animals, the mRNA expression of NQ01, MT1, SOD1, MT2, and DDIT3 was 4.2-, 7.3-, 2.5-, 4.6- and 3.4-fold greater in coal mining sites, respectively, than in animals from the reference site (p<0.05). These results suggest that activities related to coal mining may generate pollutants that could affect the biota, inducing the transcription of biochemical markers related to oxidative stress, metal exposure, and DNA damage. These changes may be in part linked to metal toxicity, and could have implications for the development of chronic disease. Therefore, it is essential to implement preventive measures to minimize the effects of coal mining on its nearby environment, in order to protect human health.

  7. Polymorphisms in metabolism and repair genes affects DNA damage caused by open-cast coal mining exposure.

    PubMed

    Espitia-Pérez, Lyda; Sosa, Milton Quintana; Salcedo-Arteaga, Shirley; León-Mejía, Grethel; Hoyos-Giraldo, Luz Stella; Brango, Hugo; Kvitko, Katia; da Silva, Juliana; Henriques, João A P

    2016-09-15

    Increasing evidence suggest that occupational exposure to open-cast coal mining residues like dust particles, heavy metals and Polycyclic Aromatic Hydrocarbons (PAHs) may cause a wide range of DNA damage and genomic instability that could be associated to initial steps in cancer development and other work-related diseases. The aim of our study was to evaluate if key polymorphisms in metabolism genes CYP1A1Msp1, GSTM1Null, GSTT1Null and DNA repair genes XRCC1Arg194Trp and hOGG1Ser326Cys could modify individual susceptibility to adverse coal exposure effects, considering the DNA damage (Comet assay) and micronucleus formation in lymphocytes (CBMN) and buccal mucosa cells (BMNCyt) as endpoints for genotoxicity. The study population is comprised of 200 healthy male subjects, 100 open-cast coal-mining workers from "El Cerrejón" (world's largest open-cast coal mine located in Guajira - Colombia) and 100 non-exposed referents from general population. The data revealed a significant increase of CBMN frequency in peripheral lymphocytes of occupationally exposed workers carrying the wild-type variant of GSTT1 (+) gene. Exposed subjects carrying GSTT1null polymorphism showed a lower micronucleus frequency compared with their positive counterparts (FR: 0.83; P=0.04), while BMNCyt, frequency and Comet assay parameters in lymphocytes: Damage Index (DI) and percentage of DNA in the tail (Tail % DNA) were significantly higher in exposed workers with the GSTM1Null polymorphism. Other exfoliated buccal mucosa abnormalities related to cell death (Karyorrhexis and Karyolysis) were increased in GSTT/M1Null carriers. Nuclear buds were significantly higher in workers carrying the CYP1A1Msp1 (m1/m2, m2/m2) allele. Moreover, BMNCyt frequency and Comet assay parameters were significantly lower in exposed carriers of XRCC1Arg194Trp (Arg/Trp, Trp/Trp) and hOGG1Ser326Cys (Ser/Cys, Cys/Cys), thereby providing new data to the increasing evidence about the protective role of these polymorphisms

  8. Polymorphisms in metabolism and repair genes affects DNA damage caused by open-cast coal mining exposure.

    PubMed

    Espitia-Pérez, Lyda; Sosa, Milton Quintana; Salcedo-Arteaga, Shirley; León-Mejía, Grethel; Hoyos-Giraldo, Luz Stella; Brango, Hugo; Kvitko, Katia; da Silva, Juliana; Henriques, João A P

    2016-09-15

    Increasing evidence suggest that occupational exposure to open-cast coal mining residues like dust particles, heavy metals and Polycyclic Aromatic Hydrocarbons (PAHs) may cause a wide range of DNA damage and genomic instability that could be associated to initial steps in cancer development and other work-related diseases. The aim of our study was to evaluate if key polymorphisms in metabolism genes CYP1A1Msp1, GSTM1Null, GSTT1Null and DNA repair genes XRCC1Arg194Trp and hOGG1Ser326Cys could modify individual susceptibility to adverse coal exposure effects, considering the DNA damage (Comet assay) and micronucleus formation in lymphocytes (CBMN) and buccal mucosa cells (BMNCyt) as endpoints for genotoxicity. The study population is comprised of 200 healthy male subjects, 100 open-cast coal-mining workers from "El Cerrejón" (world's largest open-cast coal mine located in Guajira - Colombia) and 100 non-exposed referents from general population. The data revealed a significant increase of CBMN frequency in peripheral lymphocytes of occupationally exposed workers carrying the wild-type variant of GSTT1 (+) gene. Exposed subjects carrying GSTT1null polymorphism showed a lower micronucleus frequency compared with their positive counterparts (FR: 0.83; P=0.04), while BMNCyt, frequency and Comet assay parameters in lymphocytes: Damage Index (DI) and percentage of DNA in the tail (Tail % DNA) were significantly higher in exposed workers with the GSTM1Null polymorphism. Other exfoliated buccal mucosa abnormalities related to cell death (Karyorrhexis and Karyolysis) were increased in GSTT/M1Null carriers. Nuclear buds were significantly higher in workers carrying the CYP1A1Msp1 (m1/m2, m2/m2) allele. Moreover, BMNCyt frequency and Comet assay parameters were significantly lower in exposed carriers of XRCC1Arg194Trp (Arg/Trp, Trp/Trp) and hOGG1Ser326Cys (Ser/Cys, Cys/Cys), thereby providing new data to the increasing evidence about the protective role of these polymorphisms

  9. Global assessment of imprinted gene expression in the bovine conceptus by next generation sequencing

    PubMed Central

    Chen, Zhiyuan; Hagen, Darren E.; Wang, Juanbin; Elsik, Christine G.; Ji, Tieming; Siqueira, Luiz G.; Hansen, Peter J.; Rivera, Rocío M.

    2016-01-01

    ABSTRACT Genomic imprinting is an epigenetic mechanism that leads to parental-allele-specific gene expression. Approximately 150 imprinted genes have been identified in humans and mice but less than 30 have been described as imprinted in cattle. For the purpose of de novo identification of imprinted genes in bovine, we determined global monoallelic gene expression in brain, skeletal muscle, liver, kidney and placenta of day ∼105 Bos taurus indicus × Bos taurus taurus F1 conceptuses using RNA sequencing. To accomplish this, we developed a bioinformatics pipeline to identify parent-specific single nucleotide polymorphism alleles after filtering adenosine to inosine (A-to-I) RNA editing sites. We identified 53 genes subject to monoallelic expression. Twenty three are genes known to be imprinted in the cow and an additional 7 have previously been characterized as imprinted in human and/or mouse that have not been reported as imprinted in cattle. Of the remaining 23 genes, we found that 10 are uncharacterized or unannotated transcripts located in known imprinted clusters, whereas the other 13 genes are distributed throughout the bovine genome and are not close to any known imprinted clusters. To exclude potential cis-eQTL effects on allele expression, we corroborated the parental specificity of monoallelic expression in day 86 Bos taurus taurus × Bos taurus taurus conceptuses and identified 8 novel bovine imprinted genes. Further, we identified 671 candidate A-to-I RNA editing sites and describe random X-inactivation in day 15 bovine extraembryonic membranes. Our results expand the imprinted gene list in bovine and demonstrate that monoallelic gene expression can be the result of cis-eQTL effects. PMID:27245094

  10. Differentiation in neutral genes and a candidate gene in the pied flycatcher: using biological archives to track global climate change

    PubMed Central

    Kuhn, Kerstin; Schwenk, Klaus; Both, Christiaan; Canal, David; Johansson, Ulf S; van der Mije, Steven; Töpfer, Till; Päckert, Martin

    2013-01-01

    Global climate change is one of the major driving forces for adaptive shifts in migration and breeding phenology and possibly impacts demographic changes if a species fails to adapt sufficiently. In Western Europe, pied flycatchers (Ficedula hypoleuca) have insufficiently adapted their breeding phenology to the ongoing advance of food peaks within their breeding area and consequently suffered local population declines. We address the question whether this population decline led to a loss of genetic variation, using two neutral marker sets (mitochondrial control region and microsatellites), and one potentially selectively non-neutral marker (avian Clock gene). We report temporal changes in genetic diversity in extant populations and biological archives over more than a century, using samples from sites differing in the extent of climate change. Comparing genetic differentiation over this period revealed that only the recent Dutch population, which underwent population declines, showed slightly lower genetic variation than the historic Dutch population. As that loss of variation was only moderate and not observed in all markers, current gene flow across Western and Central European populations might have compensated local loss of variation over the last decades. A comparison of genetic differentiation in neutral loci versus the Clock gene locus provided evidence for stabilizing selection. Furthermore, in all genetic markers, we found a greater genetic differentiation in space than in time. This pattern suggests that local adaptation or historic processes might have a stronger effect on the population structure and genetic variation in the pied flycatcher than recent global climate changes. PMID:24363905

  11. Global Pattern of Gene Expression of Xanthomonas axonopodis pv. glycines Within Soybean Leaves.

    PubMed

    Chatnaparat, Tiyakhon; Prathuangwong, Sutruedee; Lindow, Steven E

    2016-06-01

    To better understand the behavior of Xanthomonas axonopodis pv. glycines, the causal agent of bacterial pustule of soybean within its host, its global transcriptome within soybean leaves was compared with that in a minimal medium in vitro, using deep sequencing of mRNA. Of 5,062 genes predicted from a draft genome of X. axonopodis pv. glycines, 534 were up-regulated in the plant, while 289 were down-regulated. Genes encoding YapH, a cell-surface adhesin, as well as several others encoding cell-surface proteins, were down-regulated in soybean. Many genes encoding the type III secretion system and effector proteins, cell wall-degrading enzymes and phosphate transporter proteins were strongly expressed at early stages of infection. Several genes encoding RND multidrug efflux pumps were induced in planta and by isoflavonoids in vitro and were required for full virulence of X. axonopodis pv. glycines, as well as resistance to soybean phytoalexins. Genes encoding consumption of malonate, a compound abundant in soybean, were induced in planta and by malonate in vitro. Disruption of the malonate decarboxylase operon blocked growth in minimal media with malonate as the sole carbon source but did not significantly alter growth in soybean, apparently because genes for sucrose and fructose uptake were also induced in planta. Many genes involved in phosphate metabolism and uptake were induced in planta. While disruption of genes encoding high-affinity phosphate transport did not alter growth in media varying in phosphate concentration, the mutants were severely attenuated for growth in soybean. This global transcriptional profiling has provided insight into both the intercellular environment of this soybean pathogen and traits used by X. axonopodis pv. glycines to promote disease. PMID:27003800

  12. Global Pattern of Gene Expression of Xanthomonas axonopodis pv. glycines Within Soybean Leaves.

    PubMed

    Chatnaparat, Tiyakhon; Prathuangwong, Sutruedee; Lindow, Steven E

    2016-06-01

    To better understand the behavior of Xanthomonas axonopodis pv. glycines, the causal agent of bacterial pustule of soybean within its host, its global transcriptome within soybean leaves was compared with that in a minimal medium in vitro, using deep sequencing of mRNA. Of 5,062 genes predicted from a draft genome of X. axonopodis pv. glycines, 534 were up-regulated in the plant, while 289 were down-regulated. Genes encoding YapH, a cell-surface adhesin, as well as several others encoding cell-surface proteins, were down-regulated in soybean. Many genes encoding the type III secretion system and effector proteins, cell wall-degrading enzymes and phosphate transporter proteins were strongly expressed at early stages of infection. Several genes encoding RND multidrug efflux pumps were induced in planta and by isoflavonoids in vitro and were required for full virulence of X. axonopodis pv. glycines, as well as resistance to soybean phytoalexins. Genes encoding consumption of malonate, a compound abundant in soybean, were induced in planta and by malonate in vitro. Disruption of the malonate decarboxylase operon blocked growth in minimal media with malonate as the sole carbon source but did not significantly alter growth in soybean, apparently because genes for sucrose and fructose uptake were also induced in planta. Many genes involved in phosphate metabolism and uptake were induced in planta. While disruption of genes encoding high-affinity phosphate transport did not alter growth in media varying in phosphate concentration, the mutants were severely attenuated for growth in soybean. This global transcriptional profiling has provided insight into both the intercellular environment of this soybean pathogen and traits used by X. axonopodis pv. glycines to promote disease.

  13. Mining microbial metatranscriptomes for expression of antibiotic resistance genes under natural conditions

    PubMed Central

    Versluis, Dennis; D’Andrea, Marco Maria; Ramiro Garcia, Javier; Leimena, Milkha M.; Hugenholtz, Floor; Zhang, Jing; Öztürk, Başak; Nylund, Lotta; Sipkema, Detmer; Schaik, Willem van; de Vos, Willem M.; Kleerebezem, Michiel; Smidt, Hauke; Passel, Mark W.J. van

    2015-01-01

    Antibiotic resistance genes are found in a broad range of ecological niches associated with complex microbiota. Here we investigated if resistance genes are not only present, but also transcribed under natural conditions. Furthermore, we examined the potential for antibiotic production by assessing the expression of associated secondary metabolite biosynthesis gene clusters. Metatranscriptome datasets from intestinal microbiota of four human adults, one human infant, 15 mice and six pigs, of which only the latter have received antibiotics prior to the study, as well as from sea bacterioplankton, a marine sponge, forest soil and sub-seafloor sediment, were investigated. We found that resistance genes are expressed in all studied ecological niches, albeit with niche-specific differences in relative expression levels and diversity of transcripts. For example, in mice and human infant microbiota predominantly tetracycline resistance genes were expressed while in human adult microbiota the spectrum of expressed genes was more diverse, and also included β-lactam, aminoglycoside and macrolide resistance genes. Resistance gene expression could result from the presence of natural antibiotics in the environment, although we could not link it to expression of corresponding secondary metabolites biosynthesis clusters. Alternatively, resistance gene expression could be constitutive, or these genes serve alternative roles besides antibiotic resistance. PMID:26153129

  14. Mining microbial metatranscriptomes for expression of antibiotic resistance genes under natural conditions

    NASA Astrophysics Data System (ADS)

    Versluis, Dennis; D'Andrea, Marco Maria; Ramiro Garcia, Javier; Leimena, Milkha M.; Hugenholtz, Floor; Zhang, Jing; Öztürk, Başak; Nylund, Lotta; Sipkema, Detmer; Schaik, Willem Van; de Vos, Willem M.; Kleerebezem, Michiel; Smidt, Hauke; Passel, Mark W. J. Van

    2015-07-01

    Antibiotic resistance genes are found in a broad range of ecological niches associated with complex microbiota. Here we investigated if resistance genes are not only present, but also transcribed under natural conditions. Furthermore, we examined the potential for antibiotic production by assessing the expression of associated secondary metabolite biosynthesis gene clusters. Metatranscriptome datasets from intestinal microbiota of four human adults, one human infant, 15 mice and six pigs, of which only the latter have received antibiotics prior to the study, as well as from sea bacterioplankton, a marine sponge, forest soil and sub-seafloor sediment, were investigated. We found that resistance genes are expressed in all studied ecological niches, albeit with niche-specific differences in relative expression levels and diversity of transcripts. For example, in mice and human infant microbiota predominantly tetracycline resistance genes were expressed while in human adult microbiota the spectrum of expressed genes was more diverse, and also included β-lactam, aminoglycoside and macrolide resistance genes. Resistance gene expression could result from the presence of natural antibiotics in the environment, although we could not link it to expression of corresponding secondary metabolites biosynthesis clusters. Alternatively, resistance gene expression could be constitutive, or these genes serve alternative roles besides antibiotic resistance.

  15. De Novo Evolution of Complex, Global and Hierarchical Gene Regulatory Mechanisms

    PubMed Central

    Jenkins, Dafyd J.

    2010-01-01

    Gene regulatory networks exhibit complex, hierarchical features such as global regulation and network motifs. There is much debate about whether the evolutionary origins of such features are the results of adaptation, or the by-products of non-adaptive processes of DNA replication. The lack of availability of gene regulatory networks of ancestor species on evolutionary timescales makes this a particularly difficult problem to resolve. Digital organisms, however, can be used to provide a complete evolutionary record of lineages. We use a biologically realistic evolutionary model that includes gene expression, regulation, metabolism and biosynthesis, to investigate the evolution of complex function in gene regulatory networks. We discover that: (i) network architecture and complexity evolve in response to environmental complexity, (ii) global gene regulation is selected for in complex environments, (iii) complex, inter-connected, hierarchical structures evolve in stages, with energy regulation preceding stress responses, and stress responses preceding growth rate adaptations and (iv) robustness of evolved models to mutations depends on hierarchical level: energy regulation and stress responses tend not to be robust to mutations, whereas growth rate adaptations are more robust and non-lethal when mutated. These results highlight the adaptive and incremental evolution of complex biological networks, and the value and potential of studying realistic in silico evolutionary systems as a way of understanding living systems. Electronic supplementary material The online version of this article (doi:10.1007/s00239-010-9369-4) contains supplementary material, which is available to authorized users. PMID:20680619

  16. Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1)

    PubMed Central

    Terranova, Christopher; Narla, Sridhar T.; Lee, Yu-Wei; Bard, Jonathan; Parikh, Abhirath; Stachowiak, Ewa K.; Tzanakakis, Emmanuel S.; Buck, Michael J.; Birkaya, Barbara; Stachowiak, Michal K.

    2015-01-01

    Genetic studies have placed the Fgfr1 gene at the top of major ontogenic pathways that enable gastrulation, tissue development and organogenesis. Using genome-wide sequencing and loss and gain of function experiments the present investigation reveals a mechanism that underlies global and direct gene regulation by the nuclear form of FGFR1, ensuring that pluripotent Embryonic Stem Cells differentiate into Neuronal Cells in response to Retinoic Acid. Nuclear FGFR1, both alone and with its partner nuclear receptors RXR and Nur77, targets thousands of active genes and controls the expression of pluripotency, homeobox, neuronal and mesodermal genes. Nuclear FGFR1 targets genes in developmental pathways represented by Wnt/β-catenin, CREB, BMP, the cell cycle and cancer-related TP53 pathway, neuroectodermal and mesodermal programing networks, axonal growth and synaptic plasticity pathways. Nuclear FGFR1 targets the consensus sequences of transcription factors known to engage CREB-binding protein, a common coregulator of transcription and established binding partner of nuclear FGFR1. This investigation reveals the role of nuclear FGFR1 as a global genomic programmer of cell, neural and muscle development. PMID:25923916

  17. Global gene expression in pseudomyxoma peritonei, with parallel development of two immortalized cell lines.

    PubMed

    Roberts, Darren L; O'Dwyer, Sarah T; Stern, Peter L; Renehan, Andrew G

    2015-05-10

    Pseudomyxoma peritonei (PMP) is a rare tumor of appendiceal origin. Treatment is major cytoreductive surgery but morbidity is high. PMP is considered chemo-resistant; its molecular biology is understudied; and presently, there is no platform for pre-clinical drug testing. Here, we performed exon array analysis from laser micro-dissected PMP tissue and normal colonic epithelia. The array analysis identified 27 up-regulated and 34 down-regulated genes: candidate up-regulated genes included SLC16A4, DSC3, Aldolase B, EPHX4, and ARHGAP24; candidate down-regulated genes were MS4A12, TMIGD1 and Caspase-5. We confirmed differential expression of the candidate genes and their protein products using in-situ hybridization and immuno-histochemistry. In parallel, we established two primary PMP cell lines, N14A and N15A, and immortalized with an SV40 T-antigen lentiviral vector. We cross-checked for expression of the candidate genes (from the array analyses) using qPCR in the cell lines and demonstrated that the gene profiles were distinct from those of colorectal tumor libraries and commonly used colon cell lines. N14A and N15A were responsiveness to mitomycin and oxaliplatin. This study characterizes global gene expression in PMP, and the parallel development of the first immortalized PMP cell lines; fit for pre-clinical testing and PMP oncogene discovery.

  18. Global gene expression in pseudomyxoma peritonei, with parallel development of two immortalized cell lines

    PubMed Central

    Roberts, Darren L.; O'Dwyer, Sarah T.; Stern, Peter L.; Renehan, Andrew G.

    2015-01-01

    Pseudomyxoma peritonei (PMP) is a rare tumor of appendiceal origin. Treatment is major cytoreductive surgery but morbidity is high. PMP is considered chemo-resistant; its molecular biology is understudied; and presently, there is no platform for pre-clinical drug testing. Here, we performed exon array analysis from laser micro-dissected PMP tissue and normal colonic epithelia. The array analysis identified 27 up-regulated and 34 down-regulated genes: candidate up-regulated genes included SLC16A4, DSC3, Aldolase B, EPHX4, and ARHGAP24; candidate down-regulated genes were MS4A12, TMIGD1 and Caspase-5. We confirmed differential expression of the candidate genes and their protein products using in-situ hybridization and immuno-histochemistry. In parallel, we established two primary PMP cell lines, N14A and N15A, and immortalized with an SV40 T-antigen lentiviral vector. We cross-checked for expression of the candidate genes (from the array analyses) using qPCR in the cell lines and demonstrated that the gene profiles were distinct from those of colorectal tumor libraries and commonly used colon cell lines. N14A and N15A were responsiveness to mitomycin and oxaliplatin. This study characterizes global gene expression in PMP, and the parallel development of the first immortalized PMP cell lines; fit for pre-clinical testing and PMP oncogene discovery. PMID:25929336

  19. Potential impact of human mitochondrial replacement on global policy regarding germline gene modification.

    PubMed

    Ishii, Tetsuya

    2014-08-01

    Previous discussions regarding human germline gene modification led to a global consensus that no germline should undergo genetic modification. However, the UK Human Fertilisation and Embryology Authority, having conducted at the UK Government's request a scientific review and a wide public consultation, provided advice to the Government on the pros and cons of Parliament's lifting a ban on altering mitochondrial DNA content of human oocytes and embryos, so as to permit the prevention of maternal transmission of mitochondrial diseases. In this commentary, relevant ethical and biomedical issues are examined and requirements for proceeding with this novel procedure are suggested. Additionally, potentially significant impacts of the UK legalization on global policy concerning germline gene modification are discussed in the context of recent advances in genome-editing technology. It is concluded that international harmonization is needed, as well as further ethical and practical consideration, prior to the legalization of human mitochondrial replacement.

  20. Potential impact of human mitochondrial replacement on global policy regarding germline gene modification.

    PubMed

    Ishii, Tetsuya

    2014-08-01

    Previous discussions regarding human germline gene modification led to a global consensus that no germline should undergo genetic modification. However, the UK Human Fertilisation and Embryology Authority, having conducted at the UK Government's request a scientific review and a wide public consultation, provided advice to the Government on the pros and cons of Parliament's lifting a ban on altering mitochondrial DNA content of human oocytes and embryos, so as to permit the prevention of maternal transmission of mitochondrial diseases. In this commentary, relevant ethical and biomedical issues are examined and requirements for proceeding with this novel procedure are suggested. Additionally, potentially significant impacts of the UK legalization on global policy concerning germline gene modification are discussed in the context of recent advances in genome-editing technology. It is concluded that international harmonization is needed, as well as further ethical and practical consideration, prior to the legalization of human mitochondrial replacement. PMID:24832374

  1. Functional Metagenome Mining of Soil for a Novel Gentamicin Resistance Gene.

    PubMed

    Im, Hyunjoo; Kim, Kyung Mo; Lee, Sang-Heon; Ryu, Choong-Min

    2016-03-01

    Extensive use of antibiotics over recent decades has led to bacterial resistance against antibiotics, including gentamicin, one of the most effective aminoglycosides. The emergence of resistance is problematic for hospitals, since gentamicin is an important broad-spectrum antibiotic for the control of bacterial pathogens in the clinic. Previous study to identify gentamicin resistance genes from environmental samples have been conducted using culture-dependent screening methods. To overcome these limitations, we employed a metagenome-based culture-independent protocol to identify gentamicin resistance genes. Through functional screening of metagenome libraries derived from soil samples, a fosmid clone was selected as it conferred strong gentamicin resistance. To identify a specific functioning gene conferring gentamicin resistance from a selected fosmid clone (35-40 kb), a shot-gun library was constructed and four shot-gun clones (2-3 kb) were selected. Further characterization of these clones revealed that they contained sequences similar to that of the RNA ligase, T4 rnlA that is known as a toxin gene. The overexpression of the rnlA-like gene in Escherichia coli increased gentamicin resistance, indicating that this toxin gene modulates this trait. The results of our metagenome library analysis suggest that the rnlA-like gene may represent a new class of gentamicin resistance genes in pathogenic bacteria. In addition, we demonstrate that the soil metagenome can provide an important resource for the identification of antibiotic resistance genes, which are valuable molecular targets in efforts to overcome antibiotic resistance. PMID:26699755

  2. The global gene expression profile of the secondary transition during pancreatic development.

    PubMed

    Willmann, Stefanie J; Mueller, Nikola S; Engert, Silvia; Sterr, Michael; Burtscher, Ingo; Raducanu, Aurelia; Irmler, Martin; Beckers, Johannes; Sass, Steffen; Theis, Fabian J; Lickert, Heiko

    2016-02-01

    Pancreas organogenesis is a highly dynamic process where neighboring tissue interactions lead to dynamic changes in gene regulatory networks that orchestrate endocrine, exocrine, and ductal lineage formation. To understand the spatio-temporal regulatory logic we have used the Forkhead transcription factor Foxa2-Venus fusion (FVF) knock-in reporter mouse to separate the FVF(+) pancreatic epithelium from the FVF(−) surrounding tissue (mesenchyme, neurons, blood, and blood vessels) to perform a genome-wide mRNA expression profiling at embryonic days (E) 12.5-15.5. Annotating genes and molecular processes suggest that FVF marks endoderm-derived multipotent epithelial progenitors at several lineage restriction steps, when the bulk of endocrine, exocrine and ductal cells are formed during the secondary transition. In the pancreatic epithelial compartment, we identified most known endocrine and exocrine lineage determining factors and diabetes-associated genes, but also unknown genes with spatio-temporal regulated pancreatic expression. In the non-endoderm-derived compartment, we identified many well-described regulatory genes that are not yet functionally annotated in pancreas development, emphasizing that neighboring tissue interactions are still ill defined. Pancreatic expression of over 635 genes was analyzed with them RNA in situ hybridization Genepaint public database. This validated the quality of the profiling data set and identified hundreds of genes with spatially restricted expression patterns in the pancreas. Some of these genes are also targeted by pancreatic transcription factors and show active chromatin marks in human islets of Langerhans. Thus, with the highest spatio-temporal resolution of a global gene expression profile during the secondary transition, our study enables to shed light on neighboring tissue interactions, developmental timing and diabetes gene regulation. PMID:26643664

  3. The global gene expression profile of the secondary transition during pancreatic development.

    PubMed

    Willmann, Stefanie J; Mueller, Nikola S; Engert, Silvia; Sterr, Michael; Burtscher, Ingo; Raducanu, Aurelia; Irmler, Martin; Beckers, Johannes; Sass, Steffen; Theis, Fabian J; Lickert, Heiko

    2016-02-01

    Pancreas organogenesis is a highly dynamic process where neighboring tissue interactions lead to dynamic changes in gene regulatory networks that orchestrate endocrine, exocrine, and ductal lineage formation. To understand the spatio-temporal regulatory logic we have used the Forkhead transcription factor Foxa2-Venus fusion (FVF) knock-in reporter mouse to separate the FVF(+) pancreatic epithelium from the FVF(−) surrounding tissue (mesenchyme, neurons, blood, and blood vessels) to perform a genome-wide mRNA expression profiling at embryonic days (E) 12.5-15.5. Annotating genes and molecular processes suggest that FVF marks endoderm-derived multipotent epithelial progenitors at several lineage restriction steps, when the bulk of endocrine, exocrine and ductal cells are formed during the secondary transition. In the pancreatic epithelial compartment, we identified most known endocrine and exocrine lineage determining factors and diabetes-associated genes, but also unknown genes with spatio-temporal regulated pancreatic expression. In the non-endoderm-derived compartment, we identified many well-described regulatory genes that are not yet functionally annotated in pancreas development, emphasizing that neighboring tissue interactions are still ill defined. Pancreatic expression of over 635 genes was analyzed with them RNA in situ hybridization Genepaint public database. This validated the quality of the profiling data set and identified hundreds of genes with spatially restricted expression patterns in the pancreas. Some of these genes are also targeted by pancreatic transcription factors and show active chromatin marks in human islets of Langerhans. Thus, with the highest spatio-temporal resolution of a global gene expression profile during the secondary transition, our study enables to shed light on neighboring tissue interactions, developmental timing and diabetes gene regulation.

  4. Mining for Nonribosomal Peptide Synthetase and Polyketide Synthase Genes Revealed a High Level of Diversity in the Sphagnum Bog Metagenome

    PubMed Central

    Müller, Christina A.; Oberauner-Wappis, Lisa; Peyman, Armin; Amos, Gregory C. A.; Wellington, Elizabeth M. H.

    2015-01-01

    Sphagnum bog ecosystems are among the oldest vegetation forms harboring a specific microbial community and are known to produce an exceptionally wide variety of bioactive substances. Although the Sphagnum metagenome shows a rich secondary metabolism, the genes have not yet been explored. To analyze nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs), the diversity of NRPS and PKS genes in Sphagnum-associated metagenomes was investigated by in silico data mining and sequence-based screening (PCR amplification of 9,500 fosmid clones). The in silico Illumina-based metagenomic approach resulted in the identification of 279 NRPSs and 346 PKSs, as well as 40 PKS-NRPS hybrid gene sequences. The occurrence of NRPS sequences was strongly dominated by the members of the Protebacteria phylum, especially by species of the Burkholderia genus, while PKS sequences were mainly affiliated with Actinobacteria. Thirteen novel NRPS-related sequences were identified by PCR amplification screening, displaying amino acid identities of 48% to 91% to annotated sequences of members of the phyla Proteobacteria, Actinobacteria, and Cyanobacteria. Some of the identified metagenomic clones showed the closest similarity to peptide synthases from Burkholderia or Lysobacter, which are emerging bacterial sources of as-yet-undescribed bioactive metabolites. This report highlights the role of the extreme natural ecosystems as a promising source for detection of secondary compounds and enzymes, serving as a source for biotechnological applications. PMID:26002894

  5. Mining for Candidate Genes in an Introgression Line by Using RNA Sequencing: The Anthocyanin Overaccumulation Phenotype in Brassica.

    PubMed

    Xie, Lulu; Li, Fei; Zhang, Shifan; Zhang, Hui; Qian, Wei; Li, Peirong; Zhang, Shujiang; Sun, Rifei

    2016-01-01

    Introgression breeding is a widely used method for the genetic improvement of crop plants; however, the mechanism underlying candidate gene flow patterns during hybridization is poorly understood. In this study, we used a powerful pipeline to investigate a Chinese cabbage (Brassica rapa L. ssp. pekinensis) introgression line with the anthocyanin overaccumulation phenotype. Our purpose was to analyze the gene flow patterns during hybridization and elucidate the genetic factors responsible for the accumulation of this important pigment compound. We performed RNA-seq analysis by using two pipelines, one with and one without a reference sequence, to obtain transcriptome data. We identified 930 significantly differentially expressed genes (DEGs) between the purple-leaf introgression line and B. rapa green cultivar, namely, 389 up-regulated and 541 down-regulated DEGs that mapped to the B. rapa reference genome. Since only one anthocyanin pathway regulatory gene was identified, i.e., Bra037887 (bHLH), we mined unmapped reads, revealing 2031 de novo assembled unigenes, including c3563g1i2. Phylogenetic analysis suggested that c3563g1i2, which was transferred from the Brassica B genome of the donor parental line Brassica juncea, may represent an R2R3-MYB transcription factor that participates in the ternary transcriptional activation complex responsible for the anthocyanin overaccumulation phenotype of the B. rapa introgression line. We also identified genes involved in cold and light reaction pathways that were highly upregulated in the introgression line, as confirmed using quantitative real-time PCR analysis. The results of this study shed light on the mechanisms underlying the purple leaf trait in Brassica plants and may facilitate the use of introgressive hybridization for many traits of interest.

  6. Mining for Candidate Genes in an Introgression Line by Using RNA Sequencing: The Anthocyanin Overaccumulation Phenotype in Brassica

    PubMed Central

    Xie, Lulu; Li, Fei; Zhang, Shifan; Zhang, Hui; Qian, Wei; Li, Peirong; Zhang, Shujiang; Sun, Rifei

    2016-01-01

    Introgression breeding is a widely used method for the genetic improvement of crop plants; however, the mechanism underlying candidate gene flow patterns during hybridization is poorly understood. In this study, we used a powerful pipeline to investigate a Chinese cabbage (Brassica rapa L. ssp. pekinensis) introgression line with the anthocyanin overaccumulation phenotype. Our purpose was to analyze the gene flow patterns during hybridization and elucidate the genetic factors responsible for the accumulation of this important pigment compound. We performed RNA-seq analysis by using two pipelines, one with and one without a reference sequence, to obtain transcriptome data. We identified 930 significantly differentially expressed genes (DEGs) between the purple-leaf introgression line and B. rapa green cultivar, namely, 389 up-regulated and 541 down-regulated DEGs that mapped to the B. rapa reference genome. Since only one anthocyanin pathway regulatory gene was identified, i.e., Bra037887 (bHLH), we mined unmapped reads, revealing 2031 de novo assembled unigenes, including c3563g1i2. Phylogenetic analysis suggested that c3563g1i2, which was transferred from the Brassica B genome of the donor parental line Brassica juncea, may represent an R2R3-MYB transcription factor that participates in the ternary transcriptional activation complex responsible for the anthocyanin overaccumulation phenotype of the B. rapa introgression line. We also identified genes involved in cold and light reaction pathways that were highly upregulated in the introgression line, as confirmed using quantitative real-time PCR analysis. The results of this study shed light on the mechanisms underlying the purple leaf trait in Brassica plants and may facilitate the use of introgressive hybridization for many traits of interest.

  7. Mining of Ruminant Microbial Phytase (RPHY1) from Metagenomic Data of Mehsani Buffalo Breed: Identification, Gene Cloning, and Characterization.

    PubMed

    Mootapally, Chandra Shekar; Nathani, Neelam M; Patel, Amrutlal K; Jakhesara, Subhash J; Joshi, Chaitanya G

    2016-01-01

    Phytases have been widely used as animal feed supplements to increase the availability of digestible phosphorus, especially in monogastric animals fed cereal grains. The present study describes the identification of a full-length phytase gene of Prevotella species present in Mehsani buffalo rumen. The gene, designated as RPHY1, consists of 1,251 bp and is expressed into protein with 417 amino acids. A homology search of the deduced amino acid sequence of the RPHY1 phytase gene in a nonredundant protein database showed that it shares 92% similarity with the histidine acid phosphatase domain. Subsequently, the RPHY1 gene was expressed using a pET32a expression vector in Escherichia coli BL21 and purified using a His60 Ni-NTA gravity column. The mass of the purified RPHY1 was estimated to be approximately 63 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The optimal RPHY1 enzyme activity was observed at 55°C (pH 5) and exhibited good stability at 5°C and within the acidic pH range. Significant inhibition of RPHY1 activity was observed for Mg2+ and K+ metal ions, while Ca2+, Mn2+, and Na+ slightly inhibited enzyme activity. The RPHY1 phytase was susceptible to SDS, and it was highly stimulated in the presence of EDTA. Overall, the observed comparatively high enzyme activity levels and characteristics of the RPHY1 gene mined from rumen prove its promising candidature as a feed supplement enzyme in animal farming. PMID:27174428

  8. Mining for Candidate Genes in an Introgression Line by Using RNA Sequencing: The Anthocyanin Overaccumulation Phenotype in Brassica

    PubMed Central

    Xie, Lulu; Li, Fei; Zhang, Shifan; Zhang, Hui; Qian, Wei; Li, Peirong; Zhang, Shujiang; Sun, Rifei

    2016-01-01

    Introgression breeding is a widely used method for the genetic improvement of crop plants; however, the mechanism underlying candidate gene flow patterns during hybridization is poorly understood. In this study, we used a powerful pipeline to investigate a Chinese cabbage (Brassica rapa L. ssp. pekinensis) introgression line with the anthocyanin overaccumulation phenotype. Our purpose was to analyze the gene flow patterns during hybridization and elucidate the genetic factors responsible for the accumulation of this important pigment compound. We performed RNA-seq analysis by using two pipelines, one with and one without a reference sequence, to obtain transcriptome data. We identified 930 significantly differentially expressed genes (DEGs) between the purple-leaf introgression line and B. rapa green cultivar, namely, 389 up-regulated and 541 down-regulated DEGs that mapped to the B. rapa reference genome. Since only one anthocyanin pathway regulatory gene was identified, i.e., Bra037887 (bHLH), we mined unmapped reads, revealing 2031 de novo assembled unigenes, including c3563g1i2. Phylogenetic analysis suggested that c3563g1i2, which was transferred from the Brassica B genome of the donor parental line Brassica juncea, may represent an R2R3-MYB transcription factor that participates in the ternary transcriptional activation complex responsible for the anthocyanin overaccumulation phenotype of the B. rapa introgression line. We also identified genes involved in cold and light reaction pathways that were highly upregulated in the introgression line, as confirmed using quantitative real-time PCR analysis. The results of this study shed light on the mechanisms underlying the purple leaf trait in Brassica plants and may facilitate the use of introgressive hybridization for many traits of interest. PMID:27597857

  9. Mining for Candidate Genes in an Introgression Line by Using RNA Sequencing: The Anthocyanin Overaccumulation Phenotype in Brassica.

    PubMed

    Xie, Lulu; Li, Fei; Zhang, Shifan; Zhang, Hui; Qian, Wei; Li, Peirong; Zhang, Shujiang; Sun, Rifei

    2016-01-01

    Introgression breeding is a widely used method for the genetic improvement of crop plants; however, the mechanism underlying candidate gene flow patterns during hybridization is poorly understood. In this study, we used a powerful pipeline to investigate a Chinese cabbage (Brassica rapa L. ssp. pekinensis) introgression line with the anthocyanin overaccumulation phenotype. Our purpose was to analyze the gene flow patterns during hybridization and elucidate the genetic factors responsible for the accumulation of this important pigment compound. We performed RNA-seq analysis by using two pipelines, one with and one without a reference sequence, to obtain transcriptome data. We identified 930 significantly differentially expressed genes (DEGs) between the purple-leaf introgression line and B. rapa green cultivar, namely, 389 up-regulated and 541 down-regulated DEGs that mapped to the B. rapa reference genome. Since only one anthocyanin pathway regulatory gene was identified, i.e., Bra037887 (bHLH), we mined unmapped reads, revealing 2031 de novo assembled unigenes, including c3563g1i2. Phylogenetic analysis suggested that c3563g1i2, which was transferred from the Brassica B genome of the donor parental line Brassica juncea, may represent an R2R3-MYB transcription factor that participates in the ternary transcriptional activation complex responsible for the anthocyanin overaccumulation phenotype of the B. rapa introgression line. We also identified genes involved in cold and light reaction pathways that were highly upregulated in the introgression line, as confirmed using quantitative real-time PCR analysis. The results of this study shed light on the mechanisms underlying the purple leaf trait in Brassica plants and may facilitate the use of introgressive hybridization for many traits of interest. PMID:27597857

  10. Global Gene Expression Profiling Reveals SPINK1 as a Potential Hepatocellular Carcinoma Marker

    PubMed Central

    Kutter, Claudia; Davies, Susan; Alexander, Graeme; Odom, Duncan T.

    2013-01-01

    Background Liver cirrhosis is the most important risk factor for hepatocellular carcinoma (HCC) but the role of liver disease aetiology in cancer development remains under-explored. We investigated global gene expression profiles from HCC arising in different liver diseases to test whether HCC development is driven by expression of common or different genes, which could provide new diagnostic markers or therapeutic targets. Methodology and Principal Findings Global gene expression profiling was performed for 4 normal (control) livers as well as 8 background liver and 7 HCC from 3 patients with hereditary haemochromatosis (HH) undergoing surgery. In order to investigate different disease phenotypes causing HCC, the data were compared with public microarray repositories for gene expression in normal liver, hepatitis C virus (HCV) cirrhosis, HCV-related HCC (HCV-HCC), hepatitis B virus (HBV) cirrhosis and HBV-related HCC (HBV-HCC). Principal component analysis and differential gene expression analysis were carried out using R Bioconductor. Liver disease-specific and shared gene lists were created and genes identified as highly expressed in hereditary haemochromatosis HCC (HH-HCC) were validated using quantitative RT-PCR. Selected genes were investigated further using immunohistochemistry in 86 HCC arising in liver disorders with varied aetiology. Using a 2-fold cut-off, 9 genes were highly expressed in all HCC, 11 in HH-HCC, 270 in HBV-HCC and 9 in HCV-HCC. Six genes identified by microarray as highly expressed in HH-HCC were confirmed by RT qPCR. Serine peptidase inhibitor, Kazal type 1 (SPINK1) mRNA was very highly expressed in HH-HCC (median fold change 2291, p = 0.0072) and was detected by immunohistochemistry in 91% of HH-HCC, 0% of HH-related cirrhotic or dysplastic nodules and 79% of mixed-aetiology HCC. Conclusion HCC, arising from diverse backgrounds, uniformly over-express a small set of genes. SPINK1, a secretory trypsin inhibitor, demonstrated

  11. Ubiquitous cyanobacterial podoviruses in the global oceans unveiled through viral DNA polymerase gene sequences.

    PubMed

    Huang, Sijun; Wilhelm, Steven W; Jiao, Nianzhi; Chen, Feng

    2010-10-01

    As a major cyanophage group, cyanobacterial podoviruses are important in regulating the biomass and population structure of picocyanobacteria in the ocean. However, little is known about their biogeography in the open ocean. This study represents the first survey of the biodiversity of cyanopodoviruses in the global oceans based on the viral encoded DNA polymerase (pol) gene. A total of 303 DNA pol sequences were amplified by PCR from 10 virus communities collected in the Atlantic and Pacific oceans and the South China Sea. At least five subclusters of cyanopodoviruses were identified in these samples, and one subcluster (subcluster VIII) was found in all sampling sites and comprised approximately 50% of total sequences. The diversity index based on the DNA pol gene sequences recovered through PCR suggests that cyanopodoviruses are less diverse in these oceanic samples than in a previously studied estuarine environment. Although diverse podoviruses were present in the global ocean, each sample was dominated by one major group of cyanopodoviruses. No clear biogeographic patterns were observed using statistical analysis. A metagenomic analysis based on the Global Ocean Sampling database indicates that other types of cyanopodovirus-like DNA pol sequences were present in the global ocean. Together, our study results suggest that cyanopodoviruses are widely distributed in the ocean but their community composition varies with local environments.

  12. Phosphorylation Events in the Multiple Gene Regulator of Group A Streptococcus Significantly Influence Global Gene Expression and Virulence

    PubMed Central

    Sanson, Misu; Makthal, Nishanth; Gavagan, Maire; Cantu, Concepcion; Olsen, Randall J.; Musser, James M.

    2015-01-01

    Whole-genome sequencing analysis of ∼800 strains of group A Streptococcus (GAS) found that the gene encoding the multiple virulence gene regulator of GAS (mga) is highly polymorphic in serotype M59 strains but not in strains of other serotypes. To help understand the molecular mechanism of gene regulation by Mga and its contribution to GAS pathogenesis in serotype M59 GAS, we constructed an isogenic mga mutant strain. Transcriptome studies indicated a significant regulatory influence of Mga and altered metabolic capabilities conferred by Mga-regulated genes. We assessed the phosphorylation status of Mga in GAS cell lysates with Phos-tag gels. The results revealed that Mga is phosphorylated at histidines in vivo. Using phosphomimetic and nonphosphomimetic substitutions at conserved phosphoenolpyruvate:carbohydrate phosphotransferase regulation domain (PRD) histidines of Mga, we demonstrated that phosphorylation-mimicking aspartate replacements at H207 and H273 of PRD-1 and at H327 of PRD-2 are inhibitory to Mga-dependent gene expression. Conversely, non-phosphorylation-mimicking alanine substitutions at H273 and H327 relieved inhibition, and the mutant strains exhibited a wild-type phenotype. The opposing regulatory profiles observed for phosphorylation- and non-phosphorylation-mimicking substitutions at H273 extended to global gene regulation by Mga. Consistent with these observations, the H273D mutant strain attenuated GAS virulence, whereas the H273A strain exhibited a wild-type virulence phenotype in a mouse model of necrotizing fasciitis. Together, our results demonstrate phosphoregulation of Mga and its direct link to virulence in M59 GAS strains. These data also lay a foundation toward understanding how naturally occurring gain-of-function variations in mga, such as H201R, may confer an advantage to the pathogen and contribute to M59 GAS pathogenesis. PMID:25824840

  13. Manteia, a predictive data mining system for vertebrate genes and its applications to human genetic diseases.

    PubMed

    Tassy, Olivier; Pourquié, Olivier

    2014-01-01

    The function of genes is often evolutionarily conserved, and comparing the annotation of ortholog genes in different model organisms has proved to be a powerful predictive tool to identify the function of human genes. Here, we describe Manteia, a resource available online at http://manteia.igbmc.fr. Manteia allows the comparison of embryological, expression, molecular and etiological data from human, mouse, chicken and zebrafish simultaneously to identify new functional and structural correlations and gene-disease associations. Manteia is particularly useful for the analysis of gene lists produced by high-throughput techniques such as microarrays or proteomics. Data can be easily analyzed statistically to characterize the function of groups of genes and to correlate the different aspects of their annotation. Sophisticated querying tools provide unlimited ways to merge the information contained in Manteia along with the possibility of introducing custom user-designed biological questions into the system. This allows for example to connect all the animal experimental results and annotations to the human genome, and take advantage of data not available for human to look for candidate genes responsible for genetic disorders. Here, we demonstrate the predictive and analytical power of the system to predict candidate genes responsible for human genetic diseases.

  14. Global Effects of Inactivation of the Pyruvate Kinase Gene in the Mycobacterium tuberculosis Complex▿ †

    PubMed Central

    Chavadi, Sivagamisundaram; Wooff, Esen; Coldham, Nicholas G.; Sritharan, Manjula; Hewinson, R. Glyn; Gordon, Stephen V.; Wheeler, Paul R.

    2009-01-01

    To better understand the global effects of “natural” lesions in genes involved in the pyruvate metabolism in Mycobacterium bovis, null mutations were made in the Mycobacterium tuberculosis H37Rv ald and pykA genes to mimic the M. bovis situation. Like M. bovis, the M. tuberculosis ΔpykA mutant yielded dysgonic colonies on solid medium lacking pyruvate, whereas colony morphology was eugonic on pyruvate-containing medium. Global effects of the loss of the pykA gene, possibly underlying colony morphology, were investigated by using proteomics on cultures grown in the same conditions. The levels of Icd2 increased and those of Icl and PckA decreased in the ΔpykA knockout. Proteomics suggested that the synthesis of enzymes involved in fatty acid and lipid biosynthesis were decreased, whereas those involved in β-oxidation were increased in the M. tuberculosis ΔpykA mutant, as confirmed by direct assays for these activities. Thus, the loss of pykA from M. tuberculosis results in fatty acids being used principally for energy production, in contrast to the situation in the host when carbon from fatty acids is conserved through the glyoxylate cycle and gluconeogenesis; when an active pykA gene was introduced into M. bovis, the opposite effects occurred. Proteins involved in oxidative stress—AhpC, KatG, and SodA—showed increased synthesis in the ΔpykA mutant, and iron-regulated proteins were also affected. Ald levels were decreased in the ΔpykA knockout, explaining why an M. tuberculosis ΔpykA Δald double mutant showed little additional phenotypic effect. Overall, these data show that the loss of the pykA gene has powerful, global effects on proteins associated with central metabolism. PMID:19820096

  15. Expression of immunoregulatory genes and its relationship to lead exposure and lead-mediated oxidative stress in wild ungulates from an abandoned mining area.

    PubMed

    Rodríguez-Estival, Jaime; de la Lastra, José M Pérez; Ortiz-Santaliestra, Manuel E; Vidal, Dolors; Mateo, Rafael

    2013-04-01

    Lead (Pb) is a highly toxic metal that can induce oxidative stress and affect the immune system by modifying the expression of immunomodulator-related genes. The aim of the present study was to investigate the association between Pb exposure and the transcriptional profiles of some cytokines, as well as the relationship between Pb exposure and changes in oxidative stress biomarkers observed in the spleen of wild ungulates exposed to mining pollution. Red deer and wild boar from the mining area studied had higher spleen, liver, and bone Pb levels than controls, indicating a chronic exposure to Pb pollution. Such exposure caused a depletion of spleen glutathione levels in both species and disrupted the activity of antioxidant enzymes, suggesting the generation of oxidative stress conditions. Deer from the mining area also showed an induced T-helper (Th )-dependent immune response toward the Th 2 pathway, whereas boar from the mining area showed a cytokine profile suggesting an inclination of the immune response toward the Th 1 pathway. These results indicate that environmental exposure to Pb may alter immune responses in wild ungulates exposed to mining pollution. However, evidence of direct relationships between Pb-mediated oxidative stress and the changes detected in immune responses were not found. Further research is needed to evaluate the immunotoxic potential of Pb pollution, also considering the prevalence of chronic infectious diseases in wildlife in environments affected by mining activities.

  16. Effect of starvation on global gene expression and proteolysis in rainbow trout (Oncorhynchus mykiss)

    PubMed Central

    Salem, Mohamed; Silverstein, Jeff; Rexroad, Caird E; Yao, Jianbo

    2007-01-01

    Background Fast, efficiently growing animals have increased protein synthesis and/or reduced protein degradation relative to slow, inefficiently growing animals. Consequently, minimizing the energetic cost of protein turnover is a strategic goal for enhancing animal growth. Characterization of gene expression profiles associated with protein turnover would allow us to identify genes that could potentially be used as molecular biomarkers to select for germplasm with improved protein accretion. Results We evaluated changes in hepatic global gene expression in response to 3-week starvation in rainbow trout (Oncorhynchus mykiss). Microarray analysis revealed a coordinated, down-regulated expression of protein biosynthesis genes in starved fish. In addition, the expression of genes involved in lipid metabolism/transport, aerobic respiration, blood functions and immune response were decreased in response to starvation. However, the microarray approach did not show a significant increase of gene expression in protein catabolic pathways. Further studies, using real-time PCR and enzyme activity assays, were performed to investigate the expression of genes involved in the major proteolytic pathways including calpains, the multi-catalytic proteasome and cathepsins. Starvation reduced mRNA expression of the calpain inhibitor, calpastatin long isoform (CAST-L), with a subsequent increase in the calpain catalytic activity. In addition, starvation caused a slight but significant increase in 20S proteasome activity without affecting mRNA levels of the proteasome genes. Neither the mRNA levels nor the activities of cathepsin D and L were affected by starvation. Conclusion These results suggest a significant role of calpain and 20S proteasome pathways in protein mobilization as a source of energy during fasting and a potential association of the CAST-L gene with fish protein accretion. PMID:17880706

  17. Global gene profiling of aging lungs in Atp8b1 mutant mice

    PubMed Central

    Soundararajan, Ramani; Stearns, Timothy M.; Czachor, Alexander; Fukumoto, Jutaro; Turn, Christina; Westermann-Clark, Emma; Breitzig, Mason; Tan, Lee; Lockey, Richard F.; King, Benjamin L.; Kolliputi, Narasaiah

    2016-01-01

    Objective Recent studies implicate cardiolipin oxidation in several age-related diseases. Atp8b1 encoding Type 4 P-type ATPases is a cardiolipin transporter. Mutation in Atp8b1 gene or inflammation of the lungs impairs the capacity of Atp8b1 to clear cardiolipin from lung fluid. However, the link between Atp8b1 mutation and age-related gene alteration is unknown. Therefore, we investigated how Atp8b1 mutation alters age-related genes. Methods We performed Affymetrix gene profiling of lungs isolated from young (7-9 wks, n=6) and aged (14 months, 14 M, n=6) C57BL/6 and Atp8b1 mutant mice. In addition, Ingenuity Pathway Analysis (IPA) was performed. Differentially expressed genes were validated by quantitative real-time PCR (qRT-PCR). Results Global transcriptome analysis revealed 532 differentially expressed genes in Atp8b1 lungs, 157 differentially expressed genes in C57BL/6 lungs, and 37 overlapping genes. IPA of age-related genes in Atp8b1 lungs showed enrichment of Xenobiotic metabolism and Nrf2-mediated signaling pathways. The increase in Adamts2 and Mmp13 transcripts in aged Atp8b1 lungs was validated by qRT-PCR. Similarly, the decrease in Col1a1 and increase in Cxcr6 transcripts was confirmed in both Atp8b1 mutant and C57BL/6 lungs. Conclusion Based on transcriptome profiling, our study indicates that Atp8b1 mutant mice may be susceptible to age-related lung diseases. PMID:27689529

  18. Global brain delivery of neprilysin gene by intravascular administration of AAV vector in mice

    PubMed Central

    Iwata, Nobuhisa; Sekiguchi, Misaki; Hattori, Yoshino; Takahashi, Akane; Asai, Masashi; Ji, Bin; Higuchi, Makoto; Staufenbiel, Matthias; Muramatsu, Shin-ichi; Saido, Takaomi C.

    2013-01-01

    Accumulation of amyloid-β peptide (Aβ) in the brain is closely associated with cognitive decline in Alzheimer's disease (AD). Stereotaxic infusion of neprilysin-encoding viral vectors into the hippocampus has been shown to decrease Aβ in AD-model mice, but more efficient and global delivery is necessary to treat the broadly distributed burden in AD. Here we developed an adeno-associated virus (AAV) vector capable of providing neuronal gene expression throughout the brains after peripheral administration. A single intracardiac administration of the vector carrying neprilysin gene in AD-model mice elevated neprilysin activity broadly in the brain, and reduced Aβ oligomers, with concurrent alleviation of abnormal learning and memory function and improvement of amyloid burden. The exogenous neprilysin was localized mainly in endosomes, thereby effectively excluding Aβ oligomers from the brain. AAV vector-mediated gene transfer may provide a therapeutic strategy for neurodegenerative diseases, where global transduction of a therapeutic gene into the brain is necessary. PMID:23503602

  19. Data Mining of Gene Arrays for Biomarkers of Survival in Ovarian Cancer

    PubMed Central

    Coveney, Clare; Boocock, David J.; Rees, Robert C.; Deen, Suha; Ball, Graham R.

    2015-01-01

    The expected five-year survival rate from a stage III ovarian cancer diagnosis is a mere 22%; this applies to the 7000 new cases diagnosed yearly in the UK. Stratification of patients with this heterogeneous disease, based on active molecular pathways, would aid a targeted treatment improving the prognosis for many cases. While hundreds of genes have been associated with ovarian cancer, few have yet been verified by peer research for clinical significance. Here, a meta-analysis approach was applied to two carefully selected gene expression microarray datasets. Artificial neural networks, Cox univariate survival analyses and T-tests identified genes whose expression was consistently and significantly associated with patient survival. The rigor of this experimental design increases confidence in the genes found to be of interest. A list of 56 genes were distilled from a potential 37,000 to be significantly related to survival in both datasets with a FDR of 1.39859 × 10−11, the identities of which both verify genes already implicated with this disease and provide novel genes and pathways to pursue. Further investigation and validation of these may lead to clinical insights and have potential to predict a patient’s response to treatment or be used as a novel target for therapy.

  20. Mining metastasis related genes by primary-secondary tumor comparisons from large-scale databases

    PubMed Central

    Kim, Sangwoo; Lee, Doheon

    2009-01-01

    Background Metastasis is the most dangerous step in cancer progression and causes more than 90% of cancer death. Although many researchers have been working on biological features and characteristics of metastasis, most of its genetic level processes remain uncertain. Some studies succeeded in elucidating metastasis related genes and pathways, followed by predicting prognosis of cancer patients, but there still is a question whether the result genes or pathways contain enough information and noise features have been controlled appropriately. Methods We set four tumor type classes composed of various tumor characteristics such as tissue origin, cellular environment, and metastatic ability. We conducted a set of comparisons among the four tumor classes followed by searching for genes that are consistently up or down regulated through the whole comparisons. Results We identified four sets of genes that are consistently differently expressed in the comparisons, each of which denotes one of four cellular characteristics respectively – liver tissue, colon tissue, liver viability and metastasis characteristics. We found that our candidate genes for tissue specificity are consistent with the TiGER database. And we also found that the metastasis candidate genes from our method were more consistent with the known biological background and independent from other noise features. Conclusion We suggested a new method for identifying metastasis related genes from a large-scale database. The proposed method attempts to minimize the influences from other factors except metastatic ability including tissue originality and tissue viability by confining the result of metastasis unrelated test combinations. PMID:19344478

  1. Bacterial growth: global effects on gene expression, growth feedback and proteome partition.

    PubMed

    Klumpp, Stefan; Hwa, Terence

    2014-08-01

    The function of endogenous as well as synthetic genetic circuits is generically coupled to the physiological state of the cell. For exponentially growing bacteria, a key characteristic of the state of the cell is the growth rate and thus gene expression is often growth-rate dependent. Here we review recent results on growth-rate dependent gene expression. We distinguish different types of growth-rate dependencies by the mechanisms of regulation involved and the presence or absence of an effect of the gene product on growth. The latter can lead to growth feedback, feedback mediated by changes of the global state of the cell. Moreover, we discuss how growth rate dependence can be used as a guide to study the molecular implementation of physiological regulation.

  2. Global profiling of Shewanella oneidensis MR-1: expression of hypothetical genes and improved functional annotations.

    PubMed

    Kolker, Eugene; Picone, Alex F; Galperin, Michael Y; Romine, Margaret F; Higdon, Roger; Makarova, Kira S; Kolker, Natali; Anderson, Gordon A; Qiu, Xiaoyun; Auberry, Kenneth J; Babnigg, Gyorgy; Beliaev, Alex S; Edlefsen, Paul; Elias, Dwayne A; Gorby, Yuri A; Holzman, Ted; Klappenbach, Joel A; Konstantinidis, Konstantinos T; Land, Miriam L; Lipton, Mary S; McCue, Lee-Ann; Monroe, Matthew; Pasa-Tolic, Ljiljana; Pinchuk, Grigoriy; Purvine, Samuel; Serres, Margrethe H; Tsapin, Sasha; Zakrajsek, Brian A; Zhu, Wenhong; Zhou, Jizhong; Larimer, Frank W; Lawrence, Charles E; Riley, Monica; Collart, Frank R; Yates, John R; Smith, Richard D; Giometti, Carol S; Nealson, Kenneth H; Fredrickson, James K; Tiedje, James M

    2005-02-01

    The gamma-proteobacterium Shewanella oneidensis strain MR-1 is a metabolically versatile organism that can reduce a wide range of organic compounds, metal ions, and radionuclides. Similar to most other sequenced organisms, approximately 40% of the predicted ORFs in the S. oneidensis genome were annotated as uncharacterized "hypothetical" genes. We implemented an integrative approach by using experimental and computational analyses to provide more detailed insight into gene function. Global expression profiles were determined for cells after UV irradiation and under aerobic and suboxic growth conditions. Transcriptomic and proteomic analyses confidently identified 538 hypothetical genes as expressed in S. oneidensis cells both as mRNAs and proteins (33% of all predicted hypothetical proteins). Publicly available analysis tools and databases and the expression data were applied to improve the annotation of these genes. The annotation results were scored by using a seven-category schema that ranked both confidence and precision of the functional assignment. We were able to identify homologs for nearly all of these hypothetical proteins (97%), but could confidently assign exact biochemical functions for only 16 proteins (category 1; 3%). Altogether, computational and experimental evidence provided functional assignments or insights for 240 more genes (categories 2-5; 45%). These functional annotations advance our understanding of genes involved in vital cellular processes, including energy conversion, ion transport, secondary metabolism, and signal transduction. We propose that this integrative approach offers a valuable means to undertake the enormous challenge of characterizing the rapidly growing number of hypothetical proteins with each newly sequenced genome. PMID:15684069

  3. Global profiling of Shewanella oneidensis MR-1: Expression of hypothetical genes and improved functional annotations

    SciTech Connect

    Picone, Alex F.; Galperin, Michael Y.; Romine, Margaret; Higdon, Roger; Makarova, Kira S.; Kolker, Natali; Anderson, Gordon A; Qiu, Xiaoyun; Babnigg, Gyorgy; Beliaev, Alexander S; Edlefsen, Paul; Elias, Dwayne A.; Gorby, Dr. Yuri A.; Holzman, Ted; Klappenbach, Joel; Konstantinidis, Konstantinos T; Land, Miriam L; Lipton, Mary S.; McCue, Lee Ann; Monroe, Matthew; Pasa-Tolic, Ljiljana; Pinchuk, Grigoriy; Purvine, Samuel; Serres, Margrethe H.; Tsapin, Sasha; Zakrajsek, Brian A.; Zhu, Wenguang; Zhou, Jizhong; Larimer, Frank W; Lawrence, Charles E.; Riley, Monica; Collart, Frank; YatesIII, John R.; Smith, Richard D.; Nealson, Kenneth H.; Fredrickson, James K; Tiedje, James M.

    2005-01-01

    The gamma-proteobacterium Shewanella oneidensis strain MR-1 is a metabolically versatile organism that can reduce a wide range of organic compounds, metal ions, and radionuclides. Similar to most other sequenced organisms, approximate to40% of the predicted ORFs in the S. oneidensis genome were annotated as uncharacterized "hypothetical" genes. We implemented an integrative approach by using experimental and computational analyses to provide more detailed insight into gene function. Global expression profiles were determined for cells after UV irradiation and under aerobic and suboxic growth conditions. Transcriptomic and proteomic analyses confidently identified 538 hypothetical genes as expressed in S. oneidensis cells both as mRNAs and proteins (33% of all predicted hypothetical proteins). Publicly available analysis tools and databases and the expression data were applied to improve the annotation of these genes. The annotation results were scored by using a seven-category schema that ranked both confidence and precision of the functional assignment. We were able to identify homologs for nearly all of these hypothetical proteins (97%), but could confidently assign exact biochemical functions for only 16 proteins (category 1; 3%). Altogether, computational and experimental evidence provided functional assignments or insights for 240 more genes (categories 2-5; 45%). These functional annotations advance our understanding of genes involved in vital cellular processes, including energy conversion, ion transport, secondary metabolism, and signal transduction. We propose that this integrative approach offers a valuable means to undertake the enormous challenge of characterizing the rapidly growing number of hypothetical proteins with each newly sequenced genome.

  4. The impacts of neutralized acid mine drainage contaminated water on the expression of selected endocrine-linked genes in juvenile Mozambique tilapia Oreochromis mossambicus exposed in vivo.

    PubMed

    Truter, Johannes Christoff; va Wyk, Johannes Hendrik; Oberholster, Paul Johan; Botha, Anna-Maria

    2014-02-01

    Acid mine drainage (AMD) is a global environmental concern due to detrimental impacts on river ecosystems. Little is however known regarding the biological impacts of neutralized AMD on aquatic vertebrates despite excessive discharge into watercourses. The aim of this investigation was to evaluate the endocrine modulatory potential of neutralized AMD, using molecular biomarkers in the teleost fish Oreochromis mossambicus in exposure studies. Surface water was collected from six locations downstream of a high density sludge (HDS) AMD treatment plant and a reference site unimpacted by AMD. The concentrations of 28 elements, including 22 metals, were quantified in the exposure water in order to identify potential links to altered gene expression. Relatively high concentrations of manganese (~ 10mg/l), nickel (~ 0.1mg/l) and cobalt (~ 0.03 mg/l) were detected downstream of the HDS plant. The expression of thyroid receptor-α (trα), trβ, androgen receptor-1 (ar1), ar2, glucocorticoid receptor-1 (gr1), gr2, mineralocorticoid receptor (mr) and aromatase (cyp19a1b) was quantified in juvenile fish after 48 h exposure. Slight but significant changes were observed in the expression of gr1 and mr in fish exposed to water collected directly downstream of the HDS plant, consisting of approximately 95 percent neutralized AMD. The most pronounced alterations in gene expression (i.e. trα, trβ, gr1, gr2, ar1 and mr) was associated with water collected further downstream at a location with no other apparent contamination vectors apart from the neutralized AMD. The altered gene expression associated with the "downstream" locality coincided with higher concentrations of certain metals relative to the locality adjacent to the HDS plant which may indicate a causative link. The current study provides evidence of endocrine disruptive activity associated with neutralized AMD contamination in regard to alterations in the expression of key genes linked to the thyroid, interrenal and

  5. Prioritization of candidate genes for cattle reproductive traits, based on protein-protein interactions, gene expression, and text-mining.

    PubMed

    Hulsegge, Ina; Woelders, Henri; Smits, Mari; Schokker, Dirkjan; Jiang, Li; Sørensen, Peter

    2013-05-15

    Reproduction is of significant economic importance in dairy cattle. Improved understanding of mechanisms that control estrous behavior and other reproduction traits could help in developing strategies to improve and/or monitor these traits. The objective of this study was to predict and rank genes and processes in brain areas and pituitary involved in reproductive traits in cattle using information derived from three different data sources: gene expression, protein-protein interactions, and literature. We identified 59, 89, 53, 23, and 71 genes in bovine amygdala, dorsal hypothalamus, hippocampus, pituitary, and ventral hypothalamus, respectively, potentially involved in processes underlying estrus and estrous behavior. Functional annotation of the candidate genes points to a number of tissue-specific processes of which the "neurotransmitter/ion channel/synapse" process in the amygdala, "steroid hormone receptor activity/ion binding" in the pituitary, "extracellular region" in the ventral hypothalamus, and "positive regulation of transcription/metabolic process" in the dorsal hypothalamus are most prominent. The regulation of the functional processes in the various tissues operate at different biological levels, including transcriptional, posttranscriptional, extracellular, and intercellular signaling levels.

  6. Structuring osteosarcoma knowledge: an osteosarcoma-gene association database based on literature mining and manual annotation.

    PubMed

    Poos, Kathrin; Smida, Jan; Nathrath, Michaela; Maugg, Doris; Baumhoer, Daniel; Neumann, Anna; Korsching, Eberhard

    2014-01-01

    Osteosarcoma (OS) is the most common primary bone cancer exhibiting high genomic instability. This genomic instability affects multiple genes and microRNAs to a varying extent depending on patient and tumor subtype. Massive research is ongoing to identify genes including their gene products and microRNAs that correlate with disease progression and might be used as biomarkers for OS. However, the genomic complexity hampers the identification of reliable biomarkers. Up to now, clinico-pathological factors are the key determinants to guide prognosis and therapeutic treatments. Each day, new studies about OS are published and complicate the acquisition of information to support biomarker discovery and therapeutic improvements. Thus, it is necessary to provide a structured and annotated view on the current OS knowledge that is quick and easily accessible to researchers of the field. Therefore, we developed a publicly available database and Web interface that serves as resource for OS-associated genes and microRNAs. Genes and microRNAs were collected using an automated dictionary-based gene recognition procedure followed by manual review and annotation by experts of the field. In total, 911 genes and 81 microRNAs related to 1331 PubMed abstracts were collected (last update: 29 October 2013). Users can evaluate genes and microRNAs according to their potential prognostic and therapeutic impact, the experimental procedures, the sample types, the biological contexts and microRNA target gene interactions. Additionally, a pathway enrichment analysis of the collected genes highlights different aspects of OS progression. OS requires pathways commonly deregulated in cancer but also features OS-specific alterations like deregulated osteoclast differentiation. To our knowledge, this is the first effort of an OS database containing manual reviewed and annotated up-to-date OS knowledge. It might be a useful resource especially for the bone tumor research community, as specific

  7. Structuring osteosarcoma knowledge: an osteosarcoma-gene association database based on literature mining and manual annotation.

    PubMed

    Poos, Kathrin; Smida, Jan; Nathrath, Michaela; Maugg, Doris; Baumhoer, Daniel; Neumann, Anna; Korsching, Eberhard

    2014-01-01

    Osteosarcoma (OS) is the most common primary bone cancer exhibiting high genomic instability. This genomic instability affects multiple genes and microRNAs to a varying extent depending on patient and tumor subtype. Massive research is ongoing to identify genes including their gene products and microRNAs that correlate with disease progression and might be used as biomarkers for OS. However, the genomic complexity hampers the identification of reliable biomarkers. Up to now, clinico-pathological factors are the key determinants to guide prognosis and therapeutic treatments. Each day, new studies about OS are published and complicate the acquisition of information to support biomarker discovery and therapeutic improvements. Thus, it is necessary to provide a structured and annotated view on the current OS knowledge that is quick and easily accessible to researchers of the field. Therefore, we developed a publicly available database and Web interface that serves as resource for OS-associated genes and microRNAs. Genes and microRNAs were collected using an automated dictionary-based gene recognition procedure followed by manual review and annotation by experts of the field. In total, 911 genes and 81 microRNAs related to 1331 PubMed abstracts were collected (last update: 29 October 2013). Users can evaluate genes and microRNAs according to their potential prognostic and therapeutic impact, the experimental procedures, the sample types, the biological contexts and microRNA target gene interactions. Additionally, a pathway enrichment analysis of the collected genes highlights different aspects of OS progression. OS requires pathways commonly deregulated in cancer but also features OS-specific alterations like deregulated osteoclast differentiation. To our knowledge, this is the first effort of an OS database containing manual reviewed and annotated up-to-date OS knowledge. It might be a useful resource especially for the bone tumor research community, as specific

  8. Allele Mining in Barley Genetic Resources Reveals Genes of Race-Non-Specific Powdery Mildew Resistance

    PubMed Central

    Spies, Annika; Korzun, Viktor; Bayles, Rosemary; Rajaraman, Jeyaraman; Himmelbach, Axel; Hedley, Pete E.; Schweizer, Patrick

    2012-01-01

    Race-non-specific, or quantitative, pathogen resistance is of high importance to plant breeders due to its expected durability. However, it is usually controlled by multiple quantitative trait loci (QTL) and therefore difficult to handle in practice. Knowing the genes that underlie race-non-specific resistance (NR) would allow its exploitation in a more targeted manner. Here, we performed an association-genetic study in a customized worldwide collection of spring barley accessions for candidate genes of race-NR to the powdery mildew fungus Blumeria graminis f. sp. hordei (Bgh) and combined data with results from QTL mapping as well as functional-genomics approaches. This led to the identification of 11 associated genes with converging evidence for an important role in race-NR in the presence of the Mlo gene for basal susceptibility. Outstanding in this respect was the gene encoding the transcription factor WRKY2. The results suggest that unlocking plant genetic resources and integrating functional-genomic with genetic approaches can accelerate the discovery of genes underlying race-NR in barley and other crop plants. PMID:22629270

  9. The population genomics of begomoviruses: global scale population structure and gene flow

    PubMed Central

    2010-01-01

    Background The rapidly growing availability of diverse full genome sequences from across the world is increasing the feasibility of studying the large-scale population processes that underly observable pattern of virus diversity. In particular, characterizing the genetic structure of virus populations could potentially reveal much about how factors such as geographical distributions, host ranges and gene flow between populations combine to produce the discontinuous patterns of genetic diversity that we perceive as distinct virus species. Among the richest and most diverse full genome datasets that are available is that for the dicotyledonous plant infecting genus, Begomovirus, in the Family Geminiviridae. The begomoviruses all share the same whitefly vector, are highly recombinogenic and are distributed throughout tropical and subtropical regions where they seriously threaten the food security of the world's poorest people. Results We focus here on using a model-based population genetic approach to identify the genetically distinct sub-populations within the global begomovirus meta-population. We demonstrate the existence of at least seven major sub-populations that can further be sub-divided into as many as thirty four significantly differentiated and genetically cohesive minor sub-populations. Using the population structure framework revealed in the present study, we further explored the extent of gene flow and recombination between genetic populations. Conclusions Although geographical barriers are apparently the most significant underlying cause of the seven major population sub-divisions, within the framework of these sub-divisions, we explore patterns of gene flow to reveal that both host range differences and genetic barriers to recombination have probably been major contributors to the minor population sub-divisions that we have identified. We believe that the global Begomovirus population structure revealed here could facilitate population genetics studies

  10. Global Analysis of Transcriptome Responses and Gene Expression Profiles to Cold Stress of Jatropha curcas L.

    PubMed Central

    Wang, Haibo; Zou, Zhurong; Wang, Shasha; Gong, Ming

    2013-01-01

    Background Jatropha curcas L., also called the Physic nut, is an oil-rich shrub with multiple uses, including biodiesel production, and is currently exploited as a renewable energy resource in many countries. Nevertheless, because of its origin from the tropical MidAmerican zone, J. curcas confers an inherent but undesirable characteristic (low cold resistance) that may seriously restrict its large-scale popularization. This adaptive flaw can be genetically improved by elucidating the mechanisms underlying plant tolerance to cold temperatures. The newly developed Illumina Hiseq™ 2000 RNA-seq and Digital Gene Expression (DGE) are deep high-throughput approaches for gene expression analysis at the transcriptome level, using which we carefully investigated the gene expression profiles in response to cold stress to gain insight into the molecular mechanisms of cold response in J. curcas. Results In total, 45,251 unigenes were obtained by assembly of clean data generated by RNA-seq analysis of the J. curcas transcriptome. A total of 33,363 and 912 complete or partial coding sequences (CDSs) were determined by protein database alignments and ESTScan prediction, respectively. Among these unigenes, more than 41.52% were involved in approximately 128 known metabolic or signaling pathways, and 4,185 were possibly associated with cold resistance. DGE analysis was used to assess the changes in gene expression when exposed to cold condition (12°C) for 12, 24, and 48 h. The results showed that 3,178 genes were significantly upregulated and 1,244 were downregulated under cold stress. These genes were then functionally annotated based on the transcriptome data from RNA-seq analysis. Conclusions This study provides a global view of transcriptome response and gene expression profiling of J. curcas in response to cold stress. The results can help improve our current understanding of the mechanisms underlying plant cold resistance and favor the screening of crucial genes for

  11. Extremely acidophilic protists from acid mine drainage host Rickettsiales-lineage endosymbionts that have intervening sequences in their 16S rRNA genes.

    PubMed

    Baker, Brett J; Hugenholtz, Philip; Dawson, Scott C; Banfield, Jillian F

    2003-09-01

    During a molecular phylogenetic survey of extremely acidic (pH < 1), metal-rich acid mine drainage habitats in the Richmond Mine at Iron Mountain, Calif., we detected 16S rRNA gene sequences of a novel bacterial group belonging to the order Rickettsiales in the Alphaproteobacteria. The closest known relatives of this group (92% 16S rRNA gene sequence identity) are endosymbionts of the protist Acanthamoeba. Oligonucleotide 16S rRNA probes were designed and used to observe members of this group within acidophilic protists. To improve visualization of eukaryotic populations in the acid mine drainage samples, broad-specificity probes for eukaryotes were redesigned and combined to highlight this component of the acid mine drainage community. Approximately 4% of protists in the acid mine drainage samples contained endosymbionts. Measurements of internal pH of the protists showed that their cytosol is close to neutral, indicating that the endosymbionts may be neutrophilic. The endosymbionts had a conserved 273-nucleotide intervening sequence (IVS) in variable region V1 of their 16S rRNA genes. The IVS does not match any sequence in current databases, but the predicted secondary structure forms well-defined stem loops. IVSs are uncommon in rRNA genes and appear to be confined to bacteria living in close association with eukaryotes. Based on the phylogenetic novelty of the endosymbiont sequences and initial culture-independent characterization, we propose the name "Candidatus Captivus acidiprotistae." To our knowledge, this is the first report of an endosymbiotic relationship in an extremely acidic habitat.

  12. Mining of luxS genes from rumen microbial consortia by metagenomic and metatranscriptomic approaches.

    PubMed

    Ghali, Ines; Shinkai, Takumi; Mitsumori, Makoto

    2016-05-01

    Although rumen bacterial communities vary depending on many factors such as diet, age and physiological conditions, a core microbiota exists within the rumen. In many natural environments, some bacteria use a quorum-sensing (QS) system to regulate their physiological activities. However, very limited information is available about QS systems in rumen. To investigate the autoinducer 2 (AI-2)-mediated QS system in rumen, we detected genes (luxS) encoding the AI-2 synthase (LuxS), from three datasets embedded in metagenomics RAST server (MG-RAST) and from a metatranscriptome dataset. We collected 135 luxS genes from the metagenomic datasets, which were presumed to originate from Bacteroidetes, Firmicutes, Fusobacteria and Actinobacteria, and 34 luxS genes from the metatranscriptome dataset, which probably originated from Bacteroidetes, Firmicutes and Spirochaetes. Because the essential amino acids for LuxS activity were conserved in the LuxS homologues predicted from luxS gene sequences from both datasets, the LuxS homologues probably function in the rumen. Since the largest number of sequences of luxS genes were collected from the genera Prevotella, Ruminococcus and Eubacterium, which include many fibrolytic bacteria and constituent members of biofilm on feed particles, an AI-2-mediated QS system is likely involved in biofilm formation and fibrolytic activity in the rumen. PMID:26277986

  13. Global analysis of gene expression by differential display: a mathematical model.

    PubMed

    Yang, Shitao; Liang, Peng

    2006-01-01

    Differential display (DD) is one of the most commonly used approaches for identifying differentially expressed genes. However, there has been lack of an accurate guidance on how many DD polymerase chain reaction (PCR) primer combinations are needed to display most of the genes expressed in a eukaryotic cell. This study critically evaluated the gene coverage by DD as a function of the number of arbitrary primers, the number of 3' bases of an arbitrary primer required to completely match an mRNA target sequence, the additional 5' base match(s) of arbitrary primers in first-strand cDNA recognition, and the length of mRNA tails being analyzed. The resulting new DD mathematical model predicts that 80-160 arbitrary 13mers, when used in combinations with three one-base anchored oligo-dT primers, would allow any given mRNA within a eukaryotic cell to be detected with a 74-93% probability, respectively. The prediction was supported by both computer simulation of the DD process and experimental data from a comprehensive fluorescent DD screening for target genes of tumor-suppressor p53. Thus, this work provides a theoretical foundation upon which global analysis of gene expression by DD can be pursued.

  14. Gene expression profiling--Opening the black box of plant ecosystem responses to global change

    SciTech Connect

    Leakey, A.D.B.; Ainsworth, E.A.; Bernard, S.M.; Markelz, R.J.C.; Ort, D.R.; Placella, S.A.P.; Rogers, A.; Smith, M.D.; Sudderth, E.A.; Weston, D.J.; Wullschleger, S.D.; Yuan, S.

    2009-11-01

    The use of genomic techniques to address ecological questions is emerging as the field of genomic ecology. Experimentation under environmentally realistic conditions to investigate the molecular response of plants to meaningful changes in growth conditions and ecological interactions is the defining feature of genomic ecology. Since the impact of global change factors on plant performance are mediated by direct effects at the molecular, biochemical and physiological scales, gene expression analysis promises important advances in understanding factors that have previously been consigned to the 'black box' of unknown mechanism. Various tools and approaches are available for assessing gene expression in model and non-model species as part of global change biology studies. Each approach has its own unique advantages and constraints. A first generation of genomic ecology studies in managed ecosystems and mesocosms have provided a testbed for the approach and have begun to reveal how the experimental design and data analysis of gene expression studies can be tailored for use in an ecological context.

  15. Global Gene Expression Profiling of Individual Human Oocytes and Embryos Demonstrates Heterogeneity in Early Development

    PubMed Central

    Zeef, Leo; Kimber, Susan J.; Brison, Daniel R.

    2013-01-01

    Early development in humans is characterised by low and variable embryonic viability, reflected in low fecundity and high rates of miscarriage, relative to other mammals. Data from assisted reproduction programmes provides additional evidence that this is largely mediated at the level of embryonic competence and is highly heterogeneous among embryos. Understanding the basis of this heterogeneity has important implications in a number of areas including: the regulation of early human development, disorders of pregnancy, assisted reproduction programmes, the long term health of children which may be programmed in early development, and the molecular basis of pluripotency in human stem cell populations. We have therefore investigated global gene expression profiles using polyAPCR amplification and microarray technology applied to individual human oocytes and 4-cell and blastocyst stage embryos. In order to explore the basis of any variability in detail, each developmental stage is replicated in triplicate. Our data show that although transcript profiles are highly stage-specific, within each stage they are relatively variable. We describe expression of a number of gene families and pathways including apoptosis, cell cycle and amino acid metabolism, which are variably expressed and may be reflective of embryonic developmental competence. Overall, our data suggest that heterogeneity in human embryo developmental competence is reflected in global transcript profiles, and that the vast majority of existing human embryo gene expression data based on pooled oocytes and embryos need to be reinterpreted. PMID:23717564

  16. Gene Expression Profiling - Opening the Black Box of Plant Ecosystem Responses to Global Change

    SciTech Connect

    Ainsworth, Elizabeth A.; Bernard, Stephanie M.; Markelz, R.J. Cody; Ort, Donald R.; Placella, Sarah A.; Rogers, Alistair; Smith, Melinda D; Sudderth, Erika A.; Weston, David; Wullschleger, Stan D; Yuan, Shenghua

    2009-01-01

    The use of genomic techniques to address ecological questions is emerging as the field of genomic ecology. Experimentation under environmentally realistic conditions to investigate the molecular response of plants to meaningful changes in growth conditions and ecological interactions is the defining feature of genomic ecology. Since the impact of global change factors on plant performance are mediated by direct effects at the molecular, biochemical and physiological scales, gene expression analysis promises important advances in understanding factors that have previously been consigned to the black box of unknown mechanism. Various tools and approaches are available for assessing gene expression in model and non-model species as part of global change biology studies. Each approach has its own unique advantages and constraints. A first generation of genomic ecology studies in managed ecosystems and mesocosms have provided a testbed for the approach and have begun to reveal how the experimental design and data analysis of gene expression studies can be tailored for use in an ecological context.

  17. Global Transcriptome Analysis Reveals That Poly(ADP-Ribose) Polymerase 1 Regulates Gene Expression through EZH2

    PubMed Central

    Martin, Kayla A.; Cesaroni, Matteo; Denny, Michael F.; Lupey, Lena N.

    2015-01-01

    Posttranslational modifications, such as poly(ADP-ribosyl)ation (PARylation), regulate chromatin-modifying enzymes, ultimately affecting gene expression. This study explores the role of poly(ADP-ribose) polymerase (PARP) on global gene expression in a lymphoblastoid B cell line. We found that inhibition of PARP catalytic activity with olaparib resulted in global gene deregulation, affecting approximately 11% of the genes expressed. Gene ontology analysis revealed that PARP could exert these effects through transcription factors and chromatin-remodeling enzymes, including the polycomb repressive complex 2 (PRC2) member EZH2. EZH2 mediates the trimethylation of histone H3 at lysine 27 (H3K27me3), a modification associated with chromatin compaction and gene silencing. Both pharmacological inhibition of PARP and knockdown of PARP1 induced the expression of EZH2, which resulted in increased global H3K27me3. Chromatin immunoprecipitation confirmed that PARP1 inhibition led to H3K27me3 deposition at EZH2 target genes, which resulted in gene silencing. Moreover, increased EZH2 expression is attributed to the loss of the occupancy of the transcription repressor E2F4 at the EZH2 promoter following PARP inhibition. Together, these data show that PARP plays an important role in global gene regulation and identifies for the first time a direct role of PARP1 in regulating the expression and function of EZH2. PMID:26370511

  18. Genomic location of the major ribosomal protein gene locus determines Vibrio cholerae global growth and infectivity.

    PubMed

    Soler-Bistué, Alfonso; Mondotte, Juan A; Bland, Michael Jason; Val, Marie-Eve; Saleh, María-Carla; Mazel, Didier

    2015-04-01

    The effects on cell physiology of gene order within the bacterial chromosome are poorly understood. In silico approaches have shown that genes involved in transcription and translation processes, in particular ribosomal protein (RP) genes, localize near the replication origin (oriC) in fast-growing bacteria suggesting that such a positional bias is an evolutionarily conserved growth-optimization strategy. Such genomic localization could either provide a higher dosage of these genes during fast growth or facilitate the assembly of ribosomes and transcription foci by keeping physically close the many components of these macromolecular machines. To explore this, we used novel recombineering tools to create a set of Vibrio cholerae strains in which S10-spec-α (S10), a locus bearing half of the ribosomal protein genes, was systematically relocated to alternative genomic positions. We show that the relative distance of S10 to the origin of replication tightly correlated with a reduction of S10 dosage, mRNA abundance and growth rate within these otherwise isogenic strains. Furthermore, this was accompanied by a significant reduction in the host-invasion capacity in Drosophila melanogaster. Both phenotypes were rescued in strains bearing two S10 copies highly distal to oriC, demonstrating that replication-dependent gene dosage reduction is the main mechanism behind these alterations. Hence, S10 positioning connects genome structure to cell physiology in Vibrio cholerae. Our results show experimentally for the first time that genomic positioning of genes involved in the flux of genetic information conditions global growth control and hence bacterial physiology and potentially its evolution.

  19. Local mobile gene pools rapidly cross species boundaries to create endemicity within global Vibrio cholerae populations.

    PubMed

    Boucher, Yan; Cordero, Otto X; Takemura, Alison; Hunt, Dana E; Schliep, Klaus; Bapteste, Eric; Lopez, Philippe; Tarr, Cheryl L; Polz, Martin F

    2011-01-01

    Vibrio cholerae represents both an environmental pathogen and a widely distributed microbial species comprised of closely related strains occurring in the tropical to temperate coastal ocean across the globe (Colwell RR, Science 274:2025-2031, 1996; Griffith DC, Kelly-Hope LA, Miller MA, Am. J. Trop. Med. Hyg. 75:973-977, 2006; Reidl J, Klose KE, FEMS Microbiol. Rev. 26:125-139, 2002). However, although this implies dispersal and growth across diverse environmental conditions, how locally successful populations assemble from a possibly global gene pool, relatively unhindered by geographic boundaries, remains poorly understood. Here, we show that environmental Vibrio cholerae possesses two, largely distinct gene pools: one is vertically inherited and globally well mixed, and the other is local and rapidly transferred across species boundaries to generate an endemic population structure. While phylogeographic analysis of isolates collected from Bangladesh and the U.S. east coast suggested strong panmixis for protein-coding genes, there was geographic structure in integrons, which are the only genomic islands present in all strains of V. cholerae (Chun J, et al., Proc. Natl. Acad. Sci. U. S. A. 106:15442-15447, 2009) and are capable of acquiring and expressing mobile gene cassettes. Geographic differentiation in integrons arises from high gene turnover, with acquisition from a locally co-occurring sister species being up to twice as likely as exchange with conspecific but geographically distant V. cholerae populations. IMPORTANCE Functional predictions of integron genes show the predominance of secondary metabolism and cell surface modification, which is consistent with a role in competition and predation defense. We suggest that the integron gene pool's distinctness and tempo of sharing are adaptive in allowing rapid conversion of genomes to reflect local ecological constraints. Because the integron is frequently the main element differentiating clinical strains

  20. Heme Signaling Impacts Global Gene Expression, Immunity and Dengue Virus Infectivity in Aedes aegypti

    PubMed Central

    Bottino-Rojas, Vanessa; Talyuli, Octávio A. C.; Jupatanakul, Natapong; Sim, Shuzhen; Dimopoulos, George; Venancio, Thiago M.; Bahia, Ana C.; Sorgine, Marcos H.; Oliveira, Pedro L.; Paiva-Silva, Gabriela O.

    2015-01-01

    Blood-feeding mosquitoes are exposed to high levels of heme, the product of hemoglobin degradation. Heme is a pro-oxidant that influences a variety of cellular processes. We performed a global analysis of heme-regulated Aedes aegypti (yellow fever mosquito) transcriptional changes to better understand influence on mosquito physiology at the molecular level. We observed an iron- and reactive oxygen species (ROS)-independent signaling induced by heme that comprised genes related to redox metabolism. By modulating the abundance of these transcripts, heme possibly acts as a danger signaling molecule. Furthermore, heme triggered critical changes in the expression of energy metabolism and immune response genes, altering the susceptibility towards bacteria and dengue virus. These findings seem to have implications on the adaptation of mosquitoes to hematophagy and consequently on their ability to transmit diseases. Altogether, these results may also contribute to the understanding of heme cell biology in eukaryotic cells. PMID:26275150

  1. Heme Signaling Impacts Global Gene Expression, Immunity and Dengue Virus Infectivity in Aedes aegypti.

    PubMed

    Bottino-Rojas, Vanessa; Talyuli, Octávio A C; Jupatanakul, Natapong; Sim, Shuzhen; Dimopoulos, George; Venancio, Thiago M; Bahia, Ana C; Sorgine, Marcos H; Oliveira, Pedro L; Paiva-Silva, Gabriela O

    2015-01-01

    Blood-feeding mosquitoes are exposed to high levels of heme, the product of hemoglobin degradation. Heme is a pro-oxidant that influences a variety of cellular processes. We performed a global analysis of heme-regulated Aedes aegypti (yellow fever mosquito) transcriptional changes to better understand influence on mosquito physiology at the molecular level. We observed an iron- and reactive oxygen species (ROS)-independent signaling induced by heme that comprised genes related to redox metabolism. By modulating the abundance of these transcripts, heme possibly acts as a danger signaling molecule. Furthermore, heme triggered critical changes in the expression of energy metabolism and immune response genes, altering the susceptibility towards bacteria and dengue virus. These findings seem to have implications on the adaptation of mosquitoes to hematophagy and consequently on their ability to transmit diseases. Altogether, these results may also contribute to the understanding of heme cell biology in eukaryotic cells.

  2. Identification of novel breast cancer-associated transcripts by UniGene database mining and gene expression analysis in normal and malignant cells.

    PubMed

    Laversin, Stéphanie A-S; Phatak, Vinaya M; Powe, Des G; Li, Geng; Miles, Amanda K; Hughes, David C; Ball, Graham R; Ellis, Ian O; Gritzapis, Angelos D; Missitzis, Ioannis; McArdle, Stéphanie E B; Rees, Robert C

    2013-03-01

    Breast cancer is a heterogeneous and complex disease. Although the use of tumor biomarkers has improved individualized breast cancer care, i.e., assessment of risk, diagnosis, prognosis, and prediction of treatment outcome, new markers are required to further improve patient clinical management. In the present study, a search for novel breast cancer-associated genes was performed by mining the UniGene database for expressed sequence tags (ESTs) originating from human normal breast, breast cancer tissue, or breast cancer cell lines. Two hundred and twenty-eight distinct breast-associated UniGene Clusters (BUC1-228) matched the search criteria. Four BUC ESTs (BUC6, BUC9, BUC10, and BUC11) were subsequently selected for extensive in silico database searches, and in vitro analyses through sequencing and RT-PCR based assays on well-characterized cell lines and tissues of normal and cancerous origin. BUC6, BUC9, BUC10, and BUC11 are clustered on 10p11.21-12.1 and showed no homology to any known RNAs. Overall, expression of the four BUC transcripts was high in normal breast and testis tissue, and in some breast cancers; in contrast, BUC was low in other normal tissues, peripheral blood mononuclear cells (PBMCs), and other cancer cell lines. Results to-date suggest that BUC11 and BUC9 translate to protein and BUC11 cytoplasmic and nuclear protein expression was detected in a large cohort of breast cancer samples using immunohistochemistry. This study demonstrates the discovery and expression analysis of a tissue-restricted novel transcript set which is strongly expressed in breast tissue and their application as clinical cancer biomarkers clearly warrants further investigation.

  3. Commercial Data Mining Software

    NASA Astrophysics Data System (ADS)

    Zhang, Qingyu; Segall, Richard S.

    This chapter discusses selected commercial software for data mining, supercomputing data mining, text mining, and web mining. The selected software are compared with their features and also applied to available data sets. The software for data mining are SAS Enterprise Miner, Megaputer PolyAnalyst 5.0, PASW (formerly SPSS Clementine), IBM Intelligent Miner, and BioDiscovery GeneSight. The software for supercomputing are Avizo by Visualization Science Group and JMP Genomics from SAS Institute. The software for text mining are SAS Text Miner and Megaputer PolyAnalyst 5.0. The software for web mining are Megaputer PolyAnalyst and SPSS Clementine . Background on related literature and software are presented. Screen shots of each of the selected software are presented, as are conclusions and future directions.

  4. Mining of hemicellulose and lignin degrading genes from differentially enriched methane producing microbial community.

    PubMed

    Pandit, Prabhakar D; Gulhane, Madhuri K; Khardenavis, Anshuman A; Purohit, Hemant J

    2016-09-01

    Study creates a scenario for enrichment and selection of ligno-hemicellulose degrading genotypes with anaerobic bioreactor as a model using rice straw, vegetable waste and food waste as substrates. Relative discrimination analysis showed that the hydrolytic pathways and associated microbial communities for ligno-hemicellulose degradation were dominatingly colonized with rice straw as substrate. The dominating bacteria were Caldicellulosiruptor, Fervidobacterium, Cytophaga, Ruminococcus, Thermotoga associated with hemicellulose degradation and Burkholderia, Pandorea, Sphingomonas, Spirochaeta, Pseudomonas for lignocellulose hydrolysis. This was further supported by the abundance of anaerobic aromatic compound degrading genes along with genes for xylanase and xylosidase in rice straw enriched community. The metagenome analysis data was validated by evaluation of the biochemical methane potential for these substrates. Food waste being most amenable substrate yielded 1410mL of biogas/gVS added whereas, biogas yield of 1160mL/gVS and 1080mL/gVS was observed in presence of vegetable waste and rice straw respectively.

  5. Mining predicted essential genes of Brugia malayi for nematode drug targets.

    PubMed

    Kumar, Sanjay; Chaudhary, Kshitiz; Foster, Jeremy M; Novelli, Jacopo F; Zhang, Yinhua; Wang, Shiliang; Spiro, David; Ghedin, Elodie; Carlow, Clotilde K S

    2007-01-01

    We report results from the first genome-wide application of a rational drug target selection methodology to a metazoan pathogen genome, the completed draft sequence of Brugia malayi, a parasitic nematode responsible for human lymphatic filariasis. More than 1.5 billion people worldwide are at risk of contracting lymphatic filariasis and onchocerciasis, a related filarial disease. Drug treatments for filariasis have not changed significantly in over 20 years, and with the risk of resistance rising, there is an urgent need for the development of new anti-filarial drug therapies. The recent publication of the draft genomic sequence for B. malayi enables a genome-wide search for new drug targets. However, there is no functional genomics data in B. malayi to guide the selection of potential drug targets. To circumvent this problem, we have utilized the free-living model nematode Caenorhabditis elegans as a surrogate for B. malayi. Sequence comparisons between the two genomes allow us to map C. elegans orthologs to B. malayi genes. Using these orthology mappings and by incorporating the extensive genomic and functional genomic data, including genome-wide RNAi screens, that already exist for C. elegans, we identify potentially essential genes in B. malayi. Further incorporation of human host genome sequence data and a custom algorithm for prioritization enables us to collect and rank nearly 600 drug target candidates. Previously identified potential drug targets cluster near the top of our prioritized list, lending credibility to our methodology. Over-represented Gene Ontology terms, predicted InterPro domains, and RNAi phenotypes of C. elegans orthologs associated with the potential target pool are identified. By virtue of the selection procedure, the potential B. malayi drug targets highlight components of key processes in nematode biology such as central metabolism, molting and regulation of gene expression.

  6. Escherichia coli Global Gene Expression in Urine from Women with Urinary Tract Infection

    PubMed Central

    Rasko, David A.; Faerber, Gary J.; Mobley, Harry L. T.

    2010-01-01

    Murine models of urinary tract infection (UTI) have provided substantial data identifying uropathogenic E. coli (UPEC) virulence factors and assessing their expression in vivo. However, it is unclear how gene expression in these animal models compares to UPEC gene expression during UTI in humans. To address this, we used a UPEC strain CFT073-specific microarray to measure global gene expression in eight E. coli isolates monitored directly from the urine of eight women presenting at a clinic with bacteriuria. The resulting gene expression profiles were compared to those of the same E. coli isolates cultured statically to exponential phase in pooled, sterilized human urine ex vivo. Known fitness factors, including iron acquisition and peptide transport systems, were highly expressed during human UTI and support a model in which UPEC replicates rapidly in vivo. While these findings were often consistent with previous data obtained from the murine UTI model, host-specific differences were observed. Most strikingly, expression of type 1 fimbrial genes, which are among the most highly expressed genes during murine experimental UTI and encode an essential virulence factor for this experimental model, was undetectable in six of the eight E. coli strains from women with UTI. Despite the lack of type 1 fimbrial expression in the urine samples, these E. coli isolates were generally capable of expressing type 1 fimbriae in vitro and highly upregulated fimA upon experimental murine infection. The findings presented here provide insight into the metabolic and pathogenic profile of UPEC in urine from women with UTI and represent the first transcriptome analysis for any pathogenic E. coli during a naturally occurring infection in humans. PMID:21085611

  7. Global Gene Expression Profiling through the Complete Life Cycle of Trypanosoma vivax

    PubMed Central

    Jackson, Andrew P.; Goyard, Sophie; Xia, Dong; Foth, Bernardo J.; Sanders, Mandy; Wastling, Jonathan M.; Minoprio, Paola; Berriman, Matthew

    2015-01-01

    The parasitic flagellate Trypanosoma vivax is a cause of animal trypanosomiasis across Africa and South America. The parasite has a digenetic life cycle, passing between mammalian hosts and insect vectors, and a series of developmental forms adapted to each life cycle stage. Each point in the life cycle presents radically different challenges to parasite metabolism and physiology and distinct host interactions requiring remodeling of the parasite cell surface. Transcriptomic and proteomic studies of the related parasites T. brucei and T. congolense have shown how gene expression is regulated during their development. New methods for in vitro culture of the T. vivax insect stages have allowed us to describe global gene expression throughout the complete T. vivax life cycle for the first time. We combined transcriptomic and proteomic analysis of each life stage using RNA-seq and mass spectrometry respectively, to identify genes with patterns of preferential transcription or expression. While T. vivax conforms to a pattern of highly conserved gene expression found in other African trypanosomes, (e.g. developmental regulation of energy metabolism, restricted expression of a dominant variant antigen, and expression of ‘Fam50’ proteins in the insect mouthparts), we identified significant differences in gene expression affecting metabolism in the fly and a suite of T. vivax-specific genes with predicted cell-surface expression that are preferentially expressed in the mammal (‘Fam29, 30, 42’) or the vector (‘Fam34, 35, 43’). T. vivax differs significantly from other African trypanosomes in the developmentally-regulated proteins likely to be expressed on its cell surface and thus, in the structure of the host-parasite interface. These unique features may yet explain the species differences in life cycle and could, in the form of bloodstream-stage proteins that do not undergo antigenic variation, provide targets for therapy. PMID:26266535

  8. [Global expression analysis in uterine cervical cancer: metabolic pathways and altered genes].

    PubMed

    Vázquez-Ortíz, Guelaguetza; Piña-Sanchez, Patricia; Hidalgo, Alfredo; Lazos, Minerva; Moreno, José; Alvarado, Isabel; Cruz, Fernando; Hernández, Dulce M; Pérez-Plascencia, Carlos; Salcedo, Mauricio

    2005-01-01

    High risk human papillomavirus (HPV) infection is considered to be the most important etiological factor of Cervical Uterine Cancer. In order to determine the global expression pattern and to identify possible molecular markers of cervical cancer, cDNA arrays with probe sets complementary to 8,000 human genes were used to examine the expression profiles among 5 cell lines derived from human cervical cancer, three HPV16(+) tumor samples and three normal cervical tissues HPV(-). The levels of expression of different cellular processes were identified. Hierarchical clustering was performed and the gene expression using RT-PCR was confirmed. Two genes were found to be consistently overexpressed in invasive cervical cancer biopsies; one of them, IL-6 was previously reported to be overexpressed in cervical cancer and one novel gene, MMP10, previously not known to be related to cervical cancer. Hierarchical clustering of the expression data revealed that samples with common HPV type infection grouped together, maybe this could mean that differences between HPV types could be indirectly determined by expression profiles.

  9. Global gene expression profiling of hyperkeratotic skin lesions from inner Mongolians chronically exposed to arsenic.

    PubMed

    Bailey, Kathryn; Xia, Yajuan; Ward, William O; Knapp, Geremy; Mo, Jinyao; Mumford, Judy L; Owen, Russell D; Thai, Sheau-Fung

    2009-12-01

    The skin is an organ that is highly sensitive to chronic arsenic (As) exposure. Skin lesions such as hyperkeratoses (HKs) are common early manifestations of arsenicosis in humans. HKs can be precursor lesions of nonmelanoma skin cancers (NMSCs), but the driving forces behind their formation and how they may ultimately progress to NMSCs are unknown. The goal of this study was to examine the global gene expression profiles of As-related HKs in an effort to better understand gene expression changes that are potentially associated with early stages of As carcinogenesis. HK biopsies were removed from individuals living in an arsenicosis-endemic region in Inner Mongolia who had been exposed to high As levels in their drinking water for >20 years. Gene expression profiling was performed on RNA isolated from 7 individuals in this group and from 4 lesion-free skin samples from healthy individuals. Consistent with the pathological characteristics of the HK lesions, major functional categories and known canonical pathways represented by altered transcripts include those involved in development, differentiation, apoptosis, proliferation, and stress response. The results of this study may help define a signature profile of gene expression changes associated with long-term As exposure in the skin.

  10. Global identification of miR-373-regulated genes in breast cancer by quantitative proteomics.

    PubMed

    Yan, Guang-Rong; Xu, Song-Hui; Tan, Zi-Lu; Liu, Langxia; He, Qing-Yu

    2011-03-01

    Although microRNAs (miRNAs) have been reported to play an important role in carcinogenesis, their molecular mechanism remains largely unknown because of our limited understanding of miRNA target genes. miR-373 was found to be capable of promoting breast cancer invasion and metastasis, but only a target gene was experimentally identified on the basis of mRNA expression analysis. In this study, we used SILAC-based quantitative proteomics to globally identify the genes regulated by miR-373. Totally, 3666 proteins were identified, and 335 proteins were found to be regulated by miR-373. Among the 192 proteins that were downregulated by miR-373, 27 (14.1%) were predicted to have at least one potential match site at their 3'-UTR for miR-373 seed sequence. However, miR-373 did not affect the mRNA level of the five selected candidate targets, TXNIP, TRPS1, RABEP1, GRHL2 and HIP1, suggesting that the protein expressions were regulated by miR-373 via translational inhibition instead of mRNA degradation. Luciferase and mutation assays validated that TXNIP and RABEP1 were the direct target genes of miR-373. More than 30 proteins reported to be involved in cancer invasion and metastasis were found to be regulated by miR-373 in breast cancer for the first time.

  11. A systems level predictive model for global gene regulation of methanogenesis in a hydrogenotrophic methanogen

    PubMed Central

    Yoon, Sung Ho; Turkarslan, Serdar; Reiss, David J.; Pan, Min; Burn, June A.; Costa, Kyle C.; Lie, Thomas J.; Slagel, Joseph; Moritz, Robert L.; Hackett, Murray; Leigh, John A.; Baliga, Nitin S.

    2013-01-01

    Methanogens catalyze the critical methane-producing step (called methanogenesis) in the anaerobic decomposition of organic matter. Here, we present the first predictive model of global gene regulation of methanogenesis in a hydrogenotrophic methanogen, Methanococcus maripaludis. We generated a comprehensive list of genes (protein-coding and noncoding) for M. maripaludis through integrated analysis of the transcriptome structure and a newly constructed Peptide Atlas. The environment and gene-regulatory influence network (EGRIN) model of the strain was constructed from a compendium of transcriptome data that was collected over 58 different steady-state and time-course experiments that were performed in chemostats or batch cultures under a spectrum of environmental perturbations that modulated methanogenesis. Analyses of the EGRIN model have revealed novel components of methanogenesis that included at least three additional protein-coding genes of previously unknown function as well as one noncoding RNA. We discovered that at least five regulatory mechanisms act in a combinatorial scheme to intercoordinate key steps of methanogenesis with different processes such as motility, ATP biosynthesis, and carbon assimilation. Through a combination of genetic and environmental perturbation experiments we have validated the EGRIN-predicted role of two novel transcription factors in the regulation of phosphate-dependent repression of formate dehydrogenase—a key enzyme in the methanogenesis pathway. The EGRIN model demonstrates regulatory affiliations within methanogenesis as well as between methanogenesis and other cellular functions. PMID:24089473

  12. Gene expression during the first 28 days of axolotl limb regeneration I: Experimental design and global analysis of gene expression

    PubMed Central

    Palumbo, Alex; Nagarajan, Radha; Gardiner, David M.; Muneoka, Ken; Stromberg, Arnold J.; Athippozhy, Antony T.

    2015-01-01

    Abstract While it is appreciated that global gene expression analyses can provide novel insights about complex biological processes, experiments are generally insufficiently powered to achieve this goal. Here we report the results of a robust microarray experiment of axolotl forelimb regeneration. At each of 20 post‐amputation time points, we estimated gene expression for 10 replicate RNA samples that were isolated from 1 mm of heterogeneous tissue collected from the distal limb tip. We show that the limb transcription program diverges progressively with time from the non‐injured state, and divergence among time adjacent samples is mostly gradual. However, punctuated episodes of transcription were identified for five intervals of time, with four of these coinciding with well‐described stages of limb regeneration—amputation, early bud, late bud, and pallet. The results suggest that regeneration is highly temporally structured and regulated by mechanisms that function within narrow windows of time to coordinate transcription within and across cell types of the regenerating limb. Our results provide an integrative framework for hypothesis generation using this complex and highly informative data set. PMID:27168937

  13. Mining regulatory network connections by ranking transcription factor target genes using time series expression data.

    PubMed

    Honkela, Antti; Rattray, Magnus; Lawrence, Neil D

    2013-01-01

    Reverse engineering the gene regulatory network is challenging because the amount of available data is very limited compared to the complexity of the underlying network. We present a technique addressing this problem through focussing on a more limited problem: inferring direct targets of a transcription factor from short expression time series. The method is based on combining Gaussian process priors and ordinary differential equation models allowing inference on limited potentially unevenly sampled data. The method is implemented as an R/Bioconductor package, and it is demonstrated by ranking candidate targets of the p53 tumour suppressor.

  14. Triterpenoid saponin biosynthetic pathway profiling and candidate gene mining of the Ilex asprella root using RNA-Seq.

    PubMed

    Zheng, Xiasheng; Xu, Hui; Ma, Xinye; Zhan, Ruoting; Chen, Weiwen

    2014-04-09

    Ilex asprella, which contains abundant α-amyrin type triterpenoid saponins, is an anti-influenza herbal drug widely used in south China. In this work, we first analysed the transcriptome of the I. asprella root using RNA-Seq, which provided a dataset for functional gene mining. mRNA was isolated from the total RNA of the I. asprella root and reverse-transcribed into cDNA. Then, the cDNA library was sequenced using an Illumina HiSeq™ 2000, which generated 55,028,452 clean reads. De novo assembly of these reads generated 51,865 unigenes, in which 39,269 unigenes were annotated (75.71% yield). According to the structures of the triterpenoid saponins of I. asprella, a putative biosynthetic pathway downstream of 2,3-oxidosqualene was proposed and candidate unigenes in the transcriptome data that were potentially involved in the pathway were screened using homology-based BLAST and phylogenetic analysis. Further amplification and functional analysis of these putative unigenes will provide insight into the biosynthesis of Ilex triterpenoid saponins.

  15. Triterpenoid Saponin Biosynthetic Pathway Profiling and Candidate Gene Mining of the Ilex asprella Root Using RNA-Seq

    PubMed Central

    Zheng, Xiasheng; Xu, Hui; Ma, Xinye; Zhan, Ruoting; Chen, Weiwen

    2014-01-01

    Ilex asprella, which contains abundant α-amyrin type triterpenoid saponins, is an anti-influenza herbal drug widely used in south China. In this work, we first analysed the transcriptome of the I. asprella root using RNA-Seq, which provided a dataset for functional gene mining. mRNA was isolated from the total RNA of the I. asprella root and reverse-transcribed into cDNA. Then, the cDNA library was sequenced using an Illumina HiSeq™ 2000, which generated 55,028,452 clean reads. De novo assembly of these reads generated 51,865 unigenes, in which 39,269 unigenes were annotated (75.71% yield). According to the structures of the triterpenoid saponins of I. asprella, a putative biosynthetic pathway downstream of 2,3-oxidosqualene was proposed and candidate unigenes in the transcriptome data that were potentially involved in the pathway were screened using homology-based BLAST and phylogenetic analysis. Further amplification and functional analysis of these putative unigenes will provide insight into the biosynthesis of Ilex triterpenoid saponins. PMID:24722569

  16. Global Gene Expression Patterns in Clostridium thermocellum as Determined by Microarray Analysis of Chemostat Cultures on Cellulose or Cellobiose▿ †

    PubMed Central

    Riederer, Allison; Takasuka, Taichi E.; Makino, Shin-ichi; Stevenson, David M.; Bukhman, Yury V.; Elsen, Nathaniel L.; Fox, Brian G.

    2011-01-01

    A microarray study of chemostat growth on insoluble cellulose or soluble cellobiose has provided substantial new information on Clostridium thermocellum gene expression. This is the first comprehensive examination of gene expression in C. thermocellum under defined growth conditions. Expression was detected from 2,846 of 3,189 genes, and regression analysis revealed 348 genes whose changes in expression patterns were growth rate and/or substrate dependent. Successfully modeled genes included those for scaffoldin and cellulosomal enzymes, intracellular metabolic enzymes, transcriptional regulators, sigma factors, signal transducers, transporters, and hypothetical proteins. Unique genes encoding glycolytic pathway and ethanol fermentation enzymes expressed at high levels simultaneously with previously established maximal ethanol production were also identified. Ranking of normalized expression intensities revealed significant changes in transcriptional levels of these genes. The pattern of expression of transcriptional regulators, sigma factors, and signal transducers indicates that response to growth rate is the dominant global mechanism used for control of gene expression in C. thermocellum. PMID:21169455

  17. Mining of hemicellulose and lignin degrading genes from differentially enriched methane producing microbial community.

    PubMed

    Pandit, Prabhakar D; Gulhane, Madhuri K; Khardenavis, Anshuman A; Purohit, Hemant J

    2016-09-01

    Study creates a scenario for enrichment and selection of ligno-hemicellulose degrading genotypes with anaerobic bioreactor as a model using rice straw, vegetable waste and food waste as substrates. Relative discrimination analysis showed that the hydrolytic pathways and associated microbial communities for ligno-hemicellulose degradation were dominatingly colonized with rice straw as substrate. The dominating bacteria were Caldicellulosiruptor, Fervidobacterium, Cytophaga, Ruminococcus, Thermotoga associated with hemicellulose degradation and Burkholderia, Pandorea, Sphingomonas, Spirochaeta, Pseudomonas for lignocellulose hydrolysis. This was further supported by the abundance of anaerobic aromatic compound degrading genes along with genes for xylanase and xylosidase in rice straw enriched community. The metagenome analysis data was validated by evaluation of the biochemical methane potential for these substrates. Food waste being most amenable substrate yielded 1410mL of biogas/gVS added whereas, biogas yield of 1160mL/gVS and 1080mL/gVS was observed in presence of vegetable waste and rice straw respectively. PMID:27323244

  18. Global Analysis of Gene Expression Profiles in Developing Physic Nut (Jatropha curcas L.) Seeds

    PubMed Central

    Jiang, Huawu; Wu, Pingzhi; Zhang, Sheng; Song, Chi; Chen, Yaping; Li, Meiru; Jia, Yongxia; Fang, Xiaohua; Chen, Fan; Wu, Guojiang

    2012-01-01

    Background Physic nut (Jatropha curcas L.) is an oilseed plant species with high potential utility as a biofuel. Furthermore, following recent sequencing of its genome and the availability of expressed sequence tag (EST) libraries, it is a valuable model plant for studying carbon assimilation in endosperms of oilseed plants. There have been several transcriptomic analyses of developing physic nut seeds using ESTs, but they have provided limited information on the accumulation of stored resources in the seeds. Methodology/Principal Findings We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of developing physic nut seeds 14, 19, 25, 29, 35, 41, and 45 days after pollination (DAP). The acquired profiles reveal the key genes, and their expression timeframes, involved in major metabolic processes including: carbon flow, starch metabolism, and synthesis of storage lipids and proteins in the developing seeds. The main period of storage reserves synthesis in the seeds appears to be 29–41 DAP, and the fatty acid composition of the developing seeds is consistent with relative expression levels of different isoforms of acyl-ACP thioesterase and fatty acid desaturase genes. Several transcription factor genes whose expression coincides with storage reserve deposition correspond to those known to regulate the process in Arabidopsis. Conclusions/Significance The results will facilitate searches for genes that influence de novo lipid synthesis, accumulation and their regulatory networks in developing physic nut seeds, and other oil seeds. Thus, they will be helpful in attempts to modify these plants for efficient biofuel production. PMID:22574177

  19. Global gene expression in channel catfish after vaccination with an attenuated Edwardsiella ictaluri.

    PubMed

    Pridgeon, Julia W; Yeh, Hung-Yueh; Shoemaker, Craig A; Mu, Xingjiang; Klesius, Phillip H

    2012-04-01

    To understand the global gene expression in channel catfish after immersion vaccination with an attenuated Edwardsiella ictaluri (AquaVac-ESC™), microarray analysis of 65,182 UniGene transcripts was performed. With a filter of false-discovery rate less than 0.05 and fold change greater than 2, a total of 52 unique transcripts were found to be upregulated in vaccinated fish at 48 h post vaccination, whereas a total of 129 were downregulated. The 52 upregulated transcripts represent genes with putative functions in the following seven major categories: (1) hypothetical (25%); (2) novel (23%); (3) immune response (17%); (4) signal transduction (15%); (5) cell structure (8%); (6) metabolism (4%); and (7) others (8%). The 129 downregulated transcripts represent genes with putative functions in the following ten major categories: (1) novel (25%); (2) immune response (23%); (3) hypothetical (12%); (4) metabolism (10%); (5) signal transduction (7%); (6) protein synthesis (6.2%); (7) cell structure (5%); (8) apoptosis (3%); (9) transcription/translation (2%); and (10) others (6%). Microarray analysis revealed that apolipoprotein A-I was upregulated the most (8.5 fold, P = 0.011) at 48 h post vaccination whereas a novel protein (accession no. CV995854) was downregulated the most (342 fold, P = 0.001). Differential regulation of several randomly selected transcripts in vaccinated fish was also validated by quantitative PCR. Our results suggest that these differentially regulated genes elicited by the vaccination might play important roles in the protection of channel catfish against E. ictaluri.

  20. Binding motifs in bacterial gene promoters modulate transcriptional effect of global regulators

    SciTech Connect

    Leuze, Michael Rex; Karpinets, Tatiana V; Syed, Mustafa H; Beliaev, Alexander S; Uberbacher, Edward C

    2012-01-01

    Bacterial gene regulation involves transcription factors (TFs) that influence the expression of many genes. Global regulators, including CRP (cAMP Receptor Protein), ArcA, and FNR, can modulate the transcriptional activity of multiple operons. The similarity of a regulatory element s sequence to a TF s consensus binding site (BS) and the position of the regulatory element in an operon promoter are considered the most important determinants of this TF s regulatory influence. In this study we explore the hypothesis that the number of TFBS half-sites (where a half-site is one half of the palindromic BS consensus sequence, which we shall refer to as a binding motif or a BM) of a global regulator in an operon s promoter plays an important role in the operon s transcriptional regulation. We examine empirical data from transcriptional profiling of the CRP regulon in Shewanella oneidenses MR 1 and Escherichia coli, and of the ArcA regulon in S. oneidenses MR 1. We compare the power of CRP BM counts and of full, symmetrical CRP TFBS characteristics, namely similarity to consensus and location, to predict CRP-induced transcriptional activity. We find that CRP BM counts have a nonlinear effect on CRP-dependent transcriptional activity and predict this activity better than full-length TFBS quality or location. Regression analysis indicates that IHF (Integration Host Factor) and ArcA have synergistic effects on CRP-induced gene transcription, positive and negative, respectively. Based on these results, we propose that the fine-tuning of bacterial transcriptional activity by CRP may involves not only the bending of the operon promoter, facilitated by CRP in cooperation with the histone-like protein IHF, but also the cumulative binding affinity of multiple weak BMs.

  1. Mapping global vulnerability index in mining sectors: A case study Moulares-Redayef aquifer system, southwestern Tunisia

    NASA Astrophysics Data System (ADS)

    Khelif, Nadia; Jmal, Ikram; Bouri, Salem

    2016-09-01

    Contrary to the DRASTIC model grouping together the saturated and unsaturated zones to compute a global intrinsic vulnerability index, the global vulnerability index method incorporates both hydrogeological and hydrochemical data for a comprehensive index mapping for the saturated zones. This concept depends on the behavior and the uses of the groundwater. The main aim of this study is to propose a scientific basis for sustainable land use planning and groundwater management of the Moulares-Reayef aquifer, located in Southwestern Tunisia. The overexploitation of this aquifer causes the threat of groundwater quality by various sources of pollution. The global vulnerability index was applied in the Moulares-Reayef aquifer. The results show that the most favorable zones to pollutant percolation are situated along the wadis (Tabaddit, Zallaz, Berka, …) which are drained by continuous discharges. The global vulnerability values were correlated with nitrates values for validation. It revealed a significant correlation showing that high values of nitrates occurred in highly vulnerable zones with a value of 0.69 for the Pearson coefficient. The global vulnerability evaluation shows that the aquifer is characterized by high vertical vulnerability and high susceptibility.

  2. PTRcombiner: mining combinatorial regulation of gene expression from post-transcriptional interaction maps

    PubMed Central

    2014-01-01

    Background The progress in mapping RNA-protein and RNA-RNA interactions at the transcriptome-wide level paves the way to decipher possible combinatorial patterns embedded in post-transcriptional regulation of gene expression. Results Here we propose an innovative computational tool to extract clusters of mRNA trans-acting co-regulators (RNA binding proteins and non-coding RNAs) from pairwise interaction annotations. In addition the tool allows to analyze the binding site similarity of co-regulators belonging to the same cluster, given their positional binding information. The tool has been tested on experimental collections of human and yeast interactions, identifying modules that coordinate functionally related messages. Conclusions This tool is an original attempt to uncover combinatorial patterns using all the post-transcriptional interaction data available so far. PTRcombiner is available at http://disi.unitn.it/~passerini/software/PTRcombiner/. PMID:24758252

  3. Differentially expressed genes in Bordetella pertussis strains belonging to a lineage which recently spread globally.

    PubMed

    de Gouw, Daan; Hermans, Peter W M; Bootsma, Hester J; Zomer, Aldert; Heuvelman, Kees; Diavatopoulos, Dimitri A; Mooi, Frits R

    2014-01-01

    Pertussis is a highly contagious, acute respiratory disease in humans caused by the Gram-negative pathogen Bordetella pertussis. Pertussis has resurged in the face of intensive vaccination and this has coincided with the emergence of strains carrying a particular allele for the pertussis toxin promoter, ptxP3, which is associated with higher levels of pertussis toxin (Ptx) production. Within 10 to 20 years, ptxP3 strains have nearly completely replaced the previously dominant ptxP1 strains resulting in a worldwide selective sweep. In order to identify B. pertussis genes associated with the selective sweep, we compared the expression of genes in ptxP1 and ptxP3 strains that are under control of the Bordetella master virulence regulatory locus (bvgASR). The BvgAS proteins comprise a two component sensory transduction system which is regulated by temperature, nicotinic acid and sulfate. By increasing the sulfate concentration, it is possible to change the phase of B. pertussis from virulent to avirulent. Until recently, the only distinctive phenotype of ptxP3 strains was a higher Ptx production. Here we identify additional phenotypic differences between ptxP1 and ptxP3 strains which may have contributed to its global spread by comparing global transcriptional responses under sulfate-modulating conditions. We show that ptxP3 strains are less sensitive to sulfate-mediated gene suppression, resulting in an increased production of the vaccine antigens pertactin (Prn) and Ptx and a number of other virulence genes, including a type III secretion toxin, Vag8, a protein involved in complement resistance, and lpxE involved in lipid A modification. Furthermore, enhanced expression of the vaccine antigens Ptx and Prn by ptxP3 strains was confirmed at the protein level. Identification of genes differentially expressed between ptxP1 and ptxP3 strains may elucidate how B. pertussis has adapted to vaccination and allow the improvement of pertussis vaccines by identifying novel

  4. Differentially Expressed Genes in Bordetella pertussis Strains Belonging to a Lineage Which Recently Spread Globally

    PubMed Central

    de Gouw, Daan; Hermans, Peter W. M.; Bootsma, Hester J.; Zomer, Aldert; Heuvelman, Kees; Diavatopoulos, Dimitri A.; Mooi, Frits R.

    2014-01-01

    Pertussis is a highly contagious, acute respiratory disease in humans caused by the Gram-negative pathogen Bordetella pertussis. Pertussis has resurged in the face of intensive vaccination and this has coincided with the emergence of strains carrying a particular allele for the pertussis toxin promoter, ptxP3, which is associated with higher levels of pertussis toxin (Ptx) production. Within 10 to 20 years, ptxP3 strains have nearly completely replaced the previously dominant ptxP1 strains resulting in a worldwide selective sweep. In order to identify B. pertussis genes associated with the selective sweep, we compared the expression of genes in ptxP1 and ptxP3 strains that are under control of the Bordetella master virulence regulatory locus (bvgASR). The BvgAS proteins comprise a two component sensory transduction system which is regulated by temperature, nicotinic acid and sulfate. By increasing the sulfate concentration, it is possible to change the phase of B. pertussis from virulent to avirulent. Until recently, the only distinctive phenotype of ptxP3 strains was a higher Ptx production. Here we identify additional phenotypic differences between ptxP1 and ptxP3 strains which may have contributed to its global spread by comparing global transcriptional responses under sulfate-modulating conditions. We show that ptxP3 strains are less sensitive to sulfate-mediated gene suppression, resulting in an increased production of the vaccine antigens pertactin (Prn) and Ptx and a number of other virulence genes, including a type III secretion toxin, Vag8, a protein involved in complement resistance, and lpxE involved in lipid A modification. Furthermore, enhanced expression of the vaccine antigens Ptx and Prn by ptxP3 strains was confirmed at the protein level. Identification of genes differentially expressed between ptxP1 and ptxP3 strains may elucidate how B. pertussis has adapted to vaccination and allow the improvement of pertussis vaccines by identifying novel

  5. The global gene expression response of Escherichia coli to L-phenylalanine.

    PubMed

    Polen, T; Krämer, M; Bongaerts, J; Wubbolts, M; Wendisch, V F

    2005-02-01

    We investigated the global gene expression changes of Escherichia coli due to the presence of different concentrations of phenylalanine or shikimate in the growth medium. The response to 0.5 g l(-1) phenylalanine primarily reflected a perturbed aromatic amino acid metabolism, in particular due to TyrR-mediated regulation. The addition of 5g l(-1) phenylalanine reduced the growth rate by half and elicited a great number of likely indirect effects on genes regulated in response to changed pH, nitrogen or carbon availability. Consistent with the observed gene expression changes, supplementation with shikimate, tyrosine and tryptophan relieved growth inhibition by phenylalanine. In contrast to the wild-type, a tyrR disruption strain showed increased expression of pckA and of tktB in the presence of phenylalanine, but its growth was not affected by phenylalanine at the concentrations tested. The absence of growth inhibition by phenylalanine suggested that at high phenylalanine concentrations TyrR-defective strains might perform better in phenylalanine production. PMID:15639085

  6. Global prevalence and distribution of genes and microorganisms involved in mercury methylation

    PubMed Central

    Podar, Mircea; Gilmour, Cynthia C.; Brandt, Craig C.; Soren, Allyson; Brown, Steven D.; Crable, Bryan R.; Palumbo, Anthony V.; Somenahally, Anil C.; Elias, Dwayne A.

    2015-01-01

    Mercury (Hg) methylation produces the neurotoxic, highly bioaccumulative methylmercury (MeHg). The highly conserved nature of the recently identified Hg methylation genes hgcAB provides a foundation for broadly evaluating spatial and niche-specific patterns of microbial Hg methylation potential in nature. We queried hgcAB diversity and distribution in >3500 publicly available microbial metagenomes, encompassing a broad range of environments and generating a new global view of Hg methylation potential. The hgcAB genes were found in nearly all anaerobic (but not aerobic) environments, including oxygenated layers of the open ocean. Critically, hgcAB was effectively absent in ~1500 human and mammalian microbiomes, suggesting a low risk of endogenous MeHg production. New potential methylation habitats were identified, including invertebrate digestive tracts, thawing permafrost soils, coastal “dead zones,” soils, sediments, and extreme environments, suggesting multiple routes for MeHg entry into food webs. Several new taxonomic groups capable of methylating Hg emerged, including lineages having no cultured representatives. Phylogenetic analysis points to an evolutionary relationship between hgcA and genes encoding corrinoid iron-sulfur proteins functioning in the ancient Wood-Ljungdahl carbon fixation pathway, suggesting that methanogenic Archaea may have been the first to perform these biotransformations. PMID:26601305

  7. Global prevalence and distribution of genes and microorganisms involved in mercury methylation.

    PubMed

    Podar, Mircea; Gilmour, Cynthia C; Brandt, Craig C; Soren, Allyson; Brown, Steven D; Crable, Bryan R; Palumbo, Anthony V; Somenahally, Anil C; Elias, Dwayne A

    2015-10-01

    Mercury (Hg) methylation produces the neurotoxic, highly bioaccumulative methylmercury (MeHg). The highly conserved nature of the recently identified Hg methylation genes hgcAB provides a foundation for broadly evaluating spatial and niche-specific patterns of microbial Hg methylation potential in nature. We queried hgcAB diversity and distribution in >3500 publicly available microbial metagenomes, encompassing a broad range of environments and generating a new global view of Hg methylation potential. The hgcAB genes were found in nearly all anaerobic (but not aerobic) environments, including oxygenated layers of the open ocean. Critically, hgcAB was effectively absent in ~1500 human and mammalian microbiomes, suggesting a low risk of endogenous MeHg production. New potential methylation habitats were identified, including invertebrate digestive tracts, thawing permafrost soils, coastal "dead zones," soils, sediments, and extreme environments, suggesting multiple routes for MeHg entry into food webs. Several new taxonomic groups capable of methylating Hg emerged, including lineages having no cultured representatives. Phylogenetic analysis points to an evolutionary relationship between hgcA and genes encoding corrinoid iron-sulfur proteins functioning in the ancient Wood-Ljungdahl carbon fixation pathway, suggesting that methanogenic Archaea may have been the first to perform these biotransformations. PMID:26601305

  8. Global control of motor neuron topography mediated by the repressive actions of a single hox gene.

    PubMed

    Jung, Heekyung; Lacombe, Julie; Mazzoni, Esteban O; Liem, Karel F; Grinstein, Jonathan; Mahony, Shaun; Mukhopadhyay, Debnath; Gifford, David K; Young, Richard A; Anderson, Kathryn V; Wichterle, Hynek; Dasen, Jeremy S

    2010-09-01

    In the developing spinal cord, regional and combinatorial activities of Hox transcription factors are critical in controlling motor neuron fates along the rostrocaudal axis, exemplified by the precise pattern of limb innervation by more than fifty Hox-dependent motor pools. The mechanisms by which motor neuron diversity is constrained to limb levels are, however, not well understood. We show that a single Hox gene, Hoxc9, has an essential role in organizing the motor system through global repressive activities. Hoxc9 is required for the generation of thoracic motor columns, and in its absence, neurons acquire the fates of limb-innervating populations. Unexpectedly, multiple Hox genes are derepressed in Hoxc9 mutants, leading to motor pool disorganization and alterations in the connections by thoracic and forelimb-level subtypes. Genome-wide analysis of Hoxc9 binding suggests that this mode of repression is mediated by direct interactions with Hox regulatory elements, independent of chromatin marks typically associated with repressed Hox genes.

  9. Histopathologic Alterations Associated with Global Gene Expression Due to Chronic Dietary TCDD Exposure in Juvenile Zebrafish

    PubMed Central

    Liu, Qing; Spitsbergen, Jan M.; Cariou, Ronan; Huang, Chun-Yuan; Jiang, Nan; Goetz, Giles; Hutz, Reinhold J.; Tonellato, Peter J.; Carvan, Michael J.

    2014-01-01

    The goal of this project was to investigate the effects and possible developmental disease implication of chronic dietary TCDD exposure on global gene expression anchored to histopathologic analysis in juvenile zebrafish by functional genomic, histopathologic and analytic chemistry methods. Specifically, juvenile zebrafish were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb, and fish were sampled following 0, 7, 14, 28 and 42 d after initiation of the exposure. TCDD accumulated in a dose- and time-dependent manner and 100 ppb TCDD caused TCDD accumulation in female (15.49 ppb) and male (18.04 ppb) fish at 28 d post exposure. Dietary TCDD caused multiple lesions in liver, kidney, intestine and ovary of zebrafish and functional dysregulation such as depletion of glycogen in liver, retrobulbar edema, degeneration of nasal neurosensory epithelium, underdevelopment of intestine, and diminution in the fraction of ovarian follicles containing vitellogenic oocytes. Importantly, lesions in nasal epithelium and evidence of endocrine disruption based on alternatively spliced vasa transcripts are two novel and significant results of this study. Microarray gene expression analysis comparing vehicle control to dietary TCDD revealed dysregulated genes involved in pathways associated with cardiac necrosis/cell death, cardiac fibrosis, renal necrosis/cell death and liver necrosis/cell death. These baseline toxicological effects provide evidence for the potential mechanisms of developmental dysfunctions induced by TCDD and vasa as a biomarker for ovarian developmental disruption. PMID:24988445

  10. Global Gene Expression Analysis of Long-Term Stationary Phase Effects in E. coli K12 MG1655

    PubMed Central

    Arunasri, Kotakonda; Adil, Mohammed; Khan, Pathan Akbar Ali; Shivaji, Sisinthy

    2014-01-01

    Global gene expression was monitored in long-term stationary phase (LSP) cells of E. coli K12 MG1655 and compared with stationary phase (SP) cells that were sub-cultured without prolonged delay to get an insight into the survival strategies of LSP cells. The experiments were carried out using both LB medium and LB supplemented with 10% of glycerol. In both the media the LSP cells showed decreased growth rate compared to SP cells. DNA microarray analysis of LSP cells in both the media resulted in the up- and down-regulation of several genes in LSP cells compared to their respective SP cells in the corresponding media. In LSP cells grown in LB 204 genes whereas cells grown in LB plus glycerol 321 genes were differentially regulated compared to the SP cells. Comparison of these differentially regulated genes indicated that irrespective of the medium used for growth in LSP cells expression of 95 genes (22 genes up-regulated and 73 down-regulated) were differentially regulated. These 95 genes could be associated with LSP status of the cells and are likely to influence survival and growth characteristics of LSP cells. This is indeed so since the up- and down-regulated genes include genes that protect E. coli LSP cells from stationary phase stress and genes that would help to recover from stress when transferred into fresh medium. The growth phenotype in LSP cells could be attributed to up-regulation of genes coding for insertion sequences that confer beneficial effects during starvation, genes coding for putative transposases and simultaneous down-regulation of genes coding for ribosomal protein synthesis, transport-related genes, non-coding RNA genes and metabolic genes. As yet we still do not know the role of several unknown genes and genes coding for hypothetical proteins which are either up- or down-regulated in LSP cells compared to SP cells. PMID:24858919

  11. Mining and gene ontology based annotation of SSR markers from expressed sequence tags of Humulus lupulus.

    PubMed

    Singh, Swati; Gupta, Sanchita; Mani, Ashutosh; Chaturvedi, Anoop

    2012-01-01

    Humulus lupulus is commonly known as hops, a member of the family moraceae. Currently many projects are underway leading to the accumulation of voluminous genomic and expressed sequence tag sequences in public databases. The genetically characterized domains in these databases are limited due to non-availability of reliable molecular markers. The large data of EST sequences are available in hops. The simple sequence repeat markers extracted from EST data are used as molecular markers for genetic characterization, in the present study. 25,495 EST sequences were examined and assembled to get full-length sequences. Maximum frequency distribution was shown by mononucleotide SSR motifs i.e. 60.44% in contig and 62.16% in singleton where as minimum frequency are observed for hexanucleotide SSR in contig (0.09%) and pentanucleotide SSR in singletons (0.12%). Maximum trinucleotide motifs code for Glutamic acid (GAA) while AT/TA were the most frequent repeat of dinucleotide SSRs. Flanking primer pairs were designed in-silico for the SSR containing sequences. Functional categorization of SSRs containing sequences was done through gene ontology terms like biological process, cellular component and molecular function.

  12. Global SUMO Proteome Responses Guide Gene Regulation, mRNA Biogenesis, and Plant Stress Responses

    PubMed Central

    Mazur, Magdalena J.; van den Burg, Harrold A.

    2012-01-01

    Small Ubiquitin-like MOdifier (SUMO) is a key regulator of abiotic stress, disease resistance, and development in plants. The identification of >350 plant SUMO targets has revealed many processes modulated by SUMO and potential consequences of SUMO on its targets. Importantly, highly related proteins are SUMO-modified in plants, yeast, and metazoans. Overlapping SUMO targets include heat-shock proteins (HSPs), transcription regulators, histones, histone-modifying enzymes, proteins involved in DNA damage repair, but also proteins involved in mRNA biogenesis and nucleo-cytoplasmic transport. Proteomics studies indicate key roles for SUMO in gene repression by controlling histone (de)acetylation activity at genomic loci. The responsible heavily sumoylated transcriptional repressor complexes are recruited by plant transcription factors (TFs) containing an (ERF)-associated Amphiphilic Repression (EAR) motif. These TFs are not necessarily themselves a SUMO target. Conversely, SUMO acetylation (Ac) prevents binding of downstream partners by blocking binding of their SUMO-interaction peptide motifs to Ac-SUMO. In addition, SUMO acetylation has emerged as a mechanism to recruit specifically bromodomains. Bromodomains are generally linked with gene activation. These findings strengthen the idea of a bi-directional sumo-acetylation switch in gene regulation. Quantitative proteomics has highlighted that global sumoylation provides a dynamic response to protein damage involving SUMO chain-mediated protein degradation, but also SUMO E3 ligase-dependent transcription of HSP genes. With these insights in SUMO function and novel technical advancements, we can now study SUMO dynamics in responses to (a)biotic stress in plants. PMID:23060889

  13. MS/MS-based networking and peptidogenomics guided genome mining revealed the stenothricin gene cluster in Streptomyces roseosporus

    PubMed Central

    Liu, Wei-Ting; Lamsa, Anne; Wong, Weng Ruh; Boudreau, Paul D.; Kersten, Roland; Peng, Yao; Moree, Wilna J.; Duggan, Brendan M.; Moore, Bradley S.; Gerwick, William H.; Linington, Roger G.; Pogliano, Kit; Dorrestein, Pieter C.

    2014-01-01

    Most (75%) of the anti-infectives that save countless lives and enormously improve quality of life originate from microbes found in nature. Herein, we described a global visualization of the detectable molecules produced from a single microorganism, which we define as the ‘molecular network’ of that organism, followed by studies to characterize the cellular effects of antibacterial molecules. We demonstrate that Streptomyces roseosporus produces at least four non-ribosomal peptide synthetase-derived molecular families and their gene subnetworks (daptomycin, arylomycin, napsamycin and stenothricin) were identified with different modes of action. A number of previously unreported analogs involving truncation, glycosylation, hydrolysis and biosynthetic intermediates and/or shunt products were also captured and visualized by creation of a map through MS/MS networking. The diversity of antibacterial compounds produced by S. roseosporus highlights the importance of developing new approaches to characterize the molecular capacity of an organism in a more global manner. This allows one to more deeply interrogate the biosynthetic capacities of microorganisms with the goal to streamline the discovery pipeline for biotechnological applications in agriculture and medicine. This is a contribution to a special issue to honor Chris Walsh’s amazing career. PMID:24149839

  14. Metagenomic mining for microbiologists.

    PubMed

    Delmont, Tom O; Malandain, Cedric; Prestat, Emmanuel; Larose, Catherine; Monier, Jean-Michel; Simonet, Pascal; Vogel, Timothy M

    2011-12-01

    Microbial ecologists can now start digging into the accumulating mountains of metagenomic data to uncover the occurrence of functional genes and their correlations to microbial community members. Limitations and biases in DNA extraction and sequencing technologies impact sequence distributions, and therefore, have to be considered. However, when comparing metagenomes from widely differing environments, these fluctuations have a relatively minor role in microbial community discrimination. As a consequence, any functional gene or species distribution pattern can be compared among metagenomes originating from various environments and projects. In particular, global comparisons would help to define ecosystem specificities, such as involvement and response to climate change (for example, carbon and nitrogen cycle), human health risks (eg, presence of pathogen species, toxin genes and viruses) and biodegradation capacities. Although not all scientists have easy access to high-throughput sequencing technologies, they do have access to the sequences that have been deposited in databases, and therefore, can begin to intensively mine these metagenomic data to generate hypotheses that can be validated experimentally. Information about metabolic functions and microbial species compositions can already be compared among metagenomes from different ecosystems. These comparisons add to our understanding about microbial adaptation and the role of specific microbes in different ecosystems. Concurrent with the rapid growth of sequencing technologies, we have entered a new age of microbial ecology, which will enable researchers to experimentally confirm putative relationships between microbial functions and community structures.

  15. Apomictic and Sexual Ovules of Boechera Display Heterochronic Global Gene Expression Patterns[C][W][OA

    PubMed Central

    Sharbel, Timothy F.; Voigt, Marie-Luise; Corral, José M.; Galla, Giulio; Kumlehn, Jochen; Klukas, Christian; Schreiber, Falk; Vogel, Heiko; Rotter, Björn

    2010-01-01

    We have compared the transcriptomic profiles of microdissected live ovules at four developmental stages between a diploid sexual and diploid apomictic Boechera. We sequenced >2 million SuperSAGE tags and identified (1) heterochronic tags (n = 595) that demonstrated significantly different patterns of expression between sexual and apomictic ovules across all developmental stages, (2) stage-specific tags (n = 577) that were found in a single developmental stage and differentially expressed between the sexual and apomictic ovules, and (3) sex-specific (n = 237) and apomixis-specific (n = 1106) tags that were found in all four developmental stages but in only one reproductive mode. Most heterochronic and stage-specific tags were significantly downregulated during early apomictic ovule development, and 110 were associated with reproduction. By contrast, most late stage-specific tags were upregulated in the apomictic ovules, likely the result of increased gene copy number in apomictic (hexaploid) versus sexual (triploid) endosperm or of parthenogenesis. Finally, we show that apomixis-specific gene expression is characterized by a significant overrepresentation of transcription factor activity. We hypothesize that apomeiosis is associated with global downregulation at the megaspore mother cell stage. As the diploid apomict analyzed here is an ancient hybrid, these data are consistent with the postulated link between hybridization and asexuality and provide a hypothesis for multiple evolutionary origins of apomixis in the genus Boechera. PMID:20305122

  16. Global prevalence and distribution of genes and microorganisms involved in mercury methylation

    DOE PAGES

    Podar, Mircea; Gilmour, C. C.; Brandt, Craig C.; Soren, Allyson; Brown, Steven D.; Crable, Bryan R.; Palumbo, Anthony Vito; Somenahally, Anil C.; Elias, Dwayne A.

    2015-10-09

    Mercury methylation produces the neurotoxic, highly bioaccumulative methylmercury (MeHg). Recent identification of the methylation genes (hgcAB) provides the foundation for broadly evaluating microbial Hg-methylation potential in nature without making explicit rate measurements. We first queried hgcAB diversity and distribution in all available microbial metagenomes, encompassing most environments. The genes were found in nearly all anaerobic, but not in aerobic, environments including oxygenated layers of the open ocean. Critically, hgcAB was effectively absent in ~1500 human microbiomes, suggesting a low risk of endogenous MeHg production. New potential methylation habitats were identified, including invertebrate guts, thawing permafrost, coastal dead zones, soils, sediments,more » and extreme environments, suggesting multiple routes for MeHg entry into food webs. Several new taxonomic groups potentially capable of Hg-methylation emerged, including lineages having no cultured representatives. We then begin to address long-standing evolutionary questions about Hg-methylation and ancient carbon fixation mechanisms while generating a new global view of Hg-methylation potential.« less

  17. Global prevalence and distribution of genes and microorganisms involved in mercury methylation

    SciTech Connect

    Podar, Mircea; Gilmour, C. C.; Brandt, Craig C.; Soren, Allyson; Brown, Steven D.; Crable, Bryan R.; Palumbo, Anthony Vito; Somenahally, Anil C.; Elias, Dwayne A.

    2015-10-09

    Mercury methylation produces the neurotoxic, highly bioaccumulative methylmercury (MeHg). Recent identification of the methylation genes (hgcAB) provides the foundation for broadly evaluating microbial Hg-methylation potential in nature without making explicit rate measurements. We first queried hgcAB diversity and distribution in all available microbial metagenomes, encompassing most environments. The genes were found in nearly all anaerobic, but not in aerobic, environments including oxygenated layers of the open ocean. Critically, hgcAB was effectively absent in ~1500 human microbiomes, suggesting a low risk of endogenous MeHg production. New potential methylation habitats were identified, including invertebrate guts, thawing permafrost, coastal dead zones, soils, sediments, and extreme environments, suggesting multiple routes for MeHg entry into food webs. Several new taxonomic groups potentially capable of Hg-methylation emerged, including lineages having no cultured representatives. We then begin to address long-standing evolutionary questions about Hg-methylation and ancient carbon fixation mechanisms while generating a new global view of Hg-methylation potential.

  18. A synchronized global sweep of the internal genes of modern avian influenza virus.

    PubMed

    Worobey, Michael; Han, Guan-Zhu; Rambaut, Andrew

    2014-04-10

    Zoonotic infectious diseases such as influenza continue to pose a grave threat to human health. However, the factors that mediate the emergence of RNA viruses such as influenza A virus (IAV) are still incompletely understood. Phylogenetic inference is crucial to reconstructing the origins and tracing the flow of IAV within and between hosts. Here we show that explicitly allowing IAV host lineages to have independent rates of molecular evolution is necessary for reliable phylogenetic inference of IAV and that methods that do not do so, including 'relaxed' molecular clock models, can be positively misleading. A phylogenomic analysis using a host-specific local clock model recovers extremely consistent evolutionary histories across all genomic segments and demonstrates that the equine H7N7 lineage is a sister clade to strains from birds--as well as those from humans, swine and the equine H3N8 lineage--sharing an ancestor with them in the mid to late 1800s. Moreover, major western and eastern hemisphere avian influenza lineages inferred for each gene coalesce in the late 1800s. On the basis of these phylogenies and the synchrony of these key nodes, we infer that the internal genes of avian influenza virus (AIV) underwent a global selective sweep beginning in the late 1800s, a process that continued throughout the twentieth century and up to the present. The resulting western hemispheric AIV lineage subsequently contributed most of the genomic segments to the 1918 pandemic virus and, independently, the 1963 equine H3N8 panzootic lineage. This approach provides a clear resolution of evolutionary patterns and processes in IAV, including the flow of viral genes and genomes within and between host lineages.

  19. Global gene expression of a murein (Braun) lipoprotein mutant of Salmonella enterica serovar Typhimurium by microarray analysis.

    PubMed

    Fadl, A A; Galindo, C L; Sha, J; Klimpel, G R; Popov, V L; Chopra, A K

    2006-06-01

    Braun/murein lipoprotein (Lpp) is one of the major outer membrane components of gram-negative enteric bacteria involved in inflammatory responses and septic shock. In previous studies, we reported that two copies of the lipoprotein (lpp) gene (designated as lppA and lppB) existed on the chromosome of Salmonella enterica serovar Typhimurium. Deletion of both lppA and lppB genes rendered Salmonella defective in invasion, motility, induction of cytotoxicity, and production of inflammatory cytokines/chemokines. The lppAB double-knockout (DKO) mutant was attenuated in mice, and animals immunized with this mutant were protected against subsequent challenge with lethal doses of wild-type (wt) S. Typhimurium. To better understand how deletion of the lpp gene might affect Salmonella virulence, we performed global transcriptional profiling of the genes in the wt and the lppAB DKO mutant of S. Typhimurium using microarrays. Our data revealed alterations in the expression of flagellar genes, invasion-associated type III secretion system genes, and transcriptional virulence gene regulators in the lppAB DKO mutant compared to wt S. Typhimurium. These data correlated with the lppAB DKO mutant phenotype and provided possible mechanism(s) of Lpp-associated attenuation in S. Typhimurium. Although these studies were performed in in vitro grown bacteria, our future research will be targeted at global transcriptional profiling of the genes in in vivo grown wt S. Typhimurium and its Lpp mutant.

  20. DGIdb - Mining the druggable genome

    PubMed Central

    Coffman, Adam C.; Weible, James V.; McMichael, Josh F.; Spies, Nicholas C.; Koval, James; Das, Indraniel; Callaway, Matthew B.; Eldred, James M.; Miller, Christopher A.; Subramanian, Janakiraman; Govindan, Ramaswamy; Kumar, Runjun D.; Bose, Ron; Ding, Li; Walker, Jason R.; Larson, David E.; Dooling, David J.; Smith, Scott M.; Ley, Timothy J.; Mardis, Elaine R.; Wilson, Richard K.

    2013-01-01

    The Drug-Gene Interaction database (DGIdb) mines existing resources that generate hypotheses about how mutated genes might be targeted therapeutically or prioritized for drug development. It provides an interface for searching lists of genes against a compendium of drug-gene interactions and potentially druggable genes. DGIdb can be accessed at dgidb.org. PMID:24122041

  1. Global gene expression profiling in infants with acute respiratory syncytial virus broncholitis demonstrates systemic activation of interferon signaling networks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Respiratory syncytial virus (RSV) is a leading cause of pediatric lower respiratory tract infections and has a high impact on pediatric emergency department utilization. Variation in host response may influence the pathogenesis and disease severity. We evaluated global gene expression profiles to be...

  2. Response of the abundance of key soil microbial nitrogen-cycling genes to multi-factorial global changes.

    PubMed

    Zhang, Ximei; Liu, Wei; Schloter, Michael; Zhang, Guangming; Chen, Quansheng; Huang, Jianhui; Li, Linghao; Elser, James J; Han, Xingguo

    2013-01-01

    Multiple co-occurring environmental changes are affecting soil nitrogen cycling processes, which are mainly mediated by microbes. While it is likely that various nitrogen-cycling functional groups will respond differently to such environmental changes, very little is known about their relative responsiveness. Here we conducted four long-term experiments in a steppe ecosystem by removing plant functional groups, mowing, adding nitrogen, adding phosphorus, watering, warming, and manipulating some of their combinations. We quantified the abundance of seven nitrogen-cycling genes, including those for fixation (nifH), mineralization (chiA), nitrification (amoA of ammonia-oxidizing bacteria (AOB) or archaea (AOA)), and denitrification (nirS, nirK and nosZ). First, for each gene, we compared its sensitivities to different environmental changes and found that the abundances of various genes were sensitive to distinct and different factors. Overall, the abundances of nearly all genes were sensitive to nitrogen enrichment. In addition, the abundances of the chiA and nosZ genes were sensitive to plant functional group removal, the AOB-amoA gene abundance to phosphorus enrichment when nitrogen was added simultaneously, and the nirS and nirK gene abundances responded to watering. Second, for each single- or multi-factorial environmental change, we compared the sensitivities of the abundances of different genes and found that different environmental changes primarily affected different gene abundances. Overall, AOB-amoA gene abundance was most responsive, followed by the two denitrifying genes nosZ and nirS, while the other genes were less sensitive. These results provide, for the first time, systematic insights into how the abundance of each type of nitrogen-cycling gene and the equilibrium state of all these nitrogen-cycling gene abundances would shift under each single- or multi-factorial global change.

  3. Inferences about the global scenario of human T-cell lymphotropic virus type 1 infection using data mining of viral sequences

    PubMed Central

    Araujo, Thessika Hialla Almeida; Barreto, Fernanda Khouri; Luiz Carlos, Alcântara; Miranda, Aline Cristina Andrade Mota

    2014-01-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) is mainly associated with two diseases: tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) and adult T-cell leukaemia/lymphoma. This retrovirus infects five-10 million individuals throughout the world. Previously, we developed a database that annotates sequence data from GenBank and the present study aimed to describe the clinical, molecular and epidemiological scenarios of HTLV-1 infection through the stored sequences in this database. A total of 2,545 registered complete and partial sequences of HTLV-1 were collected and 1,967 (77.3%) of those sequences represented unique isolates. Among these isolates, 93% contained geographic origin information and only 39% were related to any clinical status. A total of 1,091 sequences contained information about the geographic origin and viral subtype and 93% of these sequences were identified as subtype “a”. Ethnicity data are very scarce. Regarding clinical status data, 29% of the sequences were generated from TSP/HAM and 67.8% from healthy carrier individuals. Although the data mining enabled some inferences about specific aspects of HTLV-1 infection to be made, due to the relative scarcity of data of available sequences, it was not possible to delineate a global scenario of HTLV-1 infection. PMID:24863974

  4. ChIP-Seq Data Mining: Remarkable Differences in NRSF/REST Target Genes between Human ESC and ESC-Derived Neurons.

    PubMed

    Satoh, Jun-Ichi; Kawana, Natsuki; Yamamoto, Yoji

    2013-01-01

    The neuron-restrictive silencer factor (NRSF) is a zinc finger transcription factor that represses neuronal gene transcription in non-neuronal cells by binding to the consensus repressor element-1 (RE1) located in regulatory regions of target genes. NRSF silences the expression of a wide range of target genes involved in neuron-specific functions. Previous studies showed that aberrant regulation of NRSF plays a key role in the pathological process of human neurodegenerative diseases. However, a comprehensive set of NRSF target genes relevant to human neuronal functions has not yet been characterized. We performed genome-wide data mining from chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) datasets of NRSF binding sites in human embryonic stem cells (ESC) and the corresponding ESC-derived neurons, retrieved from the database of the ENCODE/HAIB project. Using bioinformatics tools such as Avadis NGS and MACS, we identified 2,172 NRSF target genes in ESC and 308 genes in ESC-derived neurons based on stringent criteria. Only 40 NRSF target genes overlapped between both data sets. According to motif analysis, binding regions showed an enrichment of the consensus RE1 sites in ESC, whereas they were mainly located in poorly defined non-RE1 sites in ESC-derived neurons. Molecular pathways of NRSF target genes were linked with various neuronal functions in ESC, such as neuroactive ligand-receptor interaction, CREB signaling, and axonal guidance signaling, while they were not directed to neuron-specific functions in ESC-derived neurons. Remarkable differences in ChIP-Seq-based NRSF target genes and pathways between ESC and ESC-derived neurons suggested that NRSF-mediated silencing of target genes is highly effective in human ESC but not in ESC-derived neurons. PMID:24324330

  5. A global immune deficit in Alzheimer's disease and mild cognitive impairment disclosed by a novel data mining process.

    PubMed

    Gironi, Maira; Borgiani, Bruno; Farina, Elisabetta; Mariani, Enrica; Cursano, Cristina; Alberoni, Margherita; Nemni, Raffaello; Comi, Giancarlo; Buscema, Massimo; Furlan, Roberto; Grossi, Enzo

    2015-01-01

    Alzheimer's disease (AD) is the most common form of dementia, while mild cognitive impairment (MCI) causes a slight but measurable decline in cognitive abilities. A person with MCI has an increased risk of developing AD or another dementia. Thus, it is of medical interest to develop predictive tools to assess this risk. A growing awareness exists that pro-oxidative state and neuro-inflammation are both involved in AD. However, the extent of this relationship is still a matter of debate. Due to the expected non-linear correlations between oxidative and inflammatory markers, traditional statistics is unsuitable to dissect their relationship with the disease. Artificial neural networks (ANNs) are computational models inspired by central nervous system networks, capable of machine learning and pattern recognition. The aim of this work was to disclose the relationship between immunological and oxidative stress markers in AD and MCI by the application of ANNs. Through a machine learning approach, we were able to construct an algorithm to classify MCI and AD with high accuracy. Such an instrument, requiring a small amount of immunological and oxidative-stress parameters, would be useful in the clinical practice. Moreover, applying an innovative non-linear mathematical technique, a global immune deficit was shown to be associated with cognitive impairment. Surprisingly, both adaptive and innate immunity were peripherally defective in AD and MCI patients. From this study, new pathogenetic aspects of these diseases could emerge.

  6. Global Mapping of Gene/Protein Interactions in PubMed Abstracts: A Framework and an Experiment with P53 Interactions

    PubMed Central

    Li, Xin; Chen, Hsinchun; Huang, Zan; Su, Hua; Martinez, Jesse D.

    2007-01-01

    Gene/protein interactions provide critical information for a thorough understanding of cellular processes. Recently, considerable interest and effort has been focused on the construction and analysis of genome-wide gene networks. The large body of biomedical literature is an important source of gene/protein interaction information. Recent advances in text mining tools have made it possible to automatically extract such documented interactions from free-text literature. In this paper, we propose a comprehensive framework for constructing and analyzing large-scale gene functional networks based on the gene/protein interactions extracted from biomedical literature repositories using text mining tools. Our proposed framework consists of analyses of the network topology, network topology-gene function relationship, and temporal network evolution to distill valuable information embedded in the gene functional interactions in literature. We demonstrate the application of the proposed framework using a testbed of P53-related PubMed abstracts, which shows that literature-based P53 networks exhibit small-world and scale-free properties. We also found that high degree genes in the literature-based networks have a high probability of appearing in the manually curated database and genes in the same pathway tend to form local clusters in our literature-based networks. Temporal analysis showed that genes interacting with many other genes tend to be involved in a large number of newly discovered interactions. PMID:17317333

  7. Global Analysis of Posttranscriptional Gene Expression in Response to Sodium Arsenite

    PubMed Central

    Qiu, Lian-Qun; Abey, Sarah; Harris, Shawn; Shah, Ruchir; Gerrish, Kevin E.

    2014-01-01

    Background: Inorganic arsenic species are potent environmental toxins and causes of numerous health problems. Most studies have assumed that arsenic-induced changes in mRNA levels result from effects on gene transcription. Objectives: We evaluated the prevalence of changes in mRNA stability in response to sodium arsenite in human fibroblasts. Methods: We used microarray analyses to determine changes in steady-state mRNA levels and mRNA decay rates following 24-hr exposure to noncytotoxic concentrations of sodium arsenite, and we confirmed some of these changes using real-time reverse-transcription polymerase chain reaction (RT-PCR). Results: In arsenite-exposed cells, 186 probe set–identified transcripts were significantly increased and 167 were significantly decreased. When decay rates were analyzed after actinomycin D treatment, only 4,992 (9.1%) of probe set–identified transcripts decayed by > 25% after 4 hr. Of these, 70 were among the 353 whose steady-state levels were altered by arsenite, and of these, only 4 exhibited significantly different decay rates between arsenite and control treatment. Real-time RT-PCR confirmed a major, significant arsenite-induced stabilization of the mRNA encoding δ aminolevulinate synthase 1 (ALAS1), the rate-limiting enzyme in heme biosynthesis. This change presumably accounted for at least part of the 2.7-fold increase in steady-state ALAS1 mRNA levels seen after arsenite treatment. This could reflect decreases in cellular heme caused by the massive induction by arsenite of heme oxygenase mRNA (HMOX1; 68-fold increase), the rate-limiting enzyme in heme catabolism. Conclusions: We conclude that arsenite modification of mRNA stability is relatively uncommon, but in some instances can result in significant changes in gene expression. Citation: Qiu LQ, Abey S, Harris S, Shah R, Gerrish KE, Blackshear PJ. 2015. Global analysis of posttranscriptional gene expression in response to sodium arsenite. Environ Health Perspect 123:324

  8. Global regulation of gene expression and cell differentiation in Caulobacter crescentus in response to nutrient availability.

    PubMed

    England, Jennifer C; Perchuk, Barrett S; Laub, Michael T; Gober, James W

    2010-02-01

    In a developmental strategy designed to efficiently exploit and colonize sparse oligotrophic environments, Caulobacter crescentus cells divide asymmetrically, yielding a motile swarmer cell and a sessile stalked cell. After a relatively fixed time period under typical culture conditions, the swarmer cell differentiates into a replicative stalked cell. Since differentiation into the stalked cell type is irreversible, it is likely that environmental factors such as the availability of essential nutrients would influence the timing of the decision to abandon motility and adopt a sessile lifestyle. We measured two different parameters in nutrient-limited chemostat cultures, biomass concentration and the ratio of nonstalked to stalked cells, over a range of flow rates and found that nitrogen limitation significantly extended the swarmer cell life span. The transcriptional profiling experiments described here generate the first comprehensive picture of the global regulatory strategies used by an oligotroph when confronted with an environment where key macronutrients are sparse. The pattern of regulated gene expression in nitrogen- and carbon-limited cells shares some features in common with most copiotrophic organisms, but critical differences suggest that Caulobacter, and perhaps other oligotrophs, have evolved regulatory strategies to deal distinctly with their natural environments. We hypothesize that nitrogen limitation extends the swarmer cell lifetime by delaying the onset of a sequence of differentiation events, which when initiated by the correct combination of external environmental cues, sets the swarmer cell on a path to differentiate into a stalked cell within a fixed time period.

  9. Swimming in the deep end of the gene pool: global population structure of an oceanic giant.

    PubMed

    Bradshaw, Corey J A

    2007-12-01

    Despite the impression held by some that few biological mysteries remain, even evocative species such as humpback whales (Megaptera novaeangliae), white sharks (Carcharodon carcharias) and green turtles (Chelonia mydas) have poorly documented movement patterns, reproductive strategies and population dynamics despite years of dedicated research. This is largely due to the difficulty of observing wide-ranging marine species over the majority of their life cycle. The advent of powerful tracking devices has certainly improved our understanding, but it is usually only with molecular tools that the nature of population structure becomes apparent. In this issue of Molecular Ecology, Castro and colleagues have provided the first global-scale assessment of population structure for the largest fish--whale sharks (Rhincodon typus). Whale sharks can reach lengths > 12 m and are a popular tourist attraction at places where they aggregate, yet for most of their life cycle, we know little indeed of where they go and how they interact with other populations. Previous tracking studies imply a high dispersal capacity, but only now have Castro and colleagues demonstrated high gene flow and haplotype diversity among the major ocean basins where they are found.

  10. Global Gene Expression and Focused Knockout Analysis Reveals Genes Associated with Fungal Fruiting Body Development in Neurospora crassa

    PubMed Central

    Wang, Zheng; Lopez-Giraldez, Francesc; Lehr, Nina; Farré, Marta; Common, Ralph; Trail, Frances

    2014-01-01

    Fungi can serve as highly tractable models for understanding genetic basis of sexual development in multicellular organisms. Applying a reverse-genetic approach to advance such a model, we used random and multitargeted primers to assay gene expression across perithecial development in Neurospora crassa. We found that functionally unclassified proteins accounted for most upregulated genes, whereas downregulated genes were enriched for diverse functions. Moreover, genes associated with developmental traits exhibited stage-specific peaks of expression. Expression increased significantly across sexual development for mating type gene mat a-1 and for mat A-1 specific pheromone precursor ccg-4. In addition, expression of a gene encoding a protein similar to zinc finger, stc1, was highly upregulated early in perithecial development, and a strain with a knockout of this gene exhibited arrest at the same developmental stage. A similar expression pattern was observed for genes in RNA silencing and signaling pathways, and strains with knockouts of these genes were also arrested at stages of perithecial development that paralleled their peak in expression. The observed stage specificity allowed us to correlate expression upregulation and developmental progression and to identify regulators of sexual development. Bayesian networks inferred from our expression data revealed previously known and new putative interactions between RNA silencing genes and pathways. Overall, our analysis provides a fine-scale transcriptomic landscape and novel inferences regarding the control of the multistage development process of sexual crossing and fruiting body development in N. crassa. PMID:24243796

  11. Global analysis of gene expression changes during retinoic acid-induced growth arrest and differentiation of melanoma: comparison to differentially expressed genes in melanocytes vs melanoma

    PubMed Central

    Estler, Mary; Boskovic, Goran; Denvir, James; Miles, Sarah; Primerano, Donald A; Niles, Richard M

    2008-01-01

    Background The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood. Results In an analysis of sequential global gene expression changes during a 4–48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and B16 melanoma cells. Using the same statistical test, we found 1495 genes whose expression was significantly higher in melan-a than in B16 cells and 2054 genes whose expression was significantly lower in melan-a than in B16 cells. By intersecting these two gene sets, we discovered a common set of 233 genes whose RNA levels were significantly different between B16 and melan-a cells and whose expression was altered by RA treatment. Within this set, RA treatment altered the expression of 203 (87%) genes toward the melan-a expression level. In addition, hierarchical clustering showed that after 48 h of RA treatment expression of the 203 genes was more closely related to the melan-a gene set than any other RA treatment time point. Functional analysis of the 203 gene set indicated that RA decreased expression of mRNAs that encode proteins involved in cell division/cell cycle, DNA replication, recombination and repair, and transcription regulation. Conversely, it stimulated genes involved in cell-cell signaling, cell adhesion and cell differentiation/embryonic development. Pathway analysis of the 203 gene set revealed four major hubs of connectivity: CDC2, CHEK1, CDC45L and MCM6. Conclusion Our analysis of common genes in the 48 h RA-treatment of B16 melanoma cells and untreated B16 vs. melan-a data set show

  12. Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes

    DOE PAGES

    Alam, Tanvir; Medvedeva, Yulia A.; Jia, Hui; Brown, James B.; Lipovich, Leonard; Bajic, Vladimir B.; Mantovani, Roberto

    2014-10-02

    Transcriptional regulation of protein-coding genes is increasingly well-understood on a global scale, yet no comparable information exists for long non-coding RNA (lncRNA) genes, which were recently recognized to be as numerous as protein-coding genes in mammalian genomes. We performed a genome-wide comparative analysis of the promoters of human lncRNA and protein-coding genes, finding global differences in specific genetic and epigenetic features relevant to transcriptional regulation. These two groups of genes are hence subject to separate transcriptional regulatory programs, including distinct transcription factor (TF) proteins that significantly favor lncRNA, rather than coding-gene, promoters. We report a specific signature of promoter-proximal transcriptionalmore » regulation of lncRNA genes, including several distinct transcription factor binding sites (TFBS). Experimental DNase I hypersensitive site profiles are consistent with active configurations of these lncRNA TFBS sets in diverse human cell types. TFBS ChIP-seq datasets confirm the binding events that we predicted using computational approaches for a subset of factors. For several TFs known to be directly regulated by lncRNAs, we find that their putative TFBSs are enriched at lncRNA promoters, suggesting that the TFs and the lncRNAs may participate in a bidirectional feedback loop regulatory network. Accordingly, cells may be able to modulate lncRNA expression levels independently of mRNA levels via distinct regulatory pathways. Our results also raise the possibility that, given the historical reliance on protein-coding gene catalogs to define the chromatin states of active promoters, a revision of these chromatin signature profiles to incorporate expressed lncRNA genes is warranted in the future.« less

  13. Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes

    SciTech Connect

    Alam, Tanvir; Medvedeva, Yulia A.; Jia, Hui; Brown, James B.; Lipovich, Leonard; Bajic, Vladimir B.; Mantovani, Roberto

    2014-10-02

    Transcriptional regulation of protein-coding genes is increasingly well-understood on a global scale, yet no comparable information exists for long non-coding RNA (lncRNA) genes, which were recently recognized to be as numerous as protein-coding genes in mammalian genomes. We performed a genome-wide comparative analysis of the promoters of human lncRNA and protein-coding genes, finding global differences in specific genetic and epigenetic features relevant to transcriptional regulation. These two groups of genes are hence subject to separate transcriptional regulatory programs, including distinct transcription factor (TF) proteins that significantly favor lncRNA, rather than coding-gene, promoters. We report a specific signature of promoter-proximal transcriptional regulation of lncRNA genes, including several distinct transcription factor binding sites (TFBS). Experimental DNase I hypersensitive site profiles are consistent with active configurations of these lncRNA TFBS sets in diverse human cell types. TFBS ChIP-seq datasets confirm the binding events that we predicted using computational approaches for a subset of factors. For several TFs known to be directly regulated by lncRNAs, we find that their putative TFBSs are enriched at lncRNA promoters, suggesting that the TFs and the lncRNAs may participate in a bidirectional feedback loop regulatory network. Accordingly, cells may be able to modulate lncRNA expression levels independently of mRNA levels via distinct regulatory pathways. Our results also raise the possibility that, given the historical reliance on protein-coding gene catalogs to define the chromatin states of active promoters, a revision of these chromatin signature profiles to incorporate expressed lncRNA genes is warranted in the future.

  14. Longwall mining

    SciTech Connect

    1995-03-14

    As part of EIA`s program to provide information on coal, this report, Longwall-Mining, describes longwall mining and compares it with other underground mining methods. Using data from EIA and private sector surveys, the report describes major changes in the geologic, technological, and operating characteristics of longwall mining over the past decade. Most important, the report shows how these changes led to dramatic improvements in longwall mining productivity. For readers interested in the history of longwall mining and greater detail on recent developments affecting longwall mining, the report includes a bibliography.

  15. Brucella melitensis global gene expression study provides novel information on growth phase-specific gene regulation with potential insights for understanding Brucella:host initial interactions

    PubMed Central

    2009-01-01

    Background Brucella spp. are the etiological agents of brucellosis, a zoonotic infectious disease that causes abortion in animals and chronic debilitating illness in humans. Natural Brucella infections occur primarily through an incompletely defined mechanism of adhesion to and penetration of mucosal epithelium. In this study, we characterized changes in genome-wide transcript abundance of the most and the least invasive growth phases of B. melitensis cultures to HeLa cells, as a preliminary approach for identifying candidate pathogen genes involved in invasion of epithelial cells. Results B. melitensis at the late logarithmic phase of growth are more invasive to HeLa cells than mid-logarithmic or stationary growth phases. Microarray analysis of B. melitensis gene expression identified 414 up- and 40 down-regulated genes in late-log growth phase (the most invasive culture) compared to the stationary growth phase (the least invasive culture). As expected, the majority of up-regulated genes in late-log phase cultures were those associated with growth, including DNA replication, transcription, translation, intermediate metabolism, energy production and conversion, membrane transport, and biogenesis of the cell envelope and outer membrane; while the down-regulated genes were distributed among several functional categories. Conclusion This Brucella global expression profile study provides novel information on growth phase-specific gene expression. Further characterization of some genes found differentially expressed in the most invasive culture will likely bring new insights into the initial molecular interactions between Brucella and its host. PMID:19419566

  16. Highly expressed amino acid biosynthesis genes revealed by global gene expression analysis of Salmonella enterica serovar Enteritidis during growth in whole egg are not essential for this growth.

    PubMed

    Jakočiūnė, Džiuginta; Herrero-Fresno, Ana; Jelsbak, Lotte; Olsen, John Elmerdahl

    2016-05-01

    Salmonella enterica serovar Enteritidis (S. Enteritidis) is the most common cause of egg borne salmonellosis in many parts of the world. This study analyzed gene expression of this bacterium during growth in whole egg, and whether highly expressed genes were essential for the growth. High quality RNA was extracted from S. Enteritidis using a modified RNA-extraction protocol. Global gene expression during growth in whole egg was compared to growth in LB-medium using DNA array method. Twenty-six genes were significantly upregulated during growth in egg; these belonged to amino acid biosynthesis, di/oligopeptide transport system, biotin synthesis, ferrous iron transport system, and type III secretion system. Significant downregulation of 15 genes related to formate hydrogenlyase (FHL) and trehalose metabolism was observed. The results suggested that S. Enteritidis is starved for amino-acids, biotin and iron when growing in egg. However, site specific mutation of amino acid biosynthesis genes asnA (17.3 fold upregulated), asnB (18.6 fold upregulated), asnA/asnB and, serA (12.0 fold upregulated) and gdhA (3.7 fold upregulated), did not result in growth attenuation, suggesting that biosynthesis using the enzymes encoded from these genes may represent the first choice for S. Enteritidis when growing in egg, but when absent, the bacterium could use alternative ways to obtain the amino acids. PMID:26945769

  17. Highly expressed amino acid biosynthesis genes revealed by global gene expression analysis of Salmonella enterica serovar Enteritidis during growth in whole egg are not essential for this growth.

    PubMed

    Jakočiūnė, Džiuginta; Herrero-Fresno, Ana; Jelsbak, Lotte; Olsen, John Elmerdahl

    2016-05-01

    Salmonella enterica serovar Enteritidis (S. Enteritidis) is the most common cause of egg borne salmonellosis in many parts of the world. This study analyzed gene expression of this bacterium during growth in whole egg, and whether highly expressed genes were essential for the growth. High quality RNA was extracted from S. Enteritidis using a modified RNA-extraction protocol. Global gene expression during growth in whole egg was compared to growth in LB-medium using DNA array method. Twenty-six genes were significantly upregulated during growth in egg; these belonged to amino acid biosynthesis, di/oligopeptide transport system, biotin synthesis, ferrous iron transport system, and type III secretion system. Significant downregulation of 15 genes related to formate hydrogenlyase (FHL) and trehalose metabolism was observed. The results suggested that S. Enteritidis is starved for amino-acids, biotin and iron when growing in egg. However, site specific mutation of amino acid biosynthesis genes asnA (17.3 fold upregulated), asnB (18.6 fold upregulated), asnA/asnB and, serA (12.0 fold upregulated) and gdhA (3.7 fold upregulated), did not result in growth attenuation, suggesting that biosynthesis using the enzymes encoded from these genes may represent the first choice for S. Enteritidis when growing in egg, but when absent, the bacterium could use alternative ways to obtain the amino acids.

  18. Global Expression Profiling of Transcription Factor Genes Provides New Insights into Pathogenicity and Stress Responses in the Rice Blast Fungus

    PubMed Central

    Park, Sook-Young; Choi, Jaeyoung; Lim, Se-Eun; Lee, Gir-Won; Park, Jongsun; Kim, Yang; Kong, Sunghyung; Kim, Se Ryun; Rho, Hee-Sool; Jeon, Junhyun; Chi, Myung-Hwan; Kim, Soonok; Khang, Chang Hyun; Kang, Seogchan; Lee, Yong-Hwan

    2013-01-01

    Because most efforts to understand the molecular mechanisms underpinning fungal pathogenicity have focused on studying the function and role of individual genes, relatively little is known about how transcriptional machineries globally regulate and coordinate the expression of a large group of genes involved in pathogenesis. Using quantitative real-time PCR, we analyzed the expression patterns of 206 transcription factor (TF) genes in the rice blast fungus Magnaporthe oryzae under 32 conditions, including multiple infection-related developmental stages and various abiotic stresses. The resulting data, which are publicly available via an online platform, provided new insights into how these TFs are regulated and potentially work together to control cellular responses to a diverse array of stimuli. High degrees of differential TF expression were observed under the conditions tested. More than 50% of the 206 TF genes were up-regulated during conidiation and/or in conidia. Mutations in ten conidiation-specific TF genes caused defects in conidiation. Expression patterns in planta were similar to those under oxidative stress conditions. Mutants of in planta inducible genes not only exhibited sensitive to oxidative stress but also failed to infect rice. These experimental validations clearly demonstrated the value of TF expression patterns in predicting the function of individual TF genes. The regulatory network of TF genes revealed by this study provides a solid foundation for elucidating how M. oryzae regulates its pathogenesis, development, and stress responses. PMID:23762023

  19. Data mining reveals a network of early-response genes as a consensus signature of drug-induced in vitro and in vivo toxicity.

    PubMed

    Zhang, J D; Berntenis, N; Roth, A; Ebeling, M

    2014-06-01

    Gene signatures of drug-induced toxicity are of broad interest, but they are often identified from small-scale, single-time point experiments, and are therefore of limited applicability. To address this issue, we performed multivariate analysis of gene expression, cell-based assays, and histopathological data in the TG-GATEs (Toxicogenomics Project-Genomics Assisted Toxicity Evaluation system) database. Data mining highlights four genes-EGR1, ATF3, GDF15 and FGF21-that are induced 2 h after drug administration in human and rat primary hepatocytes poised to eventually undergo cytotoxicity-induced cell death. Modelling and simulation reveals that these early stress-response genes form a functional network with evolutionarily conserved structure and intrinsic dynamics. This is underlined by the fact that early induction of this network in vivo predicts drug-induced liver and kidney pathology with high accuracy. Our findings demonstrate the value of early gene-expression signatures in predicting and understanding compound-induced toxicity. The identified network can empower first-line tests that reduce animal use and costs of safety evaluation.

  20. Global Analysis of Gene Expression Profiles in Physic Nut (Jatropha curcas L.) Seedlings Exposed to Salt Stress

    PubMed Central

    Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

    2014-01-01

    Background Salt stress interferes with plant growth and production. Plants have evolved a series of molecular and morphological adaptations to cope with this abiotic stress, and overexpression of salt response genes reportedly enhances the productivity of various crops. However, little is known about the salt responsive genes in the energy plant physic nut (Jatropha curcas L.). Thus, excavate salt responsive genes in this plant are informative in uncovering the molecular mechanisms for the salt response in physic nut. Methodology/Principal Findings We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of physic nut plants (roots and leaves) 2 hours, 2 days and 7 days after the onset of salt stress. A total of 1,504 and 1,115 genes were significantly up and down-regulated in roots and leaves, respectively, under salt stress condition. Gene ontology (GO) analysis of physiological process revealed that, in the physic nut, many “biological processes” were affected by salt stress, particular those categories belong to “metabolic process”, such as “primary metabolism process”, “cellular metabolism process” and “macromolecule metabolism process”. The gene expression profiles indicated that the associated genes were responsible for ABA and ethylene signaling, osmotic regulation, the reactive oxygen species scavenging system and the cell structure in physic nut. Conclusions/Significance The major regulated genes detected in this transcriptomic data were related to trehalose synthesis and cell wall structure modification in roots, while related to raffinose synthesis and reactive oxygen scavenger in leaves. The current study shows a comprehensive gene expression profile of physic nut under salt stress. The differential expression genes detected in this study allows the underling the salt responsive mechanism in physic nut with the aim of improving its salt resistance in the future. PMID:24837971

  1. Prostaglandin E₂ increases fibroblast gene-specific and global DNA methylation via increased DNA methyltransferase expression.

    PubMed

    Huang, Steven K; Scruggs, Anne M; Donaghy, Jake; McEachin, Richard C; Fisher, Aaron S; Richardson, Bruce C; Peters-Golden, Marc

    2012-09-01

    Although alterations in DNA methylation patterns have been associated with specific diseases and environmental exposures, the mediators and signaling pathways that direct these changes remain understudied. The bioactive lipid mediator prostaglandin E(2) (PGE(2)) has been shown to exert a myriad of effects on cell survival, proliferation, and differentiation. Here, we report that PGE(2) also signals to increase global DNA methylation and DNA methylation machinery in fibroblasts. HumanMethylation27 BeadChip array analysis of primary fetal (IMR-90) and adult lung fibroblasts identified multiple genes that were hypermethylated in response to PGE(2). PGE(2), compared with nontreated controls, increased expression and activity (EC(50)∼10(7) M) of one specific isoform of DNA methyltransferase, DNMT3a. Silencing of DNMT3a negated the ability of PGE(2) to increase DNMT activity. The increase in DNMT3a expression was mediated by PGE(2) signaling via its E prostanoid 2 receptor and the second messenger cAMP. PGE(2), compared with the untreated control, increased the expression and activity of Sp1 and Sp3 (EC(50)∼3×10(7) M), transcription factors known to increase DNMT3a expression, and inhibition of these transcription factors abrogated the PGE(2) increase of DNMT3a expression. These findings were specific to fibroblasts, as PGE(2) decreased DNMT1 and DNMT3a expression in RAW macrophages. Taken together, these findings establish that DNA methylation is regulated by a ubiquitous bioactive endogenous mediator. Given that PGE(2) biosynthesis is modulated by environmental toxins, various disease states, and commonly used pharmacological agents, these findings uncover a novel mechanism by which alterations in DNA methylation patterns may arise in association with disease and certain environmental exposures.

  2. "Every Gene Is Everywhere but the Environment Selects": Global Geolocalization of Gene Sharing in Environmental Samples through Network Analysis.

    PubMed

    Fondi, Marco; Karkman, Antti; Tamminen, Manu V; Bosi, Emanuele; Virta, Marko; Fani, Renato; Alm, Eric; McInerney, James O

    2016-01-01

    The spatial distribution of microbes on our planet is famously formulated in the Baas Becking hypothesis as "everything is everywhere but the environment selects." While this hypothesis does not strictly rule out patterns caused by geographical effects on ecology and historical founder effects, it does propose that the remarkable dispersal potential of microbes leads to distributions generally shaped by environmental factors rather than geographical distance. By constructing sequence similarity networks from uncultured environmental samples, we show that microbial gene pool distributions are not influenced nearly as much by geography as ecology, thus extending the Bass Becking hypothesis from whole organisms to microbial genes. We find that gene pools are shaped by their broad ecological niche (such as sea water, fresh water, host, and airborne). We find that freshwater habitats act as a gene exchange bridge between otherwise disconnected habitats. Finally, certain antibiotic resistance genes deviate from the general trend of habitat specificity by exhibiting a high degree of cross-habitat mobility. The strong cross-habitat mobility of antibiotic resistance genes is a cause for concern and provides a paradigmatic example of the rate by which genes colonize new habitats when new selective forces emerge. PMID:27190206

  3. "Every Gene Is Everywhere but the Environment Selects": Global Geolocalization of Gene Sharing in Environmental Samples through Network Analysis.

    PubMed

    Fondi, Marco; Karkman, Antti; Tamminen, Manu V; Bosi, Emanuele; Virta, Marko; Fani, Renato; Alm, Eric; McInerney, James O

    2016-05-13

    The spatial distribution of microbes on our planet is famously formulated in the Baas Becking hypothesis as "everything is everywhere but the environment selects." While this hypothesis does not strictly rule out patterns caused by geographical effects on ecology and historical founder effects, it does propose that the remarkable dispersal potential of microbes leads to distributions generally shaped by environmental factors rather than geographical distance. By constructing sequence similarity networks from uncultured environmental samples, we show that microbial gene pool distributions are not influenced nearly as much by geography as ecology, thus extending the Bass Becking hypothesis from whole organisms to microbial genes. We find that gene pools are shaped by their broad ecological niche (such as sea water, fresh water, host, and airborne). We find that freshwater habitats act as a gene exchange bridge between otherwise disconnected habitats. Finally, certain antibiotic resistance genes deviate from the general trend of habitat specificity by exhibiting a high degree of cross-habitat mobility. The strong cross-habitat mobility of antibiotic resistance genes is a cause for concern and provides a paradigmatic example of the rate by which genes colonize new habitats when new selective forces emerge.

  4. Analysis of global gene expression profiles to identify differentially expressed genes critical for embryo development in Brassica rapa.

    PubMed

    Zhang, Yu; Peng, Lifang; Wu, Ya; Shen, Yanyue; Wu, Xiaoming; Wang, Jianbo

    2014-11-01

    Embryo development represents a crucial developmental period in the life cycle of flowering plants. To gain insights into the genetic programs that control embryo development in Brassica rapa L., RNA sequencing technology was used to perform transcriptome profiling analysis of B. rapa developing embryos. The results generated 42,906,229 sequence reads aligned with 32,941 genes. In total, 27,760, 28,871, 28,384, and 25,653 genes were identified from embryos at globular, heart, early cotyledon, and mature developmental stages, respectively, and analysis between stages revealed a subset of stage-specific genes. We next investigated 9,884 differentially expressed genes with more than fivefold changes in expression and false discovery rate ≤ 0.001 from three adjacent-stage comparisons; 1,514, 3,831, and 6,633 genes were detected between globular and heart stage embryo libraries, heart stage and early cotyledon stage, and early cotyledon and mature stage, respectively. Large numbers of genes related to cellular process, metabolism process, response to stimulus, and biological process were expressed during the early and middle stages of embryo development. Fatty acid biosynthesis, biosynthesis of secondary metabolites, and photosynthesis-related genes were expressed predominantly in embryos at the middle stage. Genes for lipid metabolism and storage proteins were highly expressed in the middle and late stages of embryo development. We also identified 911 transcription factor genes that show differential expression across embryo developmental stages. These results increase our understanding of the complex molecular and cellular events during embryo development in B. rapa and provide a foundation for future studies on other oilseed crops.

  5. Global indiscriminate methylation in cell-specific gene promoters following reprogramming into human induced pluripotent stem cells.

    PubMed

    Nissenbaum, Jonathan; Bar-Nur, Ori; Ben-David, Eyal; Benvenisty, Nissim

    2013-01-01

    Molecular reprogramming of somatic cells into human induced pluripotent stem cells (iPSCs) is accompanied by extensive changes in gene expression patterns and epigenetic marks. To better understand the link between gene expression and DNA methylation, we have profiled human somatic cells from different embryonic cell types (endoderm, mesoderm, and parthenogenetic germ cells) and the iPSCs generated from them. We show that reprogramming is accompanied by extensive DNA methylation in CpG-poor promoters, sparing CpG-rich promoters. Intriguingly, methylation in CpG-poor promoters occurred not only in downregulated genes, but also in genes that are not expressed in the parental somatic cells or their respective iPSCs. These genes are predominantly tissue-specific genes of other cell types from different lineages. Our results suggest a role of DNA methylation in the silencing of the somatic cell identity by global nonspecific methylation of tissue-specific genes from all lineages, regardless of their expression in the parental somatic cells. PMID:24371806

  6. Global regulation of reactive oxygen species scavenging genes in alfalfa root and shoot under gradual drought stress and recovery.

    PubMed

    Kang, Yun; Udvardi, Michael

    2012-05-01

    Reactive oxygen species (ROS) production and scavenging in plants under drought stress have been studied intensively in recent years. Here we report a global analysis of gene expression for the major ROS generating and scavenging proteins in alfalfa root and shoot under gradual drought stress followed by one-day recovery. Data from two alfalfa varieties, one drought tolerant and one drought sensitive, were compared and no qualitative differences in ROS gene regulation between the two were found. Conserved, tissue-specific patterns of gene expression in response to drought were observed for several ROS-scavenging gene families, including ascorbate peroxidase, monodehydroascorbate reductase, and peroxiredoxin. In addition, differential gene expression within families was observed. Genes for the ROS-generating enzyme, NADPH oxidase were generally induced under drought, while those for glycolate oxidase were repressed. Among the ROS-scavenging protein genes, Ferritin, Cu/Zn superoxide dismutase (SOD), and the majority of the glutathione peroxidase family members were induced under drought in both roots and shoots of both alfalfa varieties. In contrast, Fe-SOD, CC-type glutaredoxins, and thoiredoxins were downregulated.

  7. Global indiscriminate methylation in cell-specific gene promoters following reprogramming into human induced pluripotent stem cells.

    PubMed

    Nissenbaum, Jonathan; Bar-Nur, Ori; Ben-David, Eyal; Benvenisty, Nissim

    2013-01-01

    Molecular reprogramming of somatic cells into human induced pluripotent stem cells (iPSCs) is accompanied by extensive changes in gene expression patterns and epigenetic marks. To better understand the link between gene expression and DNA methylation, we have profiled human somatic cells from different embryonic cell types (endoderm, mesoderm, and parthenogenetic germ cells) and the iPSCs generated from them. We show that reprogramming is accompanied by extensive DNA methylation in CpG-poor promoters, sparing CpG-rich promoters. Intriguingly, methylation in CpG-poor promoters occurred not only in downregulated genes, but also in genes that are not expressed in the parental somatic cells or their respective iPSCs. These genes are predominantly tissue-specific genes of other cell types from different lineages. Our results suggest a role of DNA methylation in the silencing of the somatic cell identity by global nonspecific methylation of tissue-specific genes from all lineages, regardless of their expression in the parental somatic cells.

  8. Global Indiscriminate Methylation in Cell-Specific Gene Promoters following Reprogramming into Human Induced Pluripotent Stem Cells

    PubMed Central

    Nissenbaum, Jonathan; Bar-Nur, Ori; Ben-David, Eyal; Benvenisty, Nissim

    2013-01-01

    Summary Molecular reprogramming of somatic cells into human induced pluripotent stem cells (iPSCs) is accompanied by extensive changes in gene expression patterns and epigenetic marks. To better understand the link between gene expression and DNA methylation, we have profiled human somatic cells from different embryonic cell types (endoderm, mesoderm, and parthenogenetic germ cells) and the iPSCs generated from them. We show that reprogramming is accompanied by extensive DNA methylation in CpG-poor promoters, sparing CpG-rich promoters. Intriguingly, methylation in CpG-poor promoters occurred not only in downregulated genes, but also in genes that are not expressed in the parental somatic cells or their respective iPSCs. These genes are predominantly tissue-specific genes of other cell types from different lineages. Our results suggest a role of DNA methylation in the silencing of the somatic cell identity by global nonspecific methylation of tissue-specific genes from all lineages, regardless of their expression in the parental somatic cells. PMID:24371806

  9. Population-specificity of heat stress gene induction in northern and southern eelgrass Zostera marina populations under simulated global warming.

    PubMed

    Bergmann, Nina; Winters, Gidon; Rauch, Gisep; Eizaguirre, Christophe; Gu, Jenny; Nelle, Peter; Fricke, Birgit; Reusch, Thorsten B H

    2010-07-01

    Summer heat waves have already resulted in mortality of coastal communities, including ecologically important seagrass meadows. Gene expression studies from controlled experiments can provide important insight as to how species/genotypes react to extreme events that will increase under global warming. In a common stress garden, we exposed three populations of eelgrass, Zostera marina, to extreme sea surface temperatures, simulating the 2003-European heat wave. Populations came from locations widely differing in their thermal regime, two northern European locations [Ebeltoft (Kattegat), Doverodde (Limfjord, Baltic Sea)], and one southern population from Gabicce Mare (Adriatic Sea), allowing to test for population specificity in the response to a realistic heat stress event. Eelgrass survival and growth as well as the expression of 12 stress associated candidate genes were assessed during and after the heat wave. Contrary to expectations, all populations suffered equally from 3 weeks of heat stress in terms of shoot loss. In contrast, populations markedly differed in multivariate measures of gene expression. While the gene expression profiles converged to pre-stress values directly after the heat wave, stress correlated genes were upregulated again 4 weeks later, in line with the observed delay in shoot loss. Target genes had to be selected based on functional knowledge in terrestrial plants, nevertheless, 10/12 genes were induced relative to the control treatment at least once during the heat wave in the fully marine plant Z. marina. This study underlines the importance of realistic stress and recovery scenarios in studying the impact of predicted climate change.

  10. Binding Motifs in Bacterial Gene Promoters Modulate Transcriptional Effects of Global Regulators CRP and ArcA

    PubMed Central

    Leuze, Michael R.; Karpinets, Tatiana V.; Syed, Mustafa H.; Beliaev, Alexander S.; Uberbacher, Edward C.

    2012-01-01

    Bacterial gene regulation involves transcription factors (TF) that bind to DNA recognition sequences in operon promoters. These recognition sequences, many of which are palindromic, are known as regulatory elements or transcription factor binding sites (TFBS). Some TFs are global regulators that can modulate the expression of hundreds of genes. In this study we examine global regulator half-sites, where a half-site, which we shall call a binding motif (BM), is one half of a palindromic TFBS. We explore the hypothesis that the number of BMs plays an important role in transcriptional regulation, examining empirical data from transcriptional profiling of the CRP and ArcA regulons. We compare the power of BM counts and of full TFBS characteristics to predict induced transcriptional activity. We find that CRP BM counts have a nonlinear effect on CRP-dependent transcriptional activity and predict this activity better than full TFBS quality or location. PMID:22701314

  11. Binding motifs in bacterial gene promoters modulate transcriptional effects of global regulators CRP and ArcA

    SciTech Connect

    Leuze, Mike; Karpinets, Tatiana V.; Syed, Mustafa H.; Beliaev, Alex S.; Uberbacher, Edward

    2012-05-30

    Bacterial gene regulation involves transcription factors (TF) that bind to DNA recognition sequences in operon promoters. These recognition sequences, many of which are palindromic, are known as regulatory elements or transcription factor binding sites (TFBS). Some TFs are global regulators that can modulate the expression of hundreds of genes. In this study we examine global regulator half-sites, where a half-site, which we shall call a binding motif (BM), is one half of a palindromic TFBS. We explore the hypothesis that the number of BMs plays an important role in transcriptional regulation, examining empirical data from transcriptional profiling of the CRP and ArcA regulons. We compare the power of BM counts and of full TFBS characteristics to predict induced transcriptional activity. We find that CRP BM counts have a nonlinear effect on CRP-dependent transcriptional activity and predict this activity better than full TFBS quality or location.

  12. Direct and indirect effects of H-NS and Fis on global gene expression control in Escherichia coli

    PubMed Central

    Kahramanoglou, Christina; Seshasayee, Aswin S. N.; Prieto, Ana I.; Ibberson, David; Schmidt, Sabine; Zimmermann, Jurgen; Benes, Vladimir; Fraser, Gillian M.

    2011-01-01

    Nucleoid-associated proteins (NAPs) are global regulators of gene expression in Escherichia coli, which affect DNA conformation by bending, wrapping and bridging the DNA. Two of these—H-NS and Fis—bind to specific DNA sequences and structures. Because of their importance to global gene expression, the binding of these NAPs to the DNA was previously investigated on a genome-wide scale using ChIP-chip. However, variation in their binding profiles across the growth phase and the genome-scale nature of their impact on gene expression remain poorly understood. Here, we present a genome-scale investigation of H-NS and Fis binding to the E. coli chromosome using chromatin immunoprecipitation combined with high-throughput sequencing (ChIP-seq). By performing our experiments under multiple time-points during growth in rich media, we show that the binding regions of the two proteins are mutually exclusive under our experimental conditions. H-NS binds to significantly longer tracts of DNA than Fis, consistent with the linear spread of H-NS binding from high- to surrounding lower-affinity sites; the length of binding regions is associated with the degree of transcriptional repression imposed by H-NS. For Fis, a majority of binding events do not lead to differential expression of the proximal gene; however, it has a significant indirect effect on gene expression partly through its effects on the expression of other transcription factors. We propose that direct transcriptional regulation by Fis is associated with the interaction of tandem arrays of Fis molecules to the DNA and possible DNA bending, particularly at operon-upstream regions. Our study serves as a proof-of-principle for the use of ChIP-seq for global DNA-binding proteins in bacteria, which should become significantly more economical and feasible with the development of multiplexing techniques. PMID:21097887

  13. Does global gene expression analysis in type 2 diabetes provide an opportunity to identify highly promising drug targets?

    PubMed

    Buechler, C; Schäffler, A

    2007-12-01

    The recent technological advances in high-throughput gene expression analysis allow the simultaneous investigation of thousands of genes. These technologies represent promising tools for the identification of new drug targets and considerable progress has been achieved in cancer research where microarray data provide a basis to design new drugs and to predict adverse reactions and the efficacy of chemotherapy. The metabolic syndrome represents a cluster of disorders including high blood pressure, insulin resistance/type 2 diabetes mellitus, visceral obesity and dyslipidaemia with fatty liver disease being a common associated complication. High-throughput gene expression analyses using GeneChips, microarrays and serial analysis of gene expression (SAGE) have been applied to study global gene expression in insulin resistance/type 2 diabetes mellitus. Type 2 diabetes mellitus is a multifactorial and polygenic disease by which several organs are affected. Therefore, the identification of both, disease causing and therapeutically relevant target genes is an ambitious challenge. In the present review we focus on genomic approaches that used biopsies from human skeletal muscle, liver and adipose tissue, the main organs affected by insulin resistance. Members of the PPARgamma coactivator-1 (PGC-1) family of transcriptional coactivators are decreased in skeletal muscle in insulin resistance accounting for the reduced expression of genes involved in mitochondrial oxidative phosphorylation. Hepatic steatosis is also linked to alterations in mitochondrial phosphorylation and oxidative metabolism. An up regulation of pro-inflammatory genes can be detected in early stages of fatty liver disease without histological signs of inflammation. Impaired adipogenesis, intra-adipose accumulation of macrophages and a sustained release of inflammatory and acute phase proteins are characteristic features of adipose tissue in obesity and may aggravate systemic insulin resistance.

  14. Diversity in global gene expression and morphology across a watercress (Nasturtium officinale R. Br.) germplasm collection: first steps to breeding

    PubMed Central

    Payne, Adrienne C.; Clarkson, Graham J.J.; Rothwell, Steve; Taylor, Gail

    2015-01-01

    Watercress (Nasturtium officinale R. Br.) is a nutrient intense, leafy crop that is consumed raw or in soups across the globe, but for which, currently no genomic resources or breeding programme exists. Promising morphological, biochemical and functional genomic variation was identified for the first time in a newly established watercress germplasm collection, consisting of 48 watercress accessions sourced from contrasting global locations. Stem length, stem diameter and anti-oxidant (AO) potential varied across the accessions. This variation was used to identify three extreme contrasting accessions for further analysis. Variation in global gene expression was investigated using an Affymetrix Arabidopsis ATH1 microarray gene chip, using the commercial control (C), an accession selected for dwarf phenotype with a high AO potential (dwarfAO, called ‘Boldrewood’) and one with high AO potential alone. A set of transcripts significantly differentially expressed between these three accessions, were identified, including transcripts involved in the regulation of growth and development and those involved in secondary metabolism. In particular, when differential gene expression was compared between C and dwarfAO, the dwarfAO was characterised by increased expression of genes encoding glucosinolates, which are known precursors of phenethyl isothiocyanate, linked to the anti-carcinogenic effects well-documented in watercress. This study provides the first analysis of natural variation across the watercress genome and has identified important underpinning information for future breeding for enhanced anti-carcinogenic properties and morphology traits in this nutrient-intense crop. PMID:26504575

  15. Global Gene Transcriptome Analysis in Vaccinated Cattle Revealed a Dominant Role of IL-22 for Protection against Bovine Tuberculosis

    PubMed Central

    Villarreal-Ramos, Bernardo; Xing, Zhou; Singh, Mahavir; Vordermeier, H. Martin

    2012-01-01

    Bovine tuberculosis (bTB) is a chronic disease of cattle caused by Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex group of bacteria. Vaccination of cattle might offer a long-term solution for controlling the disease and priority has been given to the development of a cattle vaccine against bTB. Identification of biomarkers in tuberculosis research remains elusive and the goal is to identify host correlates of protection. We hypothesized that by studying global gene expression we could identify in vitro predictors of protection that could help to facilitate vaccine development. Calves were vaccinated with BCG or with a heterologous BCG prime adenovirally vectored subunit boosting protocol. Protective efficacy was determined after M. bovis challenge. RNA was prepared from PPD-stimulated PBMC prepared from vaccinated-protected, vaccinated-unprotected and unvaccinated control cattle prior to M. bovis challenge and global gene expression determined by RNA-seq. 668 genes were differentially expressed in vaccinated-protected cattle compared with vaccinated-unprotected and unvaccinated control cattle. Cytokine-cytokine receptor interaction was the most significant pathway related to this dataset with IL-22 expression identified as the dominant surrogate of protection besides INF-γ. Finally, the expression of these candidate genes identified by RNA-seq was evaluated by RT-qPCR in an independent set of PBMC samples from BCG vaccinated and unvaccinated calves. This experiment confirmed the importance of IL-22 as predictor of vaccine efficacy. PMID:23300440

  16. Diversity in global gene expression and morphology across a watercress (Nasturtium officinale R. Br.) germplasm collection: first steps to breeding.

    PubMed

    Payne, Adrienne C; Clarkson, Graham J J; Rothwell, Steve; Taylor, Gail

    2015-01-01

    Watercress (Nasturtium officinale R. Br.) is a nutrient intense, leafy crop that is consumed raw or in soups across the globe, but for which, currently no genomic resources or breeding programme exists. Promising morphological, biochemical and functional genomic variation was identified for the first time in a newly established watercress germplasm collection, consisting of 48 watercress accessions sourced from contrasting global locations. Stem length, stem diameter and anti-oxidant (AO) potential varied across the accessions. This variation was used to identify three extreme contrasting accessions for further analysis. Variation in global gene expression was investigated using an Affymetrix Arabidopsis ATH1 microarray gene chip, using the commercial control (C), an accession selected for dwarf phenotype with a high AO potential (dwarfAO, called 'Boldrewood') and one with high AO potential alone. A set of transcripts significantly differentially expressed between these three accessions, were identified, including transcripts involved in the regulation of growth and development and those involved in secondary metabolism. In particular, when differential gene expression was compared between C and dwarfAO, the dwarfAO was characterised by increased expression of genes encoding glucosinolates, which are known precursors of phenethyl isothiocyanate, linked to the anti-carcinogenic effects well-documented in watercress. This study provides the first analysis of natural variation across the watercress genome and has identified important underpinning information for future breeding for enhanced anti-carcinogenic properties and morphology traits in this nutrient-intense crop.

  17. Global gene transcriptome analysis in vaccinated cattle revealed a dominant role of IL-22 for protection against bovine tuberculosis.

    PubMed

    Bhuju, Sabin; Aranday-Cortes, Elihu; Villarreal-Ramos, Bernardo; Xing, Zhou; Singh, Mahavir; Vordermeier, H Martin

    2012-12-01

    Bovine tuberculosis (bTB) is a chronic disease of cattle caused by Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex group of bacteria. Vaccination of cattle might offer a long-term solution for controlling the disease and priority has been given to the development of a cattle vaccine against bTB. Identification of biomarkers in tuberculosis research remains elusive and the goal is to identify host correlates of protection. We hypothesized that by studying global gene expression we could identify in vitro predictors of protection that could help to facilitate vaccine development. Calves were vaccinated with BCG or with a heterologous BCG prime adenovirally vectored subunit boosting protocol. Protective efficacy was determined after M. bovis challenge. RNA was prepared from PPD-stimulated PBMC prepared from vaccinated-protected, vaccinated-unprotected and unvaccinated control cattle prior to M. bovis challenge and global gene expression determined by RNA-seq. 668 genes were differentially expressed in vaccinated-protected cattle compared with vaccinated-unprotected and unvaccinated control cattle. Cytokine-cytokine receptor interaction was the most significant pathway related to this dataset with IL-22 expression identified as the dominant surrogate of protection besides INF-γ. Finally, the expression of these candidate genes identified by RNA-seq was evaluated by RT-qPCR in an independent set of PBMC samples from BCG vaccinated and unvaccinated calves. This experiment confirmed the importance of IL-22 as predictor of vaccine efficacy.

  18. Interplay between pathway-specific and global regulation of the fumonisin gene cluster in the rice pathogen Fusarium fujikuroi.

    PubMed

    Rösler, Sarah M; Sieber, Christian M K; Humpf, Hans-Ulrich; Tudzynski, Bettina

    2016-07-01

    The rice pathogenic fungus Fusarium fujikuroi is known to produce a large variety of secondary metabolites. Besides the gibberellins, causing the bakanae effect in infected rice seedlings, the fungus produces several mycotoxins and pigments. Among the 47 putative secondary metabolite gene clusters identified in the genome of F. fujikuroi, the fumonisin gene cluster (FUM) shows very high homology to the FUM cluster of the main fumonisin producer Fusarium verticillioides, a pathogen of maize. Despite the high level of cluster gene conservation, total fumonisin FB1 and FB2 levels (FBx) produced by F. fujikuroi were only 1-10 % compared to F. verticillioides under inducing conditions. Nitrogen repression was found to be relevant for wild-type strains of both species. However, addition of germinated maize kernels activated the FBx production only in F. verticillioides, reflecting the different host specificity of both wild-type strains. Over-expression of the pathway-specific transcription factor Fum21 in F. fujikuroi strongly activated the FUM cluster genes leading to 1000-fold elevated FBx levels. To gain further insights into the nitrogen metabolite repression of FBx biosynthesis, we studied the impact of the global nitrogen regulators AreA and AreB and demonstrated that both GATA-type transcription factors are essential for full activation of the FUM gene cluster. Loss of one of them obstructs the pathway-specific transcription factor Fum21 to fully activate expression of FUM cluster genes.

  19. Effect of transgenes on global gene expression in soybean is within the natural range of variation of conventional cultivars.

    PubMed

    Cheng, K C; Beaulieu, J; Iquira, E; Belzile, F J; Fortin, M G; Strömvik, M V

    2008-05-14

    Current safety assessment for novel crops, including transgenic crops, uses a targeted approach, which relies on compositional analysis. The possibility that transgene expression could lead to unintended effects remains a debated issue. This study used transcriptome profiling as a nontargeted approach to evaluate overall molecular changes in transgenic soybean cultivars. Global gene expression was measured in the first trifoliate leaves of two transgenic and three conventional soybean cultivars using the soybean Affymetrix GeneChip. It was found that gene expression differs more between the two conventional cultivars than between the transgenics and their closest conventional cultivar investigated and that the magnitudes of differences measured in gene expression and genotype (determined by SSR analysis) do not necessarily correlate. A MySQL database coupled with a CGI Web interface was developed to store and present the results ( http://soyxpress.agrenv.mcgill.ca/). By integrating the microarray data with gene annotations and other soybean data, a comprehensive view of differences in gene expression is explored between cultivars.

  20. Global identification of genes regulated by estrogen signaling and demethylation in MCF-7 breast cancer cells.

    PubMed

    Putnik, Milica; Zhao, Chunyan; Gustafsson, Jan-Åke; Dahlman-Wright, Karin

    2012-09-14

    Estrogen signaling and epigenetic modifications, in particular DNA methylation, are involved in regulation of gene expression in breast cancers. Here we investigated a potential regulatory cross-talk between these two pathways by identifying their common target genes and exploring underlying molecular mechanisms in human MCF-7 breast cancer cells. Gene expression profiling revealed that the expression of approximately 140 genes was influenced by both 17β-estradiol (E2) and a demethylating agent 5-aza-2'-deoxycytidine (DAC). Gene ontology (GO) analysis suggests that these genes are involved in intracellular signaling cascades, regulation of cell proliferation and apoptosis. Based on previously reported association with breast cancer, estrogen signaling and/or DNA methylation, CpG island prediction and GO analysis, we selected six genes (BTG3, FHL2, PMAIP1, BTG2, CDKN1A and TGFB2) for further analysis. Tamoxifen reverses the effect of E2 on the expression of all selected genes, suggesting that they are direct targets of estrogen receptor. Furthermore, DAC treatment reactivates the expression of all selected genes in a dose-dependent manner. Promoter CpG island methylation status analysis revealed that only the promoters of BTG3 and FHL2 genes are methylated, with DAC inducing demethylation, suggesting DNA methylation directs repression of these genes in MCF-7 cells. In a further analysis of the potential interplay between estrogen signaling and DNA methylation, E2 treatment showed no effect on the methylation status of these promoters. Additionally, we show that the ERα recruitment occurs at the FHL2 promoter in an E2- and DAC-independent fashion. In conclusion, we identified a set of genes regulated by both estrogen signaling and DNA methylation. However, our data does not support a direct molecular interplay of mediators of estrogen and epigenetic signaling at promoters of regulated genes.

  1. Carbon Monoxide Gas Is Not Inert, but Global, in Its Consequences for Bacterial Gene Expression, Iron Acquisition, and Antibiotic Resistance

    PubMed Central

    Wareham, Lauren K.; Begg, Ronald; Jesse, Helen E.; van Beilen, Johan W.A.; Ali, Salar; Svistunenko, Dimitri; McLean, Samantha; Hellingwerf, Klaas J.; Sanguinetti, Guido

    2016-01-01

    Abstract Aims: Carbon monoxide is a respiratory poison and gaseous signaling molecule. Although CO-releasing molecules (CORMs) deliver CO with temporal and spatial specificity in mammals, and are proven antimicrobial agents, we do not understand the modes of CO toxicity. Our aim was to explore the impact of CO gas per se, without intervention of CORMs, on bacterial physiology and gene expression. Results: We used tightly controlled chemostat conditions and integrated transcriptomic datasets with statistical modeling to reveal the global effects of CO. CO is known to inhibit bacterial respiration, and we found expression of genes encoding energy-transducing pathways to be significantly affected via the global regulators, Fnr, Arc, and PdhR. Aerobically, ArcA—the response regulator—is transiently phosphorylated and pyruvate accumulates, mimicking anaerobiosis. Genes implicated in iron acquisition, and the metabolism of sulfur amino acids and arginine, are all perturbed. The global iron-related changes, confirmed by modulation of activity of the transcription factor Fur, may underlie enhanced siderophore excretion, diminished intracellular iron pools, and the sensitivity of CO-challenged bacteria to metal chelators. Although CO gas (unlike H2S and NO) offers little protection from antibiotics, a ruthenium CORM is a potent adjuvant of antibiotic activity. Innovation: This is the first detailed exploration of global bacterial responses to CO, revealing unexpected targets with implications for employing CORMs therapeutically. Conclusion: This work reveals the complexity of bacterial responses to CO and provides a basis for understanding the impacts of CO from CORMs, heme oxygenase activity, or environmental sources. Antioxid. Redox Signal. 24, 1013–1028. PMID:26907100

  2. Data Mining.

    ERIC Educational Resources Information Center

    Benoit, Gerald

    2002-01-01

    Discusses data mining (DM) and knowledge discovery in databases (KDD), taking the view that KDD is the larger view of the entire process, with DM emphasizing the cleaning, warehousing, mining, and visualization of knowledge discovery in databases. Highlights include algorithms; users; the Internet; text mining; and information extraction.…

  3. Text Mining.

    ERIC Educational Resources Information Center

    Trybula, Walter J.

    1999-01-01

    Reviews the state of research in text mining, focusing on newer developments. The intent is to describe the disparate investigations currently included under the term text mining and provide a cohesive structure for these efforts. A summary of research identifies key organizations responsible for pushing the development of text mining. A section…

  4. HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease.

    PubMed

    Ward, Lucas D; Kellis, Manolis

    2016-01-01

    More than 90% of common variants associated with complex traits do not affect proteins directly, but instead the circuits that control gene expression. This has increased the urgency of understanding the regulatory genome as a key component for translating genetic results into mechanistic insights and ultimately therapeutics. To address this challenge, we developed HaploReg (http://compbio.mit.edu/HaploReg) to aid the functional dissection of genome-wide association study (GWAS) results, the prediction of putative causal variants in haplotype blocks, the prediction of likely cell types of action, and the prediction of candidate target genes by systematic mining of comparative, epigenomic and regulatory annotations. Since first launching the website in 2011, we have greatly expanded HaploReg, increasing the number of chromatin state maps to 127 reference epigenomes from ENCODE 2012 and Roadmap Epigenomics, incorporating regulator binding data, expanding regulatory motif disruption annotations, and integrating expression quantitative trait locus (eQTL) variants and their tissue-specific target genes from GTEx, Geuvadis, and other recent studies. We present these updates as HaploReg v4, and illustrate a use case of HaploReg for attention deficit hyperactivity disorder (ADHD)-associated SNPs with putative brain regulatory mechanisms.

  5. Genome mining of the sordarin biosynthetic gene cluster from Sordaria araneosa Cain ATCC 36386: characterization of cycloaraneosene synthase and GDP-6-deoxyaltrose transferase.

    PubMed

    Kudo, Fumitaka; Matsuura, Yasunori; Hayashi, Takaaki; Fukushima, Masayuki; Eguchi, Tadashi

    2016-07-01

    Sordarin is a glycoside antibiotic with a unique tetracyclic diterpene aglycone structure called sordaricin. To understand its intriguing biosynthetic pathway that may include a Diels-Alder-type [4+2]cycloaddition, genome mining of the gene cluster from the draft genome sequence of the producer strain, Sordaria araneosa Cain ATCC 36386, was carried out. A contiguous 67 kb gene cluster consisting of 20 open reading frames encoding a putative diterpene cyclase, a glycosyltransferase, a type I polyketide synthase, and six cytochrome P450 monooxygenases were identified. In vitro enzymatic analysis of the putative diterpene cyclase SdnA showed that it catalyzes the transformation of geranylgeranyl diphosphate to cycloaraneosene, a known biosynthetic intermediate of sordarin. Furthermore, a putative glycosyltransferase SdnJ was found to catalyze the glycosylation of sordaricin in the presence of GDP-6-deoxy-d-altrose to give 4'-O-demethylsordarin. These results suggest that the identified sdn gene cluster is responsible for the biosynthesis of sordarin. Based on the isolated potential biosynthetic intermediates and bioinformatics analysis, a plausible biosynthetic pathway for sordarin is proposed.

  6. Genome mining of the sordarin biosynthetic gene cluster from Sordaria araneosa Cain ATCC 36386: characterization of cycloaraneosene synthase and GDP-6-deoxyaltrose transferase.

    PubMed

    Kudo, Fumitaka; Matsuura, Yasunori; Hayashi, Takaaki; Fukushima, Masayuki; Eguchi, Tadashi

    2016-07-01

    Sordarin is a glycoside antibiotic with a unique tetracyclic diterpene aglycone structure called sordaricin. To understand its intriguing biosynthetic pathway that may include a Diels-Alder-type [4+2]cycloaddition, genome mining of the gene cluster from the draft genome sequence of the producer strain, Sordaria araneosa Cain ATCC 36386, was carried out. A contiguous 67 kb gene cluster consisting of 20 open reading frames encoding a putative diterpene cyclase, a glycosyltransferase, a type I polyketide synthase, and six cytochrome P450 monooxygenases were identified. In vitro enzymatic analysis of the putative diterpene cyclase SdnA showed that it catalyzes the transformation of geranylgeranyl diphosphate to cycloaraneosene, a known biosynthetic intermediate of sordarin. Furthermore, a putative glycosyltransferase SdnJ was found to catalyze the glycosylation of sordaricin in the presence of GDP-6-deoxy-d-altrose to give 4'-O-demethylsordarin. These results suggest that the identified sdn gene cluster is responsible for the biosynthesis of sordarin. Based on the isolated potential biosynthetic intermediates and bioinformatics analysis, a plausible biosynthetic pathway for sordarin is proposed. PMID:27072286

  7. Functional analysis of Pid3-A4, an ortholog of rice blast resistance gene Pid3 revealed by allele mining in common wild rice.

    PubMed

    Lv, Qiming; Xu, Xiao; Shang, Junjun; Jiang, Guanghuai; Pang, Zhiqian; Zhou, Zhuangzhi; Wang, Jing; Liu, Ya; Li, Ting; Li, Xiaobing; Xu, Jichen; Cheng, Zhukuan; Zhao, Xianfeng; Li, Shigui; Zhu, Lihuang

    2013-06-01

    The rice blast resistance gene Pid3 encodes a nucleotide-binding-site leucine-rich repeat (NBS-LRR) protein. This gene was cloned from the rice 'Digu' (indica) by performing a genome-wide comparison of the NBS-LRR gene family between two genome-sequenced varieties, '9311' (indica) and 'Nipponbare' (japonica). In this study, we performed functional analysis of Pid3-A4, an ortholog of Pid3 revealed by allele mining in the common wild rice A4 (Oryza rufipogon). The predicted protein encoded by Pid3-A4 shares 99.03% sequence identity with Pid3, with only nine amino-acid substitutions. In wild rice plants, Pid3-A4 is constitutively expressed, and its expression is not induced by Magnaporthe oryzae isolate Zhong-10-8-14 infection. Importantly, in transgenic plants, Pid3-A4, as compared with Pid3, displays a distinct resistance spectrum to a set of M. oryzae isolates, including those that prevail in the rice fields of Sichuan Province. Therefore, Pid3-A4 should be quite useful for the breeding of rice blast resistance, especially in southwestern China.

  8. Global identification of genes regulated by estrogen signaling and demethylation in MCF-7 breast cancer cells

    SciTech Connect

    Putnik, Milica; Zhao, Chunyan; Gustafsson, Jan-Ake; Dahlman-Wright, Karin

    2012-09-14

    Highlights: Black-Right-Pointing-Pointer Estrogen signaling and demethylation can both control gene expression in breast cancers. Black-Right-Pointing-Pointer Cross-talk between these mechanisms is investigated in human MCF-7 breast cancer cells. Black-Right-Pointing-Pointer 137 genes are influenced by both 17{beta}-estradiol and demethylating agent 5-aza-2 Prime -deoxycytidine. Black-Right-Pointing-Pointer A set of genes is identified as targets of both estrogen signaling and demethylation. Black-Right-Pointing-Pointer There is no direct molecular interplay of mediators of estrogen and epigenetic signaling. -- Abstract: Estrogen signaling and epigenetic modifications, in particular DNA methylation, are involved in regulation of gene expression in breast cancers. Here we investigated a potential regulatory cross-talk between these two pathways by identifying their common target genes and exploring underlying molecular mechanisms in human MCF-7 breast cancer cells. Gene expression profiling revealed that the expression of approximately 140 genes was influenced by both 17{beta}-estradiol (E2) and a demethylating agent 5-aza-2 Prime -deoxycytidine (DAC). Gene ontology (GO) analysis suggests that these genes are involved in intracellular signaling cascades, regulation of cell proliferation and apoptosis. Based on previously reported association with breast cancer, estrogen signaling and/or DNA methylation, CpG island prediction and GO analysis, we selected six genes (BTG3, FHL2, PMAIP1, BTG2, CDKN1A and TGFB2) for further analysis. Tamoxifen reverses the effect of E2 on the expression of all selected genes, suggesting that they are direct targets of estrogen receptor. Furthermore, DAC treatment reactivates the expression of all selected genes in a dose-dependent manner. Promoter CpG island methylation status analysis revealed that only the promoters of BTG3 and FHL2 genes are methylated, with DAC inducing demethylation, suggesting DNA methylation directs repression of

  9. A Global Analysis of the Polygalacturonase Gene Family in Soybean (Glycine max)

    PubMed Central

    Wang, Feifei; Sun, Xia; Shi, Xinyi; Zhai, Hong; Tian, Changen; Kong, Fanjiang; Liu, Baohui; Yuan, Xiaohui

    2016-01-01

    Polygalacturonase is one of the pectin hydrolytic enzymes involved in various developmental and physiological processes such as seed germination, organ abscission, pod and anther dehiscence, and xylem cell formation. To date, no systematic analysis of polygalacturonase incorporating genome organization, gene structure, and expression profiling has been conducted in soybean (Glycine max var. Williams 82). In this study, we identified 112 GmPG genes from the soybean Wm82.a2v1 genome. These genes were classified into three groups, group I (105 genes), group II (5 genes), and group III (2 genes). Fifty-four pairs of duplicate paralogous genes were preferentially identified from duplicated regions of the soybean genome, which implied that long segmental duplications significantly contributed to the expansion of the GmPG gene family. Moreover, GmPG transcripts were analyzed in various tissues using RNA-seq data. The results showed the differential expression of 64 GmPGs in the tissue and partially redundant expression of some duplicate genes, while others showed functional diversity. These findings suggested that the GmPGs were retained by substantial subfunctionalization during the soybean evolutionary processes. Finally, evolutionary analysis based on single nucleotide polymorphisms (SNPs) in wild and cultivated soybeans revealed that 107 GmPGs had selected site(s), which indicated that these genes may have undergone strong selection during soybean domestication. Among them, one non-synonymous SNP of GmPG031 affected floral development during selection, which was consistent with the results of RNA-seq and evolutionary analyses. Thus, our results contribute to the functional characterization of GmPG genes in soybean. PMID:27657691

  10. First cellular approach of the effects of global warming on groundwater organisms: a study of the HSP70 gene expression.

    PubMed

    Colson-Proch, Céline; Morales, Anne; Hervant, Frédéric; Konecny, Lara; Moulin, Colette; Douady, Christophe J

    2010-05-01

    Whereas the consequences of global warming at population or community levels are well documented, studies at the cellular level are still scarce. The study of the physiological or metabolic effects of such small increases in temperature (between +2 degrees C and +6 degrees C) is difficult because they are below the amplitude of the daily or seasonal thermal variations occurring in most environments. In contrast, subterranean biotopes are highly thermally buffered (+/-1 degrees C within a year), and underground water organisms could thus be particularly well suited to characterise cellular responses of global warming. To this purpose, we studied genes encoding chaperone proteins of the HSP70 family in amphipod crustaceans belonging to the ubiquitous subterranean genus Niphargus. An HSP70 sequence was identified in eight populations of two complexes of species of the Niphargus genus (Niphargus rhenorhodanensis and Niphargus virei complexes). Expression profiles were determined for one of these by reverse transcription and quantitative polymerase chain reaction, confirming the inducible nature of this gene. An increase in temperature of 2 degrees C seemed to be without effect on N. rhenorhodanensis physiology, whereas a heat shock of +6 degrees C represented an important thermal stress for these individuals. Thus, this study shows that although Niphargus individuals do not undergo any daily or seasonal thermal variations in underground water, they display an inducible HSP70 heat shock response. This controlled laboratory-based physiological experiment constitutes a first step towards field investigations of the cellular consequences of global warming on subterranean organisms.

  11. Suppressing Sorbitol Synthesis Substantially Alters the Global Expression Profile of Stress Response Genes in Apple (Malus domestica) Leaves.

    PubMed

    Wu, Ting; Wang, Yi; Zheng, Yi; Fei, Zhangjun; Dandekar, Abhaya M; Xu, Kenong; Han, Zhenhai; Cheng, Lailiang

    2015-09-01

    Sorbitol is a major product of photosynthesis in apple (Malus domestica) that is involved in carbohydrate metabolism and stress tolerance. However, little is known about how the global transcript levels in apple leaves respond to decreased sorbitol synthesis. In this study we used RNA sequencing (RNA-seq) profiling to characterize the transcriptome of leaves from transgenic lines of the apple cultivar 'Greensleeves' exhibiting suppressed expression of aldose-6-phosphate reductase (A6PR) to gain insights into sorbitol function and the consequences of decreased sorbitol synthesis on gene expression. We observed that, although the leaves of the low sorbitol transgenic lines accumulate higher levels of various primary metabolites, only very limited changes were found in the levels of transcripts associated with primary metabolism. We suggest that this is indicative of post-transcriptional and/or post-translational regulation of primary metabolite accumulation and central carbon metabolism. However, we identified significantly enriched gene ontology terms belonging to the 'stress related process' category in the antisense lines (P-value < 0.05). These include genes involved in the synthesis/degradation of abscisic acid, salicylic acid and jasmonic acid, nucleotide-binding site leucine-rich repeat (NBS-LRR) disease resistance genes and ATP-binding cassette (ABC) transporter genes. This suggests that sorbitol plays a role in the responses of apple trees to abiotic and biotic stresses. PMID:26076968

  12. Global gene expression analysis of Saccharomyces cerevisiae grown under redox potential-controlled very-high-gravity conditions.

    PubMed

    Liu, Chen-Guang; Lin, Yen-Han; Bai, Feng-Wu

    2013-11-01

    Redox potential (ORP) plays a pivotal role in yeast viability and ethanol production during very-high-gravity (VHG) ethanol fermentation. In order to identify the correlation between redox potential profiles and gene expression patterns, global gene expression of Saccharomyces cerevisiae was investigated. Results indicated that significant changes in gene expression occurred at the periods of 0 - 6 h and 30 - 36 h, respectively. Changes noted in the period of 0 - 6 h were mainly related to carbohydrate metabolism. In contrast, gene expression variation at 30 - 36 h could be attributed primarily to stress response. Although CDC19 was down-regulated, expression of PYK2, PDC6 and ADH2 correlated inversely with ORP. Meanwhile, expression of GPD1 decreased due to the depletion of dissolved oxygen in the fermentation broth, but expression of GPD2 correlated with ORP. Transcription of genes encoding heat shock proteins was characterized by uphill, downhill, valley and plateau expression profiles, accordingly to specific function in stress response. These results highlight the role of ORP in modulating yeast physiology and metabolism under VHG conditions.

  13. Remodeling of global transcription patterns of Cryptococcus neoformans genes mediated by the stress-activated HOG signaling pathways.

    PubMed

    Ko, Young-Joon; Yu, Yeong Man; Kim, Gyu-Bum; Lee, Gir-Won; Maeng, Pil Jae; Kim, Sangsoo; Floyd, Anna; Heitman, Joseph; Bahn, Yong-Sun

    2009-08-01

    The ability to sense and adapt to a hostile host environment is a crucial element for virulence of pathogenic fungi, including Cryptococcus neoformans. These cellular responses are evoked by diverse signaling cascades, including the stress-activated HOG pathway. Despite previous analysis of central components of the HOG pathway, its downstream signaling network is poorly characterized in C. neoformans. Here we performed comparative transcriptome analysis with HOG signaling mutants to explore stress-regulated genes and their correlation with the HOG pathway in C. neoformans. In this study, we not only provide important insights into remodeling patterns of global gene expression for counteracting external stresses but also elucidate novel characteristics of the HOG pathway in C. neoformans. First, inhibition of the HOG pathway increases expression of ergosterol biosynthesis genes and cellular ergosterol content, conferring a striking synergistic antifungal activity with amphotericin B and providing an excellent opportunity to develop a novel therapeutic method for treatment of cryptococcosis. Second, a number of cadmium-sensitive genes are differentially regulated by the HOG pathway, and their mutation causes resistance to cadmium. Finally, we have discovered novel stress defense and HOG-dependent genes, which encode a sodium/potassium efflux pump, protein kinase, multidrug transporter system, and elements of the ubiquitin-dependent system.

  14. Suppressing Sorbitol Synthesis Substantially Alters the Global Expression Profile of Stress Response Genes in Apple (Malus domestica) Leaves.

    PubMed

    Wu, Ting; Wang, Yi; Zheng, Yi; Fei, Zhangjun; Dandekar, Abhaya M; Xu, Kenong; Han, Zhenhai; Cheng, Lailiang

    2015-09-01

    Sorbitol is a major product of photosynthesis in apple (Malus domestica) that is involved in carbohydrate metabolism and stress tolerance. However, little is known about how the global transcript levels in apple leaves respond to decreased sorbitol synthesis. In this study we used RNA sequencing (RNA-seq) profiling to characterize the transcriptome of leaves from transgenic lines of the apple cultivar 'Greensleeves' exhibiting suppressed expression of aldose-6-phosphate reductase (A6PR) to gain insights into sorbitol function and the consequences of decreased sorbitol synthesis on gene expression. We observed that, although the leaves of the low sorbitol transgenic lines accumulate higher levels of various primary metabolites, only very limited changes were found in the levels of transcripts associated with primary metabolism. We suggest that this is indicative of post-transcriptional and/or post-translational regulation of primary metabolite accumulation and central carbon metabolism. However, we identified significantly enriched gene ontology terms belonging to the 'stress related process' category in the antisense lines (P-value < 0.05). These include genes involved in the synthesis/degradation of abscisic acid, salicylic acid and jasmonic acid, nucleotide-binding site leucine-rich repeat (NBS-LRR) disease resistance genes and ATP-binding cassette (ABC) transporter genes. This suggests that sorbitol plays a role in the responses of apple trees to abiotic and biotic stresses.

  15. Global profiling of influence of intra-ischemic brain temperature on gene expression in rat brain.

    PubMed

    Kobayashi, Megumi Sugahara; Asai, Satoshi; Ishikawa, Koichi; Nishida, Yayoi; Nagata, Toshihito; Takahashi, Yasuo

    2008-06-01

    Mild to moderate differences in brain temperature are known to greatly affect the outcome of cerebral ischemia. The impact of brain temperature on ischemic disorders has been mainly evaluated through pathological analysis. However, no comprehensive analyses have been conducted at the gene expression level. Using a high-density oligonucleotide microarray, we screened 24000 genes in the hippocampus under hypothermic (32 degrees C), normothermic (37 degrees C), and hyperthermic (39 degrees C) conditions in a rat ischemia-reperfusion model. When the ischemic group at each intra-ischemic brain temperature was compared to a sham-operated control group, genes whose expression levels changed more than three-fold with statistical significance could be detected. In our screening condition, thirty-three genes (some of them novel) were obtained after screening, and extensive functional surveys and literature reviews were subsequently performed. In the hypothermic condition, many neuroprotective factor genes were obtained, whereas cell death- and cell damage-associated genes were detected as the brain temperature increased. At all intra-ischemic brain temperatures, multiple molecular chaperone genes were obtained. The finding that intra-ischemic brain temperature affects the expression level of many genes related to neuroprotection or neurotoxicity coincides with the different pathological outcomes at different brain temperatures, demonstrating the utility of the genetic approach.

  16. Genetic Variation at the N-acetyltransferase (NAT) Genes in Global Populations

    EPA Science Inventory

    Functional variability at the N-acetyltransferase (NAT) genes is associated with adverse drug reactions and cancer susceptibility in humans. Previous studies of small sets of ethnic groups have indicated that the NAT genes have high levels of amino acid variation that differ in f...

  17. Changes in global gene expression in rat myometrium in transition from late pregnancy to parturition.

    PubMed

    Helguera, Gustavo; Eghbali, Mansoureh; Sforza, Daniel; Minosyan, Tamara Y; Toro, Ligia; Stefani, Enrico

    2009-01-01

    The process of parturition involves the complex interplay of factors that change the excitability and contractile activity of the uterus. We have compared the relative gene expression profile of myometrium from rats before parturition (21 days pregnant) and during delivery, using high-density DNA microarray. Of 8,740 sequences available in the array, a total of 3,782 were detected as present. From the sequences that were significantly altered, 59 genes were upregulated and 82 genes were downregulated. We were able to detect changes in genes described to have altered expression level at term, including connexin 43 and 26, cyclooxygenase 2, and oxytocin receptor, as well as novel genes that have been not previously associated with parturition. Quantitative real-time PCR on selected genes further confirmed the microarray data. Here we report for the first time that aquaporin5 (AQP5), a member of the aquaporin water channel family, was dramatically downregulated during parturition (approximately 100-fold by microarray and approximately 50-fold by real-time PCR). The emerging profile highlights biochemical cascades occurring in a period of approximately 36 h that trigger parturition and the initiation of myometrium reverse remodeling postpartum. The microarray analysis uncovered genes that were previously suspected to play a role in parturition. This regulation involves genes from immune/inflammatory response, steroid/lipid metabolism, calcium homeostasis, cell volume regulation, cell signaling, cell division, and tissue remodeling, suggesting the presence of multiple and redundant mechanisms altered in the process of birth.

  18. Global correlation analysis for microRNA and gene expression profiles in human obesity.

    PubMed

    Li, Jiayu; Zhou, Changyu; Li, Jiarui; Su, Ziyuan; Sang, Haiyan; Jia, Erna; Si, Daoyuan

    2015-05-01

    Obesity is an increasing health problem associated with major adverse consequences for human health. MicroRNAs (miRNAs), small endogenous non-coding RNAs, regulate the expression of genes that play roles in human body via posttranscriptional inhibition. To identify the miRNAs and their target genes involved in obesity, we downloaded the miRNA and gene expression profiles from gene expression omnibus (GEO) database and analyzed the differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) in adipose tissues from obese subjects compared to those from non-obese subjects. Then, we constructed the miRNA-target interaction network and conducted functional enrichment analysis of DEGs, and the targets negatively correlated with DEMs. We identified a total of 16 miRNAs and 192 genes that showed a significantly different expression and 3002 miRNA-target interaction pairs, including 182 regulatory pairs in obesity. Target genes of DEMs were found mainly enriched in several functions, such as collagen fibril organization, extracellular matrix part, and extracellular matrix structural constituent. Moreover, hsa-miR-425 and hsa-miR-126 had a significant number of target genes and hsa-miR-16/COL12A1 and hsa-miR-634/SLC4A4 interaction pairs are significantly co-expressed, suggesting that they might play important roles in the pathogenesis of obesity. Our study provides a bioinformatic basis for further research of molecular mechanism in obesity.

  19. Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain

    PubMed Central

    Montoya, Julio Cesar; Fajardo, Dianora; Peña, Angela; Sánchez, Adalberto; Domínguez, Martha C; Satizábal, José María

    2014-01-01

    Background: The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. Objective: To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. Methods: There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. Results: Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously identified brain structures play a crucial role in the learning process, in different class of memory and in motor skills. Conclusion: The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition. PMID:25767303

  20. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis

    NASA Astrophysics Data System (ADS)

    Kaminski, Naftali; Allard, John D.; Pittet, Jean F.; Zuo, Fengrong; Griffiths, Mark J. D.; Morris, David; Huang, Xiaozhu; Sheppard, Dean; Heller, Renu A.

    2000-02-01

    The molecular mechanisms of pulmonary fibrosis are poorly understood. We have used oligonucleotide arrays to analyze the gene expression programs that underlie pulmonary fibrosis in response to bleomycin, a drug that causes lung inflammation and fibrosis, in two strains of susceptible mice (129 and C57BL/6). We then compared the gene expression patterns in these mice with 129 mice carrying a null mutation in the epithelial-restricted integrin 6 subunit (6/-), which develop inflammation but are protected from pulmonary fibrosis. Cluster analysis identified two distinct groups of genes involved in the inflammatory and fibrotic responses. Analysis of gene expression at multiple time points after bleomycin administration revealed sequential induction of subsets of genes that characterize each response. The availability of this comprehensive data set should accelerate the development of more effective strategies for intervention at the various stages in the development of fibrotic diseases of the lungs and other organs.

  1. The use of glass beads cultivation system to study the global effect of the ppk gene inactivation in Streptomyces lividans.

    PubMed

    Nezbedová, S; Bezoušková, S; Kofroňová, O; Benada, O; Rehulka, P; Rehulková, H; Goldová, J; Janeček, J; Weiser, J

    2011-11-01

    The glass beads cultivation system developed in our laboratory for physiological studies of filamentous microorganisms supports differentiation and allows complete recovery of bacterial colonies and their natural products from cultivation plates. Here, we used this system to study the global effect of ppk gene disruption in Streptomyces lividans. The ppk encoding the enzyme polyphosphate kinase (P) catalyses the reversible polymerisation of gamma phosphate of ATP to polyphosphates. The resulting are phosphate and energy stock polymers. Because P activity impacts the overall energetic state of the cell, it is also connected to secondary metabolite (e.g. antibiotic) biosynthesis. We analysed the global effects of the disruption of this gene including its influence on the production of pigmented antibiotics, on morphological differentiation, on the levels of ATP and on the whole cytoplasmic protein expression pattern of S. lividans. We observed that the S. lividans ppk mutant produced antibiotics earlier and in greater amount than the wild-type (wt) strain. On the other hand, we did not observe any obvious effect on colony morphological development. In agreement with the function of Ppk, we detected much lower levels of ATP in ppk- mutant than in the wt strain. Proteomic analysis revealed that the genes that were influenced by ppk inactivation included enzymes involved in carbon or nitrogen metabolism, phosphate transport and components of the cell translational machinery. We showed that the synthesis of translation elongation factor Tu is during sporulation much higher in ppk- mutant than in wild-type strain.

  2. Global Gene Expression Changes in Rat Retinal Ganglion Cells in Experimental Glaucoma

    PubMed Central

    Wang, Dan Yi; Ray, Arjun; Rodgers, Kathryn; Ergorul, Ceren; Hyman, Bradley T.; Huang, Wei

    2010-01-01

    Purpose. Intraocular pressure (IOP) is an important risk factor in glaucoma. Gene expression changes were studied in glaucomatous rat retinal ganglion cells (RGCs) to elucidate altered transcriptional pathways. Methods. RGCs were back-labeled with Fluorogold. Unilateral IOP elevation was produced by injection of hypertonic saline into the episcleral veins. Laser capture microdissection (LCM) was used to capture an equal number of RGCs from normal and glaucomatous retinal sections. RNA was extracted and amplified, labeled, and hybridized to rat genome microarrays, and data analysis was performed. After selected microarray data were confirmed by RT-qPCR and immunohistochemistry, biological pathway analyses were performed. Results. Significant changes were found in the expression of 905 genes, with 330 genes increasing and 575 genes decreasing in glaucomatous RGCs. Multiple cellular pathways were involved. Ingenuity pathway analysis demonstrated significant changes in cardiac β-adrenergic signaling, interferon signaling, glutamate receptor signaling, cAMP-mediated signaling, chemokine signaling, 14-3-3-mediated signaling, and G-protein-coupled receptor signaling. Gene set enrichment analysis showed that the genes involved in apoptotic pathways were enriched in glaucomatous RGCs. The prosurvival gene Stat3 was upregulated in response to elevated IOP, and immunohistochemistry confirmed that Stat3 and phosphorylated-Stat3 levels were increased in RGCs in experimental glaucoma. In addition, the expression of several prosurvival genes normally expressed in RGCs was decreased. Conclusions. There are extensive changes in gene expression in glaucomatous RGCs involving multiple molecular pathways, including prosurvival and prodeath genes. The alteration in the balance between prosurvival and prodeath may contribute to RGC death in glaucoma. PMID:20335623

  3. Identification of gene regulation patterns underlying both E2- and tamoxifen-stimulated cell growth through global gene expression profiling in breast cancer cells

    PubMed Central

    Fan, Ping; Cunliffe, Heather E.; Griffith, Obi L.; Agboke, Fadeke A.; Ramos, Pilar; Gray, Joe W.; Jordan, V. Craig

    2014-01-01

    Purpose A c-Src inhibitor blocks estrogen (E2)-induced stress and converts E2 responses from inducing apoptosis to growth stimulation in E2-deprived breast cancer cells. A reprogrammed cell line, MCF-7:PF, results in a functional estrogen receptor (ER). We addressed the question of whether the selective ER modulator 4-hydroxytamoxifen (4-OHT) could target ER to prevent E2-stimulated growth in MCF-7:PF cells. Methods Expression of mRNA was measured through real-time RT-PCR. Global gene expression profile was analyzed through microarray. Transcriptome profiles were screened by RNA-sequencing. Results Unexpectedly, both 4-OHT and E2 stimulated cell growth in a concentration-dependent manner. Expression profiling showed a remarkable overlap in genes regulated in the same direction by E2 and 4-OHT. Pathway enrichment analysis of the 280 genes commonly deregulated in MCF-7:PF cells by 4-OHT and E2 revealed functions mainly related to membrane, cytoplasm, and metabolic processes. Further analysis of 98 genes up-regulated by both 4-OHT and E2 uncovered a significant enrichment in genes associated with membrane remodeling, cytoskeleton reorganization, cytoplasmic adapter proteins, cytoplasm organelles proteins, and related processes. 4-OHT was more potent than E2 in up-regulating some membrane remodeling molecules, such as EHD2, FHL2, HOMER3 and RHOF. In contrast, 4-OHT acted as an antagonist to inhibit expression of the majority of enriched membrane-associated genes in wild-type MCF-7 cells. Conclusions Long-term selection pressure has changed the cell population responses to 4-OHT. Membrane-associated signaling is critical for 4-OHT-stimulated cell growth in MCF-7:PF cells. This study provides a rationale for the further investigation of target therapy for tamoxifen resistant patients. PMID:25212499

  4. Differential evolutionary rates of neuronal transcriptome in Aplysia kurodai and Aplysia californica as a tool for gene mining.

    PubMed

    Choi, Sun-Lim; Lee, Yong-Seok; Rim, Young-Soo; Kim, Tae-Hyung; Moroz, Leonid L; Kandel, Eric R; Bhak, Jong; Kaang, Bong-Kiun

    2010-07-01

    The marine mollusk Aplysia is a fascinating model organism for studying molecular mechanisms underlying learning and memory. However, evolutionary studies about Aplysia have been limited by the lack of its genomic information. Recently, large-scale expressed sequence tag (EST) databases have been acquired by sequencing cDNA libraries from A. californica and A. kurodai. The closeness between the two species allowed us to investigate rapidly evolving genes by comparing their orthologs. Using this method, we found that a subset of signal transduction genes in neurons showed rates of protein evolution higher than those of housekeeping genes. Moreover, we were also able to find several candidate genes that may be involved in learning and memory or synaptic plasticity among genes showing relatively higher K(a)/K(s) ratios. We also investigated the relationship between evolutionary rates and tissue distribution of Aplysia genes. They propose that the estimation of evolutionary rates cannot be a good marker to assess neuronal expression; however, it still can be an efficient way to narrow down the pool of candidate genes involved in neuronal functions for the further studies. PMID:20536287

  5. Mining the key regulatory genes of chicken inosine 5'-monophosphate metabolism based on time series microarray data.

    PubMed

    Ma, Teng; Xu, Lu; Wang, Hongzhi; Chen, Jing; Liu, Lu; Chang, Guobin; Chen, Guohong

    2015-01-01

    IMP (inosine 5'-monophosphate) is a compound that enhances the flavor of poultry meat. IMP has become a new breeding trait to improve poultry meat quality. We tried to identify several potential regulatory genes, and construct their predicted regulatory relationships. Time series gene expression profiles of thigh muscle tissues of Rugao chicken, a famous indigenous breed in China, were performed for analysis of genes that are co-expressed or correlated with the concentration of IMP. We found 15 crucial co-expression genes, which are Hspa2, Pten, Gabpa, Bpi, Mkl1, Srf, Cd34, Hspa4, Etv6, Bmpr2, Gde1, Igfbp5, Cd28, Pecam1 and Gja1, that may directly or indirectly regulate IMP metabolism. Eventually, we computed the correlation coefficient between 19 IMP Genes and 15 CGs (15 co-expression genes), and we identified and constructed a predicted regulation network. In conclusion, variation of IMP concentration was primarily connected with the muscle development process. During this process, 15 CGs were identified that may have significant influence on IMP metabolism. In particular, Bmpr2, Pten and co-expression genes correlated with Entpd8 might play important roles in regulating IMP de novo synthesis, decomposition and salvage synthesis.

  6. Enriching regulatory networks by bootstrap learning using optimised GO-based gene similarity and gene links mined from PubMed abstracts

    SciTech Connect

    Taylor, Ronald C.; Sanfilippo, Antonio P.; McDermott, Jason E.; Baddeley, Robert L.; Riensche, Roderick M.; Jensen, Russell S.; Verhagen, Marc; Pustejovsky, James

    2011-02-18

    Transcriptional regulatory networks are being determined using “reverse engineering” methods that infer connections based on correlations in gene state. Corroboration of such networks through independent means such as evidence from the biomedical literature is desirable. Here, we explore a novel approach, a bootstrapping version of our previous Cross-Ontological Analytic method (XOA) that can be used for semi-automated annotation and verification of inferred regulatory connections, as well as for discovery of additional functional relationships between the genes. First, we use our annotation and network expansion method on a biological network learned entirely from the literature. We show how new relevant links between genes can be iteratively derived using a gene similarity measure based on the Gene Ontology that is optimized on the input network at each iteration. Second, we apply our method to annotation, verification, and expansion of a set of regulatory connections found by the Context Likelihood of Relatedness algorithm.

  7. Global Analysis of Predicted G Protein−Coupled Receptor Genes in the Filamentous Fungus, Neurospora crassa

    PubMed Central

    Cabrera, Ilva E.; Pacentine, Itallia V.; Lim, Andrew; Guerrero, Nayeli; Krystofova, Svetlana; Li, Liande; Michkov, Alexander V.; Servin, Jacqueline A.; Ahrendt, Steven R.; Carrillo, Alexander J.; Davidson, Liza M.; Barsoum, Andrew H.; Cao, Jackie; Castillo, Ronald; Chen, Wan-Ching; Dinkchian, Alex; Kim, Stephanie; Kitada, Sho M.; Lai, Taffani H.; Mach, Ashley; Malekyan, Cristin; Moua, Toua R.; Torres, Carlos Rojas; Yamamoto, Alaina; Borkovich, Katherine A.

    2015-01-01

    G protein−coupled receptors (GPCRs) regulate facets of growth, development, and environmental sensing in eukaryotes, including filamentous fungi. The largest predicted GPCR class in these organisms is the Pth11-related, with members similar to a protein required for disease in the plant pathogen Magnaporthe oryzae. However, the Pth11-related class has not been functionally studied in any filamentous fungal species. Here, we analyze phenotypes in available mutants for 36 GPCR genes, including 20 Pth11-related, in the model filamentous fungus Neurospora crassa. We also investigate patterns of gene expression for all 43 predicted GPCR genes in available datasets. A total of 17 mutants (47%) possessed at least one growth or developmental phenotype. We identified 18 mutants (56%) with chemical sensitivity or nutritional phenotypes (11 uniquely), bringing the total number of mutants with at least one defect to 28 (78%), including 15 mutants (75%) in the Pth11-related class. Gene expression trends for GPCR genes correlated with the phenotypes observed for many mutants and also suggested overlapping functions for several groups of co-transcribed genes. Several members of the Pth11-related class have phenotypes and/or are differentially expressed on cellulose, suggesting a possible role for this gene family in plant cell wall sensing or utilization. PMID:26464358

  8. Global Analysis of Predicted G Protein-Coupled Receptor Genes in the Filamentous Fungus, Neurospora crassa.

    PubMed

    Cabrera, Ilva E; Pacentine, Itallia V; Lim, Andrew; Guerrero, Nayeli; Krystofova, Svetlana; Li, Liande; Michkov, Alexander V; Servin, Jacqueline A; Ahrendt, Steven R; Carrillo, Alexander J; Davidson, Liza M; Barsoum, Andrew H; Cao, Jackie; Castillo, Ronald; Chen, Wan-Ching; Dinkchian, Alex; Kim, Stephanie; Kitada, Sho M; Lai, Taffani H; Mach, Ashley; Malekyan, Cristin; Moua, Toua R; Torres, Carlos Rojas; Yamamoto, Alaina; Borkovich, Katherine A

    2015-10-13

    G protein-coupled receptors (GPCRs) regulate facets of growth, development, and environmental sensing in eukaryotes, including filamentous fungi. The largest predicted GPCR class in these organisms is the Pth11-related, with members similar to a protein required for disease in the plant pathogen Magnaporthe oryzae. However, the Pth11-related class has not been functionally studied in any filamentous fungal species. Here, we analyze phenotypes in available mutants for 36 GPCR genes, including 20 Pth11-related, in the model filamentous fungus Neurospora crassa. We also investigate patterns of gene expression for all 43 predicted GPCR genes in available datasets. A total of 17 mutants (47%) possessed at least one growth or developmental phenotype. We identified 18 mutants (56%) with chemical sensitivity or nutritional phenotypes (11 uniquely), bringing the total number of mutants with at least one defect to 28 (78%), including 15 mutants (75%) in the Pth11-related class. Gene expression trends for GPCR genes correlated with the phenotypes observed for many mutants and also suggested overlapping functions for several groups of co-transcribed genes. Several members of the Pth11-related class have phenotypes and/or are differentially expressed on cellulose, suggesting a possible role for this gene family in plant cell wall sensing or utilization.

  9. Global Analysis of Predicted G Protein-Coupled Receptor Genes in the Filamentous Fungus, Neurospora crassa.

    PubMed

    Cabrera, Ilva E; Pacentine, Itallia V; Lim, Andrew; Guerrero, Nayeli; Krystofova, Svetlana; Li, Liande; Michkov, Alexander V; Servin, Jacqueline A; Ahrendt, Steven R; Carrillo, Alexander J; Davidson, Liza M; Barsoum, Andrew H; Cao, Jackie; Castillo, Ronald; Chen, Wan-Ching; Dinkchian, Alex; Kim, Stephanie; Kitada, Sho M; Lai, Taffani H; Mach, Ashley; Malekyan, Cristin; Moua, Toua R; Torres, Carlos Rojas; Yamamoto, Alaina; Borkovich, Katherine A

    2015-12-01

    G protein-coupled receptors (GPCRs) regulate facets of growth, development, and environmental sensing in eukaryotes, including filamentous fungi. The largest predicted GPCR class in these organisms is the Pth11-related, with members similar to a protein required for disease in the plant pathogen Magnaporthe oryzae. However, the Pth11-related class has not been functionally studied in any filamentous fungal species. Here, we analyze phenotypes in available mutants for 36 GPCR genes, including 20 Pth11-related, in the model filamentous fungus Neurospora crassa. We also investigate patterns of gene expression for all 43 predicted GPCR genes in available datasets. A total of 17 mutants (47%) possessed at least one growth or developmental phenotype. We identified 18 mutants (56%) with chemical sensitivity or nutritional phenotypes (11 uniquely), bringing the total number of mutants with at least one defect to 28 (78%), including 15 mutants (75%) in the Pth11-related class. Gene expression trends for GPCR genes correlated with the phenotypes observed for many mutants and also suggested overlapping functions for several groups of co-transcribed genes. Several members of the Pth11-related class have phenotypes and/or are differentially expressed on cellulose, suggesting a possible role for this gene family in plant cell wall sensing or utilization. PMID:26464358

  10. Effect of light on global gene expression in the neuroglobin-deficient mouse retina

    PubMed Central

    ILMJÄRV, STEN; REIMETS, RIIN; HUNDAHL, CHRISTIAN ANSGAR; LUUK, HENDRIK

    2014-01-01

    Several previous studies have raised controversy over the functional role of neuroglobin (Ngb) in the retina. Certain studies indicate a significant impact of Ngb on retinal physiology, whereas others are conflicting. The present is an observational study that tested the effect of Ngb deficiency on gene expression in dark- and light-adapted mouse retinas. Large-scale gene expression profiling was performed using GeneChip® Mouse Exon 1.0 ST arrays and the results were compared to publicly available data sets. The lack of Ngb was found to have a minor effect on the light-induced retinal gene expression response. In addition, there was no increase in the expression of marker genes associated with hypoxia, endoplasmic reticulum-stress and oxidative stress in the Ngb-deficient retina. By contrast, several genes were identified that appeared to be differentially expressed between the genotypes when the effect of light was ignored. The present study indicates that Ngb deficiency does not lead to major alternations in light-dependent gene expression response, but leads to subtle systemic differences of a currently unknown functional significance. PMID:25279145

  11. Global Transcriptome Analysis and Identification of the Flowering Regulatory Genes Expressed in Leaves of Lagerstroemia indica

    PubMed Central

    Zhang, Zhenyu; Wang, Peng; Ma, Lingling; Li, Linfang; Yang, Rutong; Ma, Yuzhu; Wang, Shu'an; Wang, Qing

    2014-01-01

    Flowering time is an important trait for ornamental plants, and flowering regulation has thus been both a focus of and challenge to researchers. Lagerstroemia indica is an important summer flowering tree in China and has been introduced abroad as a key parent of new cultivars; no previous reports have addressed the regulation of flowering time in this species. In this study, 28,567,778×2 reads were obtained from leaves of L. indica. A total of 37,325 unigenes were assembled with an average length of 849.56 bp, and 17,506 (46.90%) unigenes were significantly matched to known genes in the nr database of GenBank. The annotated sequences were clustered into putative functional categories using the Gene Ontology framework. Potential genes and their functions were predicted by the Cluster of Orthologous Groups analysis and Kyoto Encyclopedia of Genes and Genomes pathway mapping. A total of 115 unigenes related to flowering time control were discovered. Ten homologous genes of the CONSTANS-like (COL) gene family were identified based on transcript data. Phylogenetic analysis of the CONSTANS and COL genes from L. indica and other species grouped them into three clades. The transcriptome dataset and outcome of the analysis provide a valuable new resource for research on the functional genomics and molecular mechanisms of flowering control in L. indica. PMID:24983664

  12. Systematic mining of salt-tolerant genes in halophyte-Zoysia matrella through cDNA expression library screening.

    PubMed

    Chen, Yu; Zong, Junqin; Tan, Zhiqun; Li, Lanlan; Hu, Baoyun; Chen, Chuanming; Chen, Jingbo; Liu, Jianxiu

    2015-04-01

    Though a large number of salt-tolerant genes were identified from Glycophyte in previous study, genes involved in salt-tolerance of halophyte were scarcely studied. In this report, an important halophyte turfgrass, Zoysia matrella, was used for systematic excavation of salt-tolerant genes using full-length cDNA expression library in yeast. Adopting the Gateway-compatible vector system, a high quality entry library was constructed, containing 3 × 10(6) clones with an average inserted fragments length of 1.64 kb representing a 100% full-length rate. The yeast expression library was screened in a salt-sensitive yeast mutant. The screening yielded dozens of salt-tolerant clones harboring 16 candidate salt-tolerant genes. Under salt-stress condition, these 16 genes exhibited different transcription levels. According to the results, we concluded that the salt-tolerance of Z. matrella might result from known genes involved in ion regulation, osmotic adjustment, as well as unknown pathway associated with protein folding and modification, RNA metabolism, and mitochondrial membrane translocase, etc. In addition, these results shall provide new insight for the future researches with respect to salt-tolerance.

  13. Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids

    PubMed Central

    L'Espérance, Sylvain; Bachvarova, Magdalena; Tetu, Bernard; Mes-Masson, Anne-Marie; Bachvarov, Dimcho

    2008-01-01

    Background Chemotherapy (CT) resistance in ovarian cancer (OC) is broad and encompasses diverse unrelated drugs, suggesting more than one mechanism of resistance. To better understand the molecular mechanisms controlling the immediate response of OC cells to CT exposure, we have performed gene expression profiling in spheroid cultures derived from six OC cell lines (OVCAR3, SKOV3, TOV-112, TOV-21, OV-90 and TOV-155), following treatment with 10,0 μM cisplatin, 2,5 μM paclitaxel or 5,0 μM topotecan for 72 hours. Results Exposure of OC spheroids to these CT drugs resulted in differential expression of genes associated with cell growth and proliferation, cellular assembly and organization, cell death, cell cycle control and cell signaling. Genes, functionally involved in DNA repair, DNA replication and cell cycle arrest were mostly overexpressed, while genes implicated in metabolism (especially lipid metabolism), signal transduction, immune and inflammatory response, transport, transcription regulation and protein biosynthesis, were commonly suppressed following all treatments. Cisplatin and topotecan treatments triggered similar alterations in gene and pathway expression patterns, while paclitaxel action was mainly associated with induction of genes and pathways linked to cellular assembly and organization (including numerous tubulin genes), cell death and protein synthesis. The microarray data were further confirmed by pathway and network analyses. Conclusion Most alterations in gene expression were directly related to mechanisms of the cytotoxics actions in OC spheroids. However, the induction of genes linked to mechanisms of DNA replication and repair in cisplatin- and topotecan-treated OC spheroids could be associated with immediate adaptive response to treatment. Similarly, overexpression of different tubulin genes upon exposure to paclitaxel could represent an early compensatory effect to this drug action. Finally, multicellular growth conditions that are

  14. Global Metabolic Reconstruction and Metabolic Gene Evolution in the Cattle Genome

    PubMed Central

    Kim, Woonsu; Park, Hyesun; Seo, Seongwon

    2016-01-01

    The sequence of cattle genome provided a valuable opportunity to systematically link genetic and metabolic traits of cattle. The objectives of this study were 1) to reconstruct genome-scale cattle-specific metabolic pathways based on the most recent and updated cattle genome build and 2) to identify duplicated metabolic genes in the cattle genome for better understanding of metabolic adaptations in cattle. A bioinformatic pipeline of an organism for amalgamating genomic annotations from multiple sources was updated. Using this, an amalgamated cattle genome database based on UMD_3.1, was created. The amalgamated cattle genome database is composed of a total of 33,292 genes: 19,123 consensus genes between NCBI and Ensembl databases, 8,410 and 5,493 genes only found in NCBI or Ensembl, respectively, and 266 genes from NCBI scaffolds. A metabolic reconstruction of the cattle genome and cattle pathway genome database (PGDB) was also developed using Pathway Tools, followed by an intensive manual curation. The manual curation filled or revised 68 pathway holes, deleted 36 metabolic pathways, and added 23 metabolic pathways. Consequently, the curated cattle PGDB contains 304 metabolic pathways, 2,460 reactions including 2,371 enzymatic reactions, and 4,012 enzymes. Furthermore, this study identified eight duplicated genes in 12 metabolic pathways in the cattle genome compared to human and mouse. Some of these duplicated genes are related with specific hormone biosynthesis and detoxifications. The updated genome-scale metabolic reconstruction is a useful tool for understanding biology and metabolic characteristics in cattle. There has been significant improvements in the quality of cattle genome annotations and the MetaCyc database. The duplicated metabolic genes in the cattle genome compared to human and mouse implies evolutionary changes in the cattle genome and provides a useful information for further research on understanding metabolic adaptations of cattle. PMID

  15. Global Metabolic Reconstruction and Metabolic Gene Evolution in the Cattle Genome.

    PubMed

    Kim, Woonsu; Park, Hyesun; Seo, Seongwon

    2016-01-01

    The sequence of cattle genome provided a valuable opportunity to systematically link genetic and metabolic traits of cattle. The objectives of this study were 1) to reconstruct genome-scale cattle-specific metabolic pathways based on the most recent and updated cattle genome build and 2) to identify duplicated metabolic genes in the cattle genome for better understanding of metabolic adaptations in cattle. A bioinformatic pipeline of an organism for amalgamating genomic annotations from multiple sources was updated. Using this, an amalgamated cattle genome database based on UMD_3.1, was created. The amalgamated cattle genome database is composed of a total of 33,292 genes: 19,123 consensus genes between NCBI and Ensembl databases, 8,410 and 5,493 genes only found in NCBI or Ensembl, respectively, and 266 genes from NCBI scaffolds. A metabolic reconstruction of the cattle genome and cattle pathway genome database (PGDB) was also developed using Pathway Tools, followed by an intensive manual curation. The manual curation filled or revised 68 pathway holes, deleted 36 metabolic pathways, and added 23 metabolic pathways. Consequently, the curated cattle PGDB contains 304 metabolic pathways, 2,460 reactions including 2,371 enzymatic reactions, and 4,012 enzymes. Furthermore, this study identified eight duplicated genes in 12 metabolic pathways in the cattle genome compared to human and mouse. Some of these duplicated genes are related with specific hormone biosynthesis and detoxifications. The updated genome-scale metabolic reconstruction is a useful tool for understanding biology and metabolic characteristics in cattle. There has been significant improvements in the quality of cattle genome annotations and the MetaCyc database. The duplicated metabolic genes in the cattle genome compared to human and mouse implies evolutionary changes in the cattle genome and provides a useful information for further research on understanding metabolic adaptations of cattle.

  16. Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia

    PubMed Central

    Cui, Xiaohui; Bi, Yingtao; Davuluri, Ramana; Xiao, Ying-Yi; Wilson, Michael; Owens, Kristina; Zhang, Yi; Perkins, Archibald

    2013-01-01

    The ecotropic virus integration site 1 (EVI1) transcription factor is associated with human myeloid malignancy of poor prognosis and is overexpressed in 8–10% of adult AML and strikingly up to 27% of pediatric MLL-rearranged leukemias. For the first time, we report comprehensive genomewide EVI1 binding and whole transcriptome gene deregulation in leukemic cells using a combination of ChIP-Seq and RNA-Seq expression profiling. We found disruption of terminal myeloid differentiation and cell cycle regulation to be prominent in EVI-induced leukemogenesis. Specifically, we identified EVI1 directly binds to and downregulates the master myeloid differentiation gene Cebpe and several of its downstream gene targets critical for terminal myeloid differentiation. We also found EVI1 binds to and downregulates Serpinb2 as well as numerous genes involved in the Jak-Stat signaling pathway. Finally, we identified decreased expression of several ATP-dependent P2X purinoreceptors genes involved in apoptosis mechanisms. These findings provide a foundation for future study of potential therapeutic gene targets for EVI1-induced leukemia. PMID:23826213

  17. Changes in global gene expression during in vitro decidualization of rat endometrial stromal cells

    PubMed Central

    Vallejo, Griselda; Maschi, Darío; Citrinovitz, Ana Cecilia Mestre; Aiba, Kazuhiro; Maronna, Ricardo; Yohai, Victor; Ko, Minoru S. H.; Beato, Miguel; Saragüeta, Patricia

    2009-01-01

    During the preimplantation phase of pregnancy the endometrial stroma differentiates into decidua, a process that implies numerous morphological changes and is an example of physiological transdifferentiation. Here we show that UIII rat endometrial stromal cells cultured in the presence of calf serum acquired morphological features of decidual cells and expressed decidual markers. To identify genes involved in decidualization we compared gene expression patterns of control and decidualized UIII cells using cDNA microarray. We found 322 annotated genes exhibiting significant differences in expression (>3 fold, FDR > 0.005), of which 312 have not been previously related to decidualization. Analysis of overrepresented functions revealed that protein synthesis, gene expression and chromatin architecture and remodeling are the most relevant modified functions during decidualization. Relevant genes are also found in the functional terms differentiation, cell proliferation, signal transduction, and matrix/structural proteins. Several of these new genes involved in decidualization (Csdc2, Trim27, Eef1a1, Bmp1, Wt1, Aes, Gna12, and Men1) are shown to be also regulated in uterine decidua during normal pregnancy. Thus, the UIII cell culture model will allow future mechanistic studies to define the transcriptional network regulating reprogramming of stromal cells into decidual cells. PMID:19780023

  18. Global regulation of gene expression by OxyR in an important human opportunistic pathogen

    PubMed Central

    Wei, Qing; Le Minh, Phu Nguyen; Dötsch, Andreas; Hildebrand, Falk; Panmanee, Warunya; Elfarash, Ameer; Schulz, Sebastian; Plaisance, Stéphane; Charlier, Daniel; Hassett, Daniel; Häussler, Susanne; Cornelis, Pierre

    2012-01-01

    Most bacteria control oxidative stress through the H2O2-responsive transactivator OxyR, a member of the LTTR family (LysR Type Transcriptional Regulators), which activates the expression of defensive genes such as those encoding catalases, alkyl hydroperoxide reductases and superoxide dismutases. In the human opportunistic pathogen Pseudomonas aeruginosa, OxyR positively regulates expression of the oxidative stress response genes katA, katB, ahpB and ahpCF. To identify additional targets of OxyR in P. aeruginosa PAO1, we performed chromatin immunoprecipitation in combination with whole genome tiling array analyses (ChIP-chip). We detected 56 genes including all the previously identified defensive genes and a battery of novel direct targets of OxyR. Electrophoretic mobility shift assays (EMSAs) for selected newly identified targets indicated that ∼70% of those were bound by purified oxidized OxyR and their regulation was confirmed by quantitative real-time polymerase chain reaction. Furthermore, a thioredoxin system was identified to enzymatically reduce OxyR under oxidative stress. Functional classification analysis showed that OxyR controls a core regulon of oxidative stress defensive genes, and other genes involved in regulation of iron homeostasis (pvdS), quorum-sensing (rsaL), protein synthesis (rpsL) and oxidative phosphorylation (cyoA and snr1). Collectively, our results indicate that OxyR is involved in oxidative stress defense and regulates other aspects of cellular metabolism as well. PMID:22275523

  19. Global genomic and transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism

    PubMed Central

    Fadista, João; Vikman, Petter; Laakso, Emilia Ottosson; Mollet, Inês Guerra; Esguerra, Jonathan Lou; Taneera, Jalal; Storm, Petter; Osmark, Peter; Ladenvall, Claes; Prasad, Rashmi B.; Hansson, Karin B.; Finotello, Francesca; Uvebrant, Kristina; Ofori, Jones K.; Di Camillo, Barbara; Krus, Ulrika; Cilio, Corrado M.; Hansson, Ola; Eliasson, Lena; Rosengren, Anders H.; Renström, Erik; Wollheim, Claes B.; Groop, Leif

    2014-01-01

    Genetic variation can modulate gene expression, and thereby phenotypic variation and susceptibility to complex diseases such as type 2 diabetes (T2D). Here we harnessed the potential of DNA and RNA sequencing in human pancreatic islets from 89 deceased donors to identify genes of potential importance in the pathogenesis of T2D. We present a catalog of genetic variants regulating gene expression (eQTL) and exon use (sQTL), including many long noncoding RNAs, which are enriched in known T2D-associated loci. Of 35 eQTL genes, whose expression differed between normoglycemic and hyperglycemic individuals, siRNA of tetraspanin 33 (TSPAN33), 5′-nucleotidase, ecto (NT5E), transmembrane emp24 protein transport domain containing 6 (TMED6), and p21 protein activated kinase 7 (PAK7) in INS1 cells resulted in reduced glucose-stimulated insulin secretion. In addition, we provide a genome-wide catalog of allelic expression imbalance, which is also enriched in known T2D-associated loci. Notably, allelic imbalance in paternally expressed gene 3 (PEG3) was associated with its promoter methylation and T2D status. Finally, RNA editing events were less common in islets than previously suggested in other tissues. Taken together, this study provides new insights into the complexity of gene regulation in human pancreatic islets and better understanding of how genetic variation can influence glucose metabolism. PMID:25201977

  20. Global genomic and transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism.

    PubMed

    Fadista, João; Vikman, Petter; Laakso, Emilia Ottosson; Mollet, Inês Guerra; Esguerra, Jonathan Lou; Taneera, Jalal; Storm, Petter; Osmark, Peter; Ladenvall, Claes; Prasad, Rashmi B; Hansson, Karin B; Finotello, Francesca; Uvebrant, Kristina; Ofori, Jones K; Di Camillo, Barbara; Krus, Ulrika; Cilio, Corrado M; Hansson, Ola; Eliasson, Lena; Rosengren, Anders H; Renström, Erik; Wollheim, Claes B; Groop, Leif

    2014-09-23

    Genetic variation can modulate gene expression, and thereby phenotypic variation and susceptibility to complex diseases such as type 2 diabetes (T2D). Here we harnessed the potential of DNA and RNA sequencing in human pancreatic islets from 89 deceased donors to identify genes of potential importance in the pathogenesis of T2D. We present a catalog of genetic variants regulating gene expression (eQTL) and exon use (sQTL), including many long noncoding RNAs, which are enriched in known T2D-associated loci. Of 35 eQTL genes, whose expression differed between normoglycemic and hyperglycemic individuals, siRNA of tetraspanin 33 (TSPAN33), 5'-nucleotidase, ecto (NT5E), transmembrane emp24 protein transport domain containing 6 (TMED6), and p21 protein activated kinase 7 (PAK7) in INS1 cells resulted in reduced glucose-stimulated insulin secretion. In addition, we provide a genome-wide catalog of allelic expression imbalance, which is also enriched in known T2D-associated loci. Notably, allelic imbalance in paternally expressed gene 3 (PEG3) was associated with its promoter methylation and T2D status. Finally, RNA editing events were less common in islets than previously suggested in other tissues. Taken together, this study provides new insights into the complexity of gene regulation in human pancreatic islets and better understanding of how genetic variation can influence glucose metabolism.

  1. The metabolic background is a global player in Saccharomyces gene expression epistasis.

    PubMed

    Alam, Mohammad Tauqeer; Zelezniak, Aleksej; Mülleder, Michael; Shliaha, Pavel; Schwarz, Roland; Capuano, Floriana; Vowinckel, Jakob; Radmaneshfar, Elahe; Krüger, Antje; Calvani, Enrica; Michel, Steve; Börno, Stefan; Christen, Stefan; Patil, Kiran Raosaheb; Timmermann, Bernd; Lilley, Kathryn S; Ralser, Markus

    2016-01-01

    The regulation of gene expression in response to nutrient availability is fundamental to the genotype-phenotype relationship. The metabolic-genetic make-up of the cell, as reflected in auxotrophy, is hence likely to be a determinant of gene expression. Here, we address the importance of the metabolic-genetic background by monitoring transcriptome, proteome and metabolome in a repertoire of 16 Saccharomyces cerevisiae laboratory backgrounds, combinatorially perturbed in histidine, leucine, methionine and uracil biosynthesis. The metabolic background affected up to 85% of the coding genome. Suggesting widespread confounding, these transcriptional changes show, on average, 83% overlap between unrelated auxotrophs and 35% with previously published transcriptomes generated for non-metabolic gene knockouts. Background-dependent gene expression correlated with metabolic flux and acted, predominantly through masking or suppression, on 88% of transcriptional interactions epistatically. As a consequence, the deletion of the same metabolic gene in a different background could provoke an entirely different transcriptional response. Propagating to the proteome and scaling up at the metabolome, metabolic background dependencies reveal the prevalence of metabolism-dependent epistasis at all regulatory levels. Urging a fundamental change of the prevailing laboratory practice of using auxotrophs and nutrient supplemented media, these results reveal epistatic intertwining of metabolism with gene expression on the genomic scale. PMID:27572163

  2. Mining genes involved in the stratification of Paris Polyphylla seeds using high-throughput embryo Transcriptome sequencing

    PubMed Central

    2013-01-01

    Background Paris polyphylla var. yunnanensis is an important medicinal plant. Seed dormancy is one of the main factors restricting artificial cultivation. The molecular mechanisms of seed dormancy remain unclear, and little genomic or transcriptome data are available for this plant. Results In this study, massive parallel pyrosequencing on the Roche 454-GS FLX Titanium platform was used to generate a substantial sequence dataset for the P. polyphylla embryo. 369,496 high quality reads were obtained, ranging from 50 to 1146 bp, with a mean of 219 bp. These reads were assembled into 47,768 unigenes, which included 16,069 contigs and 31,699 singletons. Using BLASTX searches of public databases, 15,757 (32.3%) unique transcripts were identified. Gene Ontology and Cluster of Orthologous Groups of proteins annotations revealed that these transcripts were broadly representative of the P. polyphylla embryo transcriptome. The Kyoto Encyclopedia of Genes and Genomes assigned 5961 of the unique sequences to specific metabolic pathways. Relative expression levels analysis showed that eleven phytohormone-related genes and five other genes have different expression patterns in the embryo and endosperm in the seed stratification process. Conclusions Gene annotation and quantitative RT-PCR expression analysis identified 464 transcripts that may be involved in phytohormone catabolism and biosynthesis, hormone signal, seed dormancy, seed maturation, cell wall growth and circadian rhythms. In particular, the relative expression analysis of sixteen genes (CYP707A, NCED, GA20ox2, GA20ox3, ABI2, PP2C, ARP3, ARP7, IAAH, IAAS, BRRK, DRM, ELF1, ELF2, SFR6, and SUS) in embryo and endosperm and at two temperatures indicated that these related genes may be candidates for clarifying the molecular basis of seed dormancy in P. polyphlla var. yunnanensis. PMID:23718911

  3. Abundance and activity of 16S rRNA, amoA and nifH bacterial genes during assisted phytostabilization of mine tailings

    PubMed Central

    Nelson, Karis N.; Neilson, Julia W.; Root, Robert A.; Chorover, Jon; Maier, Raina M.

    2014-01-01

    Mine tailings in semiarid regions are highly susceptible to erosion and are sources of dust pollution and potential avenues of human exposure to toxic metals. One constraint to revegetation of tailings by phytostabilization is the absence of microbial communities critical for biogeochemical cycling of plant nutrients. The objective of this study was to evaluate specific genes as in situ indicators of biological soil response during phytoremediation. The abundance and activity of 16S rRNA, nifH, and amoA were monitored during a nine month phytostabilization study using buffalo grass and quailbush grown in compost-amended, metalliferous tailings. The compost amendment provided a greater than 5-log increase in bacterial abundance, and survival of this compost-inoculum was more stable in planted treatments. Despite increased abundance, the activity of the introduced community was low, and significant increases were not detected until six and nine months in quailbush, and unplanted compost and buffalo grass treatments, respectively. In addition, increased abundances of nitrogen-fixation (nifH) and ammonia-oxidizing (amoA) genes were observed in rhizospheres of buffalo grass and quailbush, respectively. Thus, plant establishment facilitated the short term stabilization of introduced bacterial biomass and supported the growth of two key nitrogen-cycling populations in compost-amended tailings. PMID:25495940

  4. PolySearch2: a significantly improved text-mining system for discovering associations between human diseases, genes, drugs, metabolites, toxins and more.

    PubMed

    Liu, Yifeng; Liang, Yongjie; Wishart, David

    2015-07-01

    PolySearch2 (http://polysearch.ca) is an online text-mining system for identifying relationships between biomedical entities such as human diseases, genes, SNPs, proteins, drugs, metabolites, toxins, metabolic pathways, organs, tissues, subcellular organelles, positive health effects, negative health effects, drug actions, Gene Ontology terms, MeSH terms, ICD-10 medical codes, biological taxonomies and chemical taxonomies. PolySearch2 supports a generalized 'Given X, find all associated Ys' query, where X and Y can be selected from the aforementioned biomedical entities. An example query might be: 'Find all diseases associated with Bisphenol A'. To find its answers, PolySearch2 searches for associations against comprehensive collections of free-text collections, including local versions of MEDLINE abstracts, PubMed Central full-text articles, Wikipedia full-text articles and US Patent application abstracts. PolySearch2 also searches 14 widely used, text-rich biological databases such as UniProt, DrugBank and Human Metabolome Database to improve its accuracy and coverage. PolySearch2 maintains an extensive thesaurus of biological terms and exploits the latest search engine technology to rapidly retrieve relevant articles and databases records. PolySearch2 also generates, ranks and annotates associative candidates and present results with relevancy statistics and highlighted key sentences to facilitate user interpretation.

  5. PolySearch2: a significantly improved text-mining system for discovering associations between human diseases, genes, drugs, metabolites, toxins and more

    PubMed Central

    Liu, Yifeng; Liang, Yongjie; Wishart, David

    2015-01-01

    PolySearch2 (http://polysearch.ca) is an online text-mining system for identifying relationships between biomedical entities such as human diseases, genes, SNPs, proteins, drugs, metabolites, toxins, metabolic pathways, organs, tissues, subcellular organelles, positive health effects, negative health effects, drug actions, Gene Ontology terms, MeSH terms, ICD-10 medical codes, biological taxonomies and chemical taxonomies. PolySearch2 supports a generalized ‘Given X, find all associated Ys’ query, where X and Y can be selected from the aforementioned biomedical entities. An example query might be: ‘Find all diseases associated with Bisphenol A’. To find its answers, PolySearch2 searches for associations against comprehensive collections of free-text collections, including local versions of MEDLINE abstracts, PubMed Central full-text articles, Wikipedia full-text articles and US Patent application abstracts. PolySearch2 also searches 14 widely used, text-rich biological databases such as UniProt, DrugBank and Human Metabolome Database to improve its accuracy and coverage. PolySearch2 maintains an extensive thesaurus of biological terms and exploits the latest search engine technology to rapidly retrieve relevant articles and databases records. PolySearch2 also generates, ranks and annotates associative candidates and present results with relevancy statistics and highlighted key sentences to facilitate user interpretation. PMID:25925572

  6. PolySearch2: a significantly improved text-mining system for discovering associations between human diseases, genes, drugs, metabolites, toxins and more.

    PubMed

    Liu, Yifeng; Liang, Yongjie; Wishart, David

    2015-07-01

    PolySearch2 (http://polysearch.ca) is an online text-mining system for identifying relationships between biomedical entities such as human diseases, genes, SNPs, proteins, drugs, metabolites, toxins, metabolic pathways, organs, tissues, subcellular organelles, positive health effects, negative health effects, drug actions, Gene Ontology terms, MeSH terms, ICD-10 medical codes, biological taxonomies and chemical taxonomies. PolySearch2 supports a generalized 'Given X, find all associated Ys' query, where X and Y can be selected from the aforementioned biomedical entities. An example query might be: 'Find all diseases associated with Bisphenol A'. To find its answers, PolySearch2 searches for associations against comprehensive collections of free-text collections, including local versions of MEDLINE abstracts, PubMed Central full-text articles, Wikipedia full-text articles and US Patent application abstracts. PolySearch2 also searches 14 widely used, text-rich biological databases such as UniProt, DrugBank and Human Metabolome Database to improve its accuracy and coverage. PolySearch2 maintains an extensive thesaurus of biological terms and exploits the latest search engine technology to rapidly retrieve relevant articles and databases records. PolySearch2 also generates, ranks and annotates associative candidates and present results with relevancy statistics and highlighted key sentences to facilitate user interpretation. PMID:25925572

  7. Abundance and Activity of 16S rRNA, AmoA and NifH Bacterial Genes During Assisted Phytostabilization of Mine Tailings.

    PubMed

    Nelson, Karis N; Neilson, Julia W; Root, Robert A; Chorover, Jon; Maier, Raina M

    2015-01-01

    Mine tailings in semiarid regions are highly susceptible to erosion and are sources of dust pollution and potential avenues of human exposure to toxic metals. One constraint to revegetation of tailings by phytostabilization is the absence of microbial communities critical for biogeochemical cycling of plant nutrients. The objective of this study was to evaluate specific genes as in situ indicators of biological soil response during phytoremediation. The abundance and activity of 16S rRNA, nifH, and amoA were monitored during a nine month phytostabilization study using buffalo grass and quailbush grown in compost-amended, metalliferous tailings. The compost amendment provided a greater than 5-log increase in bacterial abundance, and survival of this compost-inoculum was more stable in planted treatments. Despite increased abundance, the activity of the introduced community was low, and significant increases were not detected until six and nine months in quailbush, and unplanted compost and buffalo grass treatments, respectively. In addition, increased abundances of nitrogen-fixation (nifH) and ammonia-oxidizing (amoA) genes were observed in rhizospheres of buffalo grass and quailbush, respectively. Thus, plant establishment facilitated the short term stabilization of introduced bacterial biomass and supported the growth of two key nitrogen-cycling populations in compost-amended tailings. PMID:25495940

  8. Abundance and Activity of 16S rRNA, AmoA and NifH Bacterial Genes During Assisted Phytostabilization of Mine Tailings.

    PubMed

    Nelson, Karis N; Neilson, Julia W; Root, Robert A; Chorover, Jon; Maier, Raina M

    2015-01-01

    Mine tailings in semiarid regions are highly susceptible to erosion and are sources of dust pollution and potential avenues of human exposure to toxic metals. One constraint to revegetation of tailings by phytostabilization is the absence of microbial communities critical for biogeochemical cycling of plant nutrients. The objective of this study was to evaluate specific genes as in situ indicators of biological soil response during phytoremediation. The abundance and activity of 16S rRNA, nifH, and amoA were monitored during a nine month phytostabilization study using buffalo grass and quailbush grown in compost-amended, metalliferous tailings. The compost amendment provided a greater than 5-log increase in bacterial abundance, and survival of this compost-inoculum was more stable in planted treatments. Despite increased abundance, the activity of the introduced community was low, and significant increases were not detected until six and nine months in quailbush, and unplanted compost and buffalo grass treatments, respectively. In addition, increased abundances of nitrogen-fixation (nifH) and ammonia-oxidizing (amoA) genes were observed in rhizospheres of buffalo grass and quailbush, respectively. Thus, plant establishment facilitated the short term stabilization of introduced bacterial biomass and supported the growth of two key nitrogen-cycling populations in compost-amended tailings.

  9. Global Gene Expression Responses to Low- or High-Dose Radiation in a Human Three-Dimensional Tissue Model

    PubMed Central

    Mezentsev, Alexandre; Amundson, Sally A.

    2011-01-01

    Accumulating data suggest that the biological responses to high and low doses of radiation are qualitatively different, necessitating the direct study of low-dose responses to better understand potential risks. Most such studies have used two-dimensional culture systems, which may not fully represent responses in three-dimensional tissues. To gain insight into low-dose responses in tissue, we have profiled global gene expression in EPI-200, a three-dimensional tissue model that imitates the structure and function of human epidermis, at 4, 16 and 24 h after exposure to high (2.5 Gy) and low (0.1 Gy) doses of low-LET protons. The most significant gene ontology groups among genes altered in expression were consistent with effects observed at the tissue level, where the low dose was associated with recovery and tissue repair, while the high dose resulted in loss of structural integrity and terminal differentiation. Network analysis of the significantly responding genes suggested that TP53 dominated the response to 2.5 Gy, while HNF4A, a novel transcription factor not previously associated with radiation response, was most prominent in the low-dose response. HNF4A protein levels and phosphorylation were found to increase in tissues and cells after low- but not high-dose irradiation. PMID:21486161

  10. Analyzing the miRNA-Gene Networks to Mine the Important miRNAs under Skin of Human and Mouse

    PubMed Central

    Gong, Husile

    2016-01-01

    Genetic networks provide new mechanistic insights into the diversity of species morphology. In this study, we have integrated the MGI, GEO, and miRNA database to analyze the genetic regulatory networks under morphology difference of integument of humans and mice. We found that the gene expression network in the skin is highly divergent between human and mouse. The GO term of secretion was highly enriched, and this category was specific in human compared to mouse. These secretion genes might be involved in eccrine system evolution in human. In addition, total 62,637 miRNA binding target sites were predicted in human integument genes (IGs), while 26,280 miRNA binding target sites were predicted in mouse IGs. The interactions between miRNAs and IGs in human are more complex than those in mouse. Furthermore, hsa-miR-548, mmu-miR-466, and mmu-miR-467 have an enormous number of targets on IGs, which both have the role of inhibition of host immunity response. The pattern of distribution on the chromosome of these three miRNAs families is very different. The interaction of miRNA/IGs has added the new dimension in traditional gene regulation networks of skin. Our results are generating new insights into the gene networks basis of skin difference between human and mouse.

  11. Single nucleotide polymorphism mining and nucleotide sequence analysis of Mx1 gene in exonic regions of Japanese quail

    PubMed Central

    Niraj, Diwesh Kumar; Kumar, Pushpendra; Mishra, Chinmoy; Narayan, Raj; Bhattacharya, Tarun Kumar; Shrivastava, Kush; Bhushan, Bharat; Tiwari, Ashok Kumar; Saxena, Vishesh; Sahoo, Nihar Ranjan; Sharma, Deepak

    2015-01-01

    Aim: An attempt has been made to study the Myxovirus resistant (Mx1) gene polymorphism in Japanese quail. Materials and Methods: In the present, investigation four fragments viz. Fragment I of 185 bp (Exon 3 region), Fragment II of 148 bp (Exon 5 region), Fragment III of 161 bp (Exon 7 region), and Fragment IV of 176 bp (Exon 13 region) of Mx1 gene were amplified and screened for polymorphism by polymerase chain reaction-single-strand conformation polymorphism technique in 170 Japanese quail birds. Results: Out of the four fragments, one fragment (Fragment II) was found to be polymorphic. Remaining three fragments (Fragment I, III, and IV) were found to be monomorphic which was confirmed by custom sequencing. Overall nucleotide sequence analysis of Mx1 gene of Japanese quail showed 100% homology with common quail and more than 80% homology with reported sequence of chicken breeds. Conclusion: The Mx1 gene is mostly conserved in Japanese quail. There is an urgent need of comprehensive analysis of other regions of Mx1 gene along with its possible association with the traits of economic importance in Japanese quail. PMID:27047057

  12. Analyzing the miRNA-Gene Networks to Mine the Important miRNAs under Skin of Human and Mouse

    PubMed Central

    Gong, Husile

    2016-01-01

    Genetic networks provide new mechanistic insights into the diversity of species morphology. In this study, we have integrated the MGI, GEO, and miRNA database to analyze the genetic regulatory networks under morphology difference of integument of humans and mice. We found that the gene expression network in the skin is highly divergent between human and mouse. The GO term of secretion was highly enriched, and this category was specific in human compared to mouse. These secretion genes might be involved in eccrine system evolution in human. In addition, total 62,637 miRNA binding target sites were predicted in human integument genes (IGs), while 26,280 miRNA binding target sites were predicted in mouse IGs. The interactions between miRNAs and IGs in human are more complex than those in mouse. Furthermore, hsa-miR-548, mmu-miR-466, and mmu-miR-467 have an enormous number of targets on IGs, which both have the role of inhibition of host immunity response. The pattern of distribution on the chromosome of these three miRNAs families is very different. The interaction of miRNA/IGs has added the new dimension in traditional gene regulation networks of skin. Our results are generating new insights into the gene networks basis of skin difference between human and mouse. PMID:27689084

  13. Global Analysis of Differentially Expressed Genes and Proteins in the Wheat Callus Infected by Agrobacterium tumefaciens

    PubMed Central

    Zhou, Xiaohong; Wang, Ke; Lv, Dongwen; Wu, Chengjun; Li, Jiarui; Zhao, Pei; Lin, Zhishan; Du, Lipu; Yan, Yueming; Ye, Xingguo

    2013-01-01

    Agrobacterium-mediated plant transformation is an extremely complex and evolved process involving genetic determinants of both the bacteria and the host plant cells. However, the mechanism of the determinants remains obscure, especially in some cereal crops such as wheat, which is recalcitrant for Agrobacterium-mediated transformation. In this study, differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were analyzed in wheat callus cells co-cultured with Agrobacterium by using RNA sequencing (RNA-seq) and two-dimensional electrophoresis (2-DE) in conjunction with mass spectrometry (MS). A set of 4,889 DEGs and 90 DEPs were identified, respectively. Most of them are related to metabolism, chromatin assembly or disassembly and immune defense. After comparative analysis, 24 of the 90 DEPs were detected in RNA-seq and proteomics datasets simultaneously. In addition, real-time RT-PCR experiments were performed to check the differential expression of the 24 genes, and the results were consistent with the RNA-seq data. According to gene ontology (GO) analysis, we found that a big part of these differentially expressed genes were related to the process of stress or immunity response. Several putative determinants and candidate effectors responsive to Agrobacterium mediated transformation of wheat cells were discussed. We speculate that some of these genes are possibly related to Agrobacterium infection. Our results will help to understand the interaction between Agrobacterium and host cells, and may facilitate developing efficient transformation strategies in cereal crops. PMID:24278131

  14. Prospective Study of Metal Fume-Induced Responses of Global Gene Expression Profiling in Whole Blood

    PubMed Central

    Wang, Zhaoxi; Neuberg, Donna; Su, Li; Kim, Jee Young; Chen, Jiu-Chiuan; Christiani, David C.

    2008-01-01

    Metal particulate inhalation causes pulmonary and cardiovascular diseases. Our previous results showed that systemic responses to short-term occupational welding-fume exposure could be assessed by microarray analyses in whole-blood total RNA sampled before and after exposure. To expand our understanding of the duration of particulate-induced gene expression changes, we conducted a study using a similar population 1 yr after the original study and extended our observations in the postexposure period. We recruited 15 individuals with welding fume exposure and 7 nonexposed individuals. Thirteen of the 22 individuals (9 in exposed group and 4 in nonexposed group) had been monitored in the previous study. Whole-blood total RNA was analyzed at 3 time points, including baseline, immediately following exposure (approximately 5 h after baseline), and 24 h after baseline, using cDNA microarray technology. We replicated the patterns of Gene Ontology (GO) terms associated with response to stimulus, cell death, phosphorus metabolism, localization, and regulation of biological processes significantly enriched with altered genes in the nonsmoking exposed group. Most of the identified genes had opposite expression changes between the exposure and postexposure periods in nonsmoking welders. In addition, we found dose-dependent patterns that were affected by smoking status. In conclusion, short-term occupational exposure to metal particulates causes systemic responses in the peripheral blood. Furthermore, the acute particulate-induced effects on gene expression profiling were transient in nonsmoking welders, with most effects diminishing within 19 h following exposure. PMID:18951227

  15. Ldb1-nucleated transcription complexes function as primary mediators of global erythroid gene activation

    PubMed Central

    Li, LiQi; Freudenberg, Johannes; Cui, Kairong; Dale, Ryan; Song, Sang-Hyun; Dean, Ann; Zhao, Keji

    2013-01-01

    Erythropoiesis is dependent on the lineage-specific transcription factors Gata1, Tal1, and Klf1. Several erythroid genes have been shown to require all 3 factors for their expression, suggesting that they function synergistically; however, there is little direct evidence for widespread cooperation. Gata1 and Tal1 can assemble within higher-order protein complexes (Ldb1 complexes) that include the adapter molecules Lmo2 and Ldb1. Ldb1 proteins are capable of coassociation, and long-range Ldb1-mediated oligomerization of enhancer- and promoter-bound Ldb1 complexes has been shown to be required for β-globin gene expression. In this study, we generated a genomewide map of Ldb1 complex binding sites that revealed widespread binding at erythroid genes and at known erythroid enhancer elements. Ldb1 complex binding sites frequently colocalized with Klf1 binding sites and with consensus binding motifs for other erythroid transcription factors. Transcriptomic analysis demonstrated a strong correlation between Ldb1 complex binding and Ldb1 dependency for gene expression and identified a large cohort of genes coregulated by Ldb1 complexes and Klf1. Together, these results provide a foundation for defining the mechanism and scope of Ldb1 complex activity during erythropoiesis. PMID:23610375

  16. Mining of Novel Thermo-Stable Cellulolytic Genes from a Thermophilic Cellulose-Degrading Consortium by Metagenomics

    PubMed Central

    Xia, Yu; Ju, Feng; Fang, Herbert H. P.; Zhang, Tong

    2013-01-01

    In this study, metagenomics was applied to characterize the microbial community and to discover carbohydrate-active genes of an enriched thermophilic cellulose-degrading sludge. The 16S analysis showed that the sludge microbiome was dominated by genus of cellulolytic Clostridium and methanogenesis Methanothermobacter. In order to retrieve genes from the metagenome, de novo assembly of the 11,930,760 Illumina 100 bp paired-end reads (totally 1.2 Gb) was carried out. 75% of all reads was utilized in the de novo assembly. 31,499 ORFs (Open Reading Frame) with an average length of 852 bp were predicted from the assembly; and 64% of these ORFs were predicted to present full-length genes. Based on the Hidden Markol Model, 253 of the predicted thermo-stable genes were identified as putatively carbohydrate-active. Among them the relative dominance of GH9 (Glycoside Hydrolase) and corresponding CBM3 (Carbohydrate Binding Module) revealed a cellulosome-based attached metabolism of polysaccharide in the thermophilic sludge. The putative carbohydrate-active genes ranged from 20% to 100% amino acid sequence identity to known proteins in NCBI nr database, with half of them showed less than 50% similarity. In addition, the coverage of the genes (in terms of ORFs) identified in the sludge were developed into three clear trends (112×, 29× and 8×) in which 85% of the high coverage trend (112×) mainly consisted of phylum of Firmicutes while 49.3% of the 29× trend was affiliated to the phylum of Chloroflexi. PMID:23341999

  17. Annotation of gene promoters by integrative data-mining of ChIP-seq Pol-II enrichment data

    PubMed Central

    2010-01-01

    Background Use of alternative gene promoters that drive widespread cell-type, tissue-type or developmental gene regulation in mammalian genomes is a common phenomenon. Chromatin immunoprecipitation methods coupled with DNA microarray (ChIP-chip) or massive parallel sequencing (ChIP-seq) are enabling genome-wide identification of active promoters in different cellular conditions using antibodies against Pol-II. However, these methods produce enrichment not only near the gene promoters but also inside the genes and other genomic regions due to the non-specificity of the antibodies used in ChIP. Further, the use of these methods is limited by their high cost and strong dependence on cellular type and context. Methods We trained and tested different state-of-art ensemble and meta classification methods for identification of Pol-II enriched promoter and Pol-II enriched non-promoter sequences, each of length 500 bp. The classification models were trained and tested on a bench-mark dataset, using a set of 39 different feature variables that are based on chromatin modification signatures and various DNA sequence features. The best performing model was applied on seven published ChIP-seq Pol-II datasets to provide genome wide annotation of mouse gene promoters. Results We present a novel algorithm based on supervised learning methods to discriminate promoter associated Pol-II enrichment from enrichment elsewhere in the genome in ChIP-chip/seq profiles. We accumulated a dataset of 11,773 promoter and 46,167 non-promoter sequences, each of length 500 bp, generated from RNA Pol-II ChIP-seq data of five tissues (Brain, Kidney, Liver, Lung and Spleen). We evaluated the classification models in building the best predictor and found that Bagging and Random Forest based approaches give the best accuracy. We implemented the algorithm on seven different published ChIP-seq datasets to provide a comprehensive set of promoter annotations for both protein-coding and non-coding genes in

  18. Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters

    PubMed Central

    Cimermancic, Peter; Medema, Marnix H.; Claesen, Jan; Kurita, Kenji; Wieland Brown, Laura C.; Mavrommatis, Konstantinos; Pati, Amrita; Godfrey, Paul A.; Koehrsen, Michael; Clardy, Jon; Birren, Bruce W.; Takano, Eriko; Sali, Andrej; Linington, Roger G.; Fischbach, Michael A.

    2014-01-01

    Summary Although biosynthetic gene clusters (BGCs) have been discovered for hundreds of bacterial metabolites, our knowledge of their diversity remains limited. Here, we used a novel algorithm to systematically identify BGCs in the extensive extant microbial sequencing data. Network analysis of the predicted BGCs revealed large gene cluster families, the vast majority uncharacterized. We experimentally characterized the most prominent family, consisting of two subfamilies of hundreds of BGCs distributed throughout the Proteobacteria; their products are aryl polyenes, lipids with an aryl head group conjugated to a polyene tail. We identified a distant relationship to a third subfamily of aryl polyene BGCs, and together the three subfamilies represent the largest known family of biosynthetic gene clusters, with more than 1,000 members. Although these clusters are widely divergent in sequence, their small molecule products are remarkably conserved, indicating for the first time the important roles these compounds play in Gram-negative cell biology. PMID:25036635

  19. Global gene expression profiling in human lung cells exposed to cobalt

    PubMed Central

    Malard, Veronique; Berenguer, Frederic; Prat, Odette; Ruat, Sylvie; Steinmetz, Gerard; Quemeneur, Eric

    2007-01-01

    Background It has been estimated that more than 1 million workers in the United States are exposed to cobalt. Occupational exposure to 59 Co occurs mainly via inhalation and leads to various lung diseases. Cobalt is classified by the IARC as a possible human carcinogen (group 2B). Although there is evidence for in vivo and in vitro toxicity, the mechanisms of cobalt-induced lung toxicity are not fully known. The purpose of this work was to identify potential signatures of acute cobalt exposure using a toxicogenomic approach. Data analysis focused on some cellular processes and protein targets that are thought to be relevant for carcinogenesis, transport and biomarker research. Results A time course transcriptome analysis was performed on A549 human pulmonary cells, leading to the identification of 85 genes which are repressed or induced in response to soluble 59 Co. A group of 29 of these genes, representing the main biological functions, was assessed by quantitative RT-PCR. The expression profiles of six of them were then tested by quantitative RT-PCR in a time-dependent manner and three modulations were confirmed by Western blotting. The 85 modulated genes include potential cobalt carriers (FBXL2, ZNT1, SLC12A5), tumor suppressors or transcription factors (MAZ, DLG1, MYC, AXL) and genes linked to the stress response (UBC, HSPCB, BNIP3L). We also identified nine genes coding for secreted proteins as candidates for biomarker research. Of those, TIMP2 was found to be down-regulated and this modulation was confirmed, in a dose-dependent manner, at protein level in the supernatant of exposed cells. Conclusion Most of these genes have never been described as related to cobalt stress and provide original hypotheses for further study of the effects of this metal ion on human lung epithelial cells. A putative biomarker of cobalt toxicity was identified. PMID:17553155

  20. Global gene expression profile of osteoblast-like cells grown on polyester copolymer scaffolds.

    PubMed

    Idris, Shaza B; Bolstad, Anne Isine; Ibrahim, Salah O; Dånmark, Staffan; Finne-Wistrand, Anna; Albertsson, Ann-Christine; Arvidson, Kristina; Mustafa, Kamal

    2011-11-01

    One of the principal goals in tissue engineering is to produce scaffold materials that will guide cells to differentiate and regenerate functional replacement tissue at the site of injury. Poly(l-lactide-co-1,5-dioxepan-2-one) [Poly(LLA-co-DXO)], a potential scaffolding material for bone tissue engineering, has high hydrophilicity. Previous in vitro studies using human osteoblast-like cells (HOBs) demonstrated greater cytocompatibility and enhanced osteogenic differentiation when HOBs were seeded onto Poly(LLA-co-DXO) compared to Poly(l-lactide) [P(LLA)] scaffolds. The aim of the study was to identify the gene expression profiles of HOBs obtained from alveolar bone and grown on Poly(LLA-co-DXO) biodegradable polymer scaffolds compared to P(LLA) one. Illumina HumanWG-6 v3.0 Expression BeadChips were used for the gene expression analysis. Several genes were found as differentially expressed at 24 h and at 21 days. Expression of genes related to cell adhesion, cytoskeleton, antiapoptosis, proliferation, and bone mineralization was influenced by adding the monomer 1,5-dioxepan-2-one to the L-lactide. Genes related to three biological pathways involving Integrin, Notch, and Ras were found to be upregulated. For selected genes, results were confirmed by quantitative reverse transcriptase-polymerase chain reaction. Further, calcium content analysis revealed a significant enhancement of calcium deposition on both tested scaffolds. This observation was confirmed by Von Kossa and Alizarin Red S staining. Findings of this study are relevant to a better understanding of the molecular mechanisms underlying the behavior of HOBs in bone regenerative procedure.

  1. Global Transcriptomic Analysis of Targeted Silencing of Two Paralogous ACC Oxidase Genes in Banana

    PubMed Central

    Xia, Yan; Kuan, Chi; Chiu, Chien-Hsiang; Chen, Xiao-Jing; Do, Yi-Yin; Huang, Pung-Ling

    2016-01-01

    Among 18 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase homologous genes existing in the banana genome there are two genes, Mh-ACO1 and Mh-ACO2, that participate in banana fruit ripening. To better understand the physiological functions of Mh-ACO1 and Mh-ACO2, two hairpin-type siRNA expression vectors targeting both the Mh-ACO1 and Mh-ACO2 were constructed and incorporated into the banana genome by Agrobacterium-mediated transformation. The generation of Mh-ACO1 and Mh-ACO2 RNAi transgenic banana plants was confirmed by Southern blot analysis. To gain insights into the functional diversity and complexity between Mh-ACO1 and Mh-ACO2, transcriptome sequencing of banana fruits using the Illumina next-generation sequencer was performed. A total of 32,093,976 reads, assembled into 88,031 unigenes for 123,617 transcripts were obtained. Significantly enriched Gene Oncology (GO) terms and the number of differentially expressed genes (DEGs) with GO annotation were ‘catalytic activity’ (1327, 56.4%), ‘heme binding’ (65, 2.76%), ‘tetrapyrrole binding’ (66, 2.81%), and ‘oxidoreductase activity’ (287, 12.21%). Real-time RT-PCR was further performed with mRNAs from both peel and pulp of banana fruits in Mh-ACO1 and Mh-ACO2 RNAi transgenic plants. The results showed that expression levels of genes related to ethylene signaling in ripening banana fruits were strongly influenced by the expression of genes associated with ethylene biosynthesis. PMID:27681726

  2. Environmental health consequences of land mines.

    PubMed

    Newman, R D; Mercer, M A

    2000-01-01

    This article reviews the literature on the environmental effects of anti-personnel land mines globally. Land mines represent an immediate environmental health problem. Between 60 and 70 million land mines are currently in place in over 70 countries. Designed to kill or main humans, including civilians, they injure an estimated 1, 200 persons and kill another 800 every week. Land-mine injuries tend to be serious; an estimated 300,000 persons worldwide have been disabled by them. The problem, politically very controversial, can be resolved only by preventing the further placement of mines, by demining of areas already mined, and by coping with the personal and environmental devastation that they have already caused. Environmental health personnel should be involved in promoting awareness of the problem, in improving services for land-mine victims, and in promoting political efforts to ban further use of land mines. PMID:10926729

  3. Identification of new ABA- and MEJA-activated sugarcane bZIP genes by data mining in the SUCEST database.

    PubMed

    Schlögl, Paulo Sérgio; Nogueira, Fábio Tebaldi S; Drummond, Rodrigo; Felix, Juliana M; De Rosa, Vicente E; Vicentini, Renato; Leite, Adilson; Ulian, Eugênio C; Menossi, Marcelo

    2008-02-01

    Sugarcane is generally propagated by cuttings of the stalk containing one or more lateral buds, which will develop into a new plant. The transition from the dormant into the active stage constitutes a complex phenomenon characterized by changes in accumulation of phytohormones and several other physiological aspects. Abscisic acid (ABA) and methyl-jasmonate (MeJA) are major signaling molecules, which influence plant development and stress responses. These plant regulators modulate gene expression with the participation of many transcriptional factors. Basic leucine zipper proteins (bZIPs) form a large family of transcriptional factors involved in a variety of plant physiological processes, such as development and responses to stress. Query sequences consisting of full-length protein sequence of each of the Arabidopsis bZIP families were utilized to screen the sugarcane EST database (SUCEST) and 86 sugarcane assembled sequences (SAS) coding for bZIPs were identified. cDNA arrays and RNA-gel blots were used to study the expression of these sugarcane bZIP genes during early plantlet development and in response to ABA and MeJA. Six bZIP genes were found to be differentially expressed during development. ABA and MeJA modulated the expression of eight sugarcane bZIP genes. Our findings provide novel insights into the expression of this large protein family of transcriptional factors in sugarcane.

  4. Genomic analyses of metal resistance genes in three plant growth promoting bacteria of legume plants in Northwest mine tailings, China.

    PubMed

    Xie, Pin; Hao, Xiuli; Herzberg, Martin; Luo, Yantao; Nies, Dietrich H; Wei, Gehong

    2015-01-01

    To better understand the diversity of metal resistance genetic determinant from microbes that survived at metal tailings in northwest of China, a highly elevated level of heavy metal containing region, genomic analyses was conducted using genome sequence of three native metal-resistant plant growth promoting bacteria (PGPB). It shows that: Mesorhizobium amorphae CCNWGS0123 contains metal transporters from P-type ATPase, CDF (Cation Diffusion Facilitator), HupE/UreJ and CHR (chromate ion transporter) family involved in copper, zinc, nickel as well as chromate resistance and homeostasis. Meanwhile, the putative CopA/CueO system is expected to mediate copper resistance in Sinorhizobium meliloti CCNWSX0020 while ZntA transporter, assisted with putative CzcD, determines zinc tolerance in Agrobacterium tumefaciens CCNWGS0286. The greenhouse experiment provides the consistent evidence of the plant growth promoting effects of these microbes on their hosts by nitrogen fixation and/or indoleacetic acid (IAA) secretion, indicating a potential in-site phytoremediation usage in the mining tailing regions of China.

  5. TORC1 signaling inhibition by rapamycin and caffeine affect lifespan, global gene expression, and cell proliferation of fission yeast.

    PubMed

    Rallis, Charalampos; Codlin, Sandra; Bähler, Jürg

    2013-08-01

    Target of rapamycin complex 1 (TORC1) is implicated in growth control and aging from yeast to humans. Fission yeast is emerging as a popular model organism to study TOR signaling, although rapamycin has been thought to not affect cell growth in this organism. Here, we analyzed the effects of rapamycin and caffeine, singly and combined, on multiple cellular processes in fission yeast. The two drugs led to diverse and specific phenotypes that depended on TORC1 inhibition, including prolonged chronological lifespan, inhibition of global translation, inhibition of cell growth and division, and reprograming of global gene expression mimicking nitrogen starvation. Rapamycin and caffeine differentially affected these various TORC1-dependent processes. Combined drug treatment augmented most phenotypes and effectively blocked cell growth. Rapamycin showed a much more subtle effect on global translation than did caffeine, while both drugs were effective in prolonging chronological lifespan. Rapamycin and caffeine did not affect the lifespan via the pH of the growth media. Rapamycin prolonged the lifespan of nongrowing cells only when applied during the growth phase but not when applied after cells had stopped proliferation. The doses of rapamycin and caffeine strongly correlated with growth inhibition and with lifespan extension. This comprehensive analysis will inform future studies into TORC1 function and cellular aging in fission yeast and beyond. PMID:23551936

  6. Spaceflight Alters Bacterial Gene Expression and Virulence and Reveals Role for Global Regulator Hfq

    NASA Technical Reports Server (NTRS)

    Wilson, J. W.; Ott, C. M.; zuBentrup, K. Honer; Ramamurthy R.; Quick, L.; Porwollik, S.; Cheng, P.; McClellan, M.; Tsaprailis, G.; Radabaugh, T.; Hunt, A.; Fernandez, D.; Richter, E.; Shah, M.; Kilcoyne, M.; Joshi, L.; Nelman-Gonzalez, M.; Hing, S.; Parra, M.; Dumaras, P.; Norwood, K.; Nickerson, C. A.; Bober, R.; Devich, J.; Ruggles, A.

    2007-01-01

    A comprehensive analysis of both the molecular genetic and phenotypic responses of any organism to the spaceflight environment has never been accomplished due to significant technological and logistical hurdles. Moreover, the effects of spaceflight on microbial pathogenicity and associated infectious disease risks have not been studied. The bacterial pathogen Salmonella typhimurium was grown aboard Space Shuttle mission STS-115 and compared to identical ground control cultures. Global microarray and proteomic analyses revealed 167 transcripts and 73 proteins changed expression with the conserved RNA-binding protein Hfq identified as a likely global regulator involved in the response to this environment. Hfq involvement was confirmed with a ground based microgravity culture model. Spaceflight samples exhibited enhanced virulence in a murine infection model and extracellular matrix accumulation consistent with a biofilm. Strategies to target Hfq and related regulators could potentially decrease infectious disease risks during spaceflight missions and provide novel therapeutic options on Earth.

  7. First cellular approach of the effects of global warming on groundwater organisms: a study of the HSP70 gene expression

    PubMed Central

    Morales, Anne; Hervant, Frédéric; Konecny, Lara; Moulin, Colette; Douady, Christophe J.

    2009-01-01

    Whereas the consequences of global warming at population or community levels are well documented, studies at the cellular level are still scarce. The study of the physiological or metabolic effects of such small increases in temperature (between +2°C and +6°C) is difficult because they are below the amplitude of the daily or seasonal thermal variations occurring in most environments. In contrast, subterranean biotopes are highly thermally buffered (±1°C within a year), and underground water organisms could thus be particularly well suited to characterise cellular responses of global warming. To this purpose, we studied genes encoding chaperone proteins of the HSP70 family in amphipod crustaceans belonging to the ubiquitous subterranean genus Niphargus. An HSP70 sequence was identified in eight populations of two complexes of species of the Niphargus genus (Niphargus rhenorhodanensis and Niphargus virei complexes). Expression profiles were determined for one of these by reverse transcription and quantitative polymerase chain reaction, confirming the inducible nature of this gene. An increase in temperature of 2°C seemed to be without effect on N. rhenorhodanensis physiology, whereas a heat shock of +6°C represented an important thermal stress for these individuals. Thus, this study shows that although Niphargus individuals do not undergo any daily or seasonal thermal variations in underground water, they display an inducible HSP70 heat shock response. This controlled laboratory-based physiological experiment constitutes a first step towards field investigations of the cellular consequences of global warming on subterranean organisms. PMID:19777376

  8. Horizontal gene transfer events reshape the global landscape of arm race between viruses and homo sapiens

    PubMed Central

    Chen, Dong-Sheng; Wu, Yi-Quan; Zhang, Wei; Jiang, San-Jie; Chen, Shan-Ze

    2016-01-01

    Horizontal gene transfer (HGT) drives the evolution of recipient organism particularly if it provides a novel function which enhances the fitness or its adaption to the environment. Virus-host co-evolution is attractive for studying co-evolutionary processes, since viruses strictly replicate inside of the host cells and thus their evolution is inexorably tangled with host biology. HGT, as a mechanism of co-evolution between human and viruses, has been widely documented, however, the roles HGT play during the interaction between human and viruses are still in their infancy. In this study, we performed a comprehensive analysis on the genes horizontally transferred between viruses and their corresponding human hosts. Our study suggests that the HGT genes in human are predominantly enriched in immune related GO terms while viral HGT genes are tend to be encoded by viruses which promote the invasion of immune system of hosts. Based on our results, it gives us a hint about the evolution trajectory of HGT events. Overall, our study suggests that the HGT between human and viruses are highly relevant to immune interaction and probably reshaped the arm race between hosts and viruses. PMID:27270140

  9. PARTNERS IN CRIME: GENES WITHIN AN AMPLICON COLLUDE TO GLOBALLY DEREGULATE CHROMATIN In LYMPHOMA

    PubMed Central

    Min, Dong-Joon; Licht, Jonathan D.

    2010-01-01

    In this issue of Cancer Cell, Rui et al. identify JAK2 and JMJDC2 as two contiguous, co-amplified oncogenes in primary mediastinal B-cell and Hodgkin lymphoma. Together JAK2 and JMJD2C induce major changes in chromatin structure and gene expression. Targeting theses protein with small molecules represents a new avenue for therapy. PMID:21156276

  10. Horizontal gene transfer events reshape the global landscape of arm race between viruses and homo sapiens.

    PubMed

    Chen, Dong-Sheng; Wu, Yi-Quan; Zhang, Wei; Jiang, San-Jie; Chen, Shan-Ze

    2016-01-01

    Horizontal gene transfer (HGT) drives the evolution of recipient organism particularly if it provides a novel function which enhances the fitness or its adaption to the environment. Virus-host co-evolution is attractive for studying co-evolutionary processes, since viruses strictly replicate inside of the host cells and thus their evolution is inexorably tangled with host biology. HGT, as a mechanism of co-evolution between human and viruses, has been widely documented, however, the roles HGT play during the interaction between human and viruses are still in their infancy. In this study, we performed a comprehensive analysis on the genes horizontally transferred between viruses and their corresponding human hosts. Our study suggests that the HGT genes in human are predominantly enriched in immune related GO terms while viral HGT genes are tend to be encoded by viruses which promote the invasion of immune system of hosts. Based on our results, it gives us a hint about the evolution trajectory of HGT events. Overall, our study suggests that the HGT between human and viruses are highly relevant to immune interaction and probably reshaped the arm race between hosts and viruses. PMID:27270140

  11. Global gene expression profile of normal and regenerating liver in young and old mice.

    PubMed

    Pibiri, Monica; Sulas, Pia; Leoni, Vera Piera; Perra, Andrea; Kowalik, Marta Anna; Cordella, Angela; Saggese, Pasquale; Nassa, Giovanni; Ravo, Maria

    2015-06-01

    The ability of the liver to regenerate and adjust its size after two/third partial hepatectomy (PH) is impaired in old rodents and humans. Here, we investigated by microarray analysis the expression pattern of hepatic genes in young and old untreated mice and the differences in gene expression profile following PH. Of the 10,237 messenger RNAs that had detectable expression, only 108 displayed a greater than 2-fold modification in gene expression levels between the two groups. These genes were involved in inflammatory and immune response, xenobiotics, and lipid and glucose metabolism. To identify the genes responsible for the different regenerative response, 10-week and 18-month-old mice subjected to PH were sacrificed at different time intervals after surgery. The results showed that 2463 transcripts had significantly different expression post PH between the two groups. However, in spite of impaired liver regeneration in old mice, cell cycle genes were similarly modified in both groups, the only exception being cyclin D1 gene which was up-regulated soon after PH in young mice, but mostly down-regulated in aged animals. Surprisingly, while in young hepatectomized mice, Yap messenger RNA (mRNA) expression was not significantly enhanced and protein expression essentially reflected the progression into cell cycle, its mRNA and protein levels were robustly increased in the liver of aged animals. Furthermore, a significant change of the age-related expression of the size regulator Yes-associated protein (YAP) was observed. Unexpectedly, while in young hepatectomized mice, Yap mRNA expression was not significantly enhanced and protein expression essentially reflected the progression into cell cycle, its mRNA and protein levels were robustly increased in the liver of aged animals. Moreover, when PH was performed on mitogen-induced enlarged livers, the earlier restoration of the original liver mass compared to animals subjected to PH only led to YAP down

  12. Global gene expression profile of normal and regenerating liver in young and old mice.

    PubMed

    Pibiri, Monica; Sulas, Pia; Leoni, Vera Piera; Perra, Andrea; Kowalik, Marta Anna; Cordella, Angela; Saggese, Pasquale; Nassa, Giovanni; Ravo, Maria

    2015-06-01

    The ability of the liver to regenerate and adjust its size after two/third partial hepatectomy (PH) is impaired in old rodents and humans. Here, we investigated by microarray analysis the expression pattern of hepatic genes in young and old untreated mice and the differences in gene expression profile following PH. Of the 10,237 messenger RNAs that had detectable expression, only 108 displayed a greater than 2-fold modification in gene expression levels between the two groups. These genes were involved in inflammatory and immune response, xenobiotics, and lipid and glucose metabolism. To identify the genes responsible for the different regenerative response, 10-week and 18-month-old mice subjected to PH were sacrificed at different time intervals after surgery. The results showed that 2463 transcripts had significantly different expression post PH between the two groups. However, in spite of impaired liver regeneration in old mice, cell cycle genes were similarly modified in both groups, the only exception being cyclin D1 gene which was up-regulated soon after PH in young mice, but mostly down-regulated in aged animals. Surprisingly, while in young hepatectomized mice, Yap messenger RNA (mRNA) expression was not significantly enhanced and protein expression essentially reflected the progression into cell cycle, its mRNA and protein levels were robustly increased in the liver of aged animals. Furthermore, a significant change of the age-related expression of the size regulator Yes-associated protein (YAP) was observed. Unexpectedly, while in young hepatectomized mice, Yap mRNA expression was not significantly enhanced and protein expression essentially reflected the progression into cell cycle, its mRNA and protein levels were robustly increased in the liver of aged animals. Moreover, when PH was performed on mitogen-induced enlarged livers, the earlier restoration of the original liver mass compared to animals subjected to PH only led to YAP down

  13. Salmonella SirA is a global regulator of genes mediating enteropathogenesis.

    PubMed

    Ahmer, B M; van Reeuwijk, J; Watson, P R; Wallis, T S; Heffron, F

    1999-02-01

    SirA of Salmonella typhimurium is known to regulate the hilA and prgH genes within Salmonella pathogenicity island 1 (SPI1). To identify more members of the SirA regulon, we screened 10,000 random lacZY fusions (chromosomal MudJ insertions) for regulation by SirA and identified 10 positively regulated fusions. Three fusions were within the SPI1 genes hilA (an SPI1 transcriptional regulator), spaS (a component of the SPI1 type III export apparatus) and sipB (a substrate of the SPI1 export apparatus). Two fusions were within the sopB gene (also known as sigD). sopB is located within SPI5, but encodes a protein that is exported via the SPI1 export apparatus. In addition, five fusions were within genes of unknown function that are located in SPI4. As spaS and sipB were likely to be hilA dependent, we tested all of the fusions (except hilA) for hilA dependence. Surprisingly, we found that all of the fusions require hilA for expression and that plasmid-encoded SirA cannot bypass this requirement. Therefore, SirA regulates hilA, the product of which regulates genes within SPI1, SPI4 and SPI5. Both sirA and hilA mutants are dramatically attenuated in a bovine model of gastroenteritis, but have little or no effect in the mouse model of typhoid fever. This study establishes the SirA/HilA regulatory cascade as the primary regulon controlling enteropathogenic virulence functions in S. typhimurium. Because S. typhimurium causes gastroenteritis in both cattle and humans, we believe that this information may be directly applicable to the human disease.

  14. Changes of global gene expression and secondary metabolite accumulation during light-dependent Aspergillus nidulans development.

    PubMed

    Bayram, Özgür; Feussner, Kirstin; Dumkow, Marc; Herrfurth, Cornelia; Feussner, Ivo; Braus, Gerhard H

    2016-02-01

    Fungal development and secondary metabolite production are coordinated by regulatory complexes as the trimeric velvet complex. Light accelerates asexual but decreases sexual development of the filamentous fungus Aspergillus nidulans. Changes in gene expression and secondary metabolite accumulation in response to environmental stimuli have been the focus of many studies, but a comprehensive comparison during entire development is lacking. We compared snapshots of transcript and metabolite profiles during fungal development in dark or light. Overall 2.014 genes corresponding to 19% of the genome were differentially expressed when submerged vegetative hyphae were compared to surface development. Differentiation was preferentially asexual in light or preferentially sexual connected to delayed asexual development in dark. Light induces significantly gene expression within the first 24-48h after the transfer to surfaces. Many light induced genes are also expressed in dark after a delay of up to two days, which might be required for preparation of enhanced sexual development. Darkness results in a massive transcriptional reprogramming causing a peak of lipid-derived fungal pheromone synthesis (psi factors) during early sexual development and the expression of genes for cell-wall degradation presumably to mobilize the energy for sexual differentiation. Accumulation of secondary metabolites like antitumoral terrequinone A or like emericellamide start under light conditions, whereas the mycotoxin sterigmatocystin or asperthecin and emodin appear under dark conditions during sexual development. Amino acid synthesis and pool rapidly drop after 72-96h in dark. Subsequent initiation of apoptotic cell-death pathways in darkness happens significantly later than in light. This illustrates that fungal adaptation in differentiation and secondary metabolite production to light conditions requires the reprogramming of one fifth of the potential of its genome.

  15. Rotating wall vessel exposure alters protein secretion and global gene expression in Staphylococcus aureus

    NASA Astrophysics Data System (ADS)

    Rosado, Helena; O'Neill, Alex J.; Blake, Katy L.; Walther, Meik; Long, Paul F.; Hinds, Jason; Taylor, Peter W.

    2012-04-01

    Staphylococcus aureus is routinely recovered from air and surface samples taken aboard the International Space Station (ISS) and poses a health threat to crew. As bacteria respond to the low shear forces engendered by continuous rotation conditions in a Rotating Wall Vessel (RWV) and the reduced gravitational field of near-Earth flight by altering gene expression, we examined the effect of low-shear RWV growth on protein secretion and gene expression by three S. aureus isolates. When cultured under 1 g, the total amount of protein secreted by these strains varied up to fourfold; under continuous rotation conditions, protein secretion by all three strains was significantly reduced. Concentrations of individual proteins were differentially reduced and no evidence was found for increased lysis. These data suggest that growth under continuous rotation conditions reduces synthesis or secretion of proteins. A limited number of changes in gene expression under continuous rotation conditions were noted: in all isolates vraX, a gene encoding a polypeptide associated with cell wall stress, was down-regulated. A vraX deletion mutant of S. aureus SH1000 was constructed: no differences were found between SH1000 and ΔvraX with respect to colony phenotype, viability, protein export, antibiotic susceptibility, vancomycin kill kinetics, susceptibility to cold or heat and gene modulation. An ab initio protein-ligand docking simulation suggests a major binding site for β-lactam drugs such as imipenem. If such changes to the bacterial phenotype occur during spaceflight, they will compromise the capacity of staphylococci to cause systemic infection and to circumvent antibacterial chemotherapy.

  16. Mining the earth

    SciTech Connect

    Young, J.E.

    1992-01-01

    Substances extracted from the earth - stone, iron, bronze - have been so critical to human development that historians name the ages of our past after them. But while scholars have carefully tracked human use of minerals, they have never accounted for the vast environmental damage incurred in mineral production. Few people would guess that a copper mining operation has removed a piece of Utah seven times the weight of all the material dug for the Panama Canal. Few would dream that mines and smelters take up to a tenth of all the energy used each year, or that the waste left by mining measures in the billions of tons - dwarfing the world's total accumulation of more familiar kinds of waste, such as municipal garbage. Indeed, more material is now stripped from the earth by mining than by all the natural erosion of the earth's rivers. The effects of mining operations on the environment are discussed under the following topics: minerals in the global economy, laying waste, at what cost cleaning up, and dipping out. It is concluded that in the long run, the most effective strategy for minimizing new damage is not merely to make mineral extraction cleaner, but to reduce the rich nations needs for virgin (non-recycled) minerals.

  17. Allele mining in the gene pool of wild Solanum species for homologues of late blight resistance gene RB/Rpi-blb1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Solanum bulbocastanum comprising a CC-NBS-LRR gene RB/Rpi-blb1 confers broad-spectrum resistance to Phytophthora infestans and is currently employed in potato breeding for durable late blight (LB) resistance. Genomes of several Solanum species were reported to contain RB homologues with confirmed b...

  18. African mining

    SciTech Connect

    Not Available

    1987-01-01

    This book contains papers presented at a conference addressing the development of the minerals industry in Africa. Topics covered include: A review - past, present and future - of Zimbabwe's mining industry; Geomorphological processes and related mineralization in Tanzania; and Rock mechanics investigations at Mufulira mine, Zambia.

  19. Global genome repair of 8-oxoG in hamster cells requires a functional CSB gene product.

    PubMed

    Sunesen, Morten; Stevnsner, Tinna; Brosh, Robert M; Dianov, Grigory L; Bohr, Vilhelm A

    2002-05-16

    Cockayne syndrome (CS) is an autosomal recessive human disease characterized by UV-sensitivity as well as neurological and developmental abnormalities. Two complementation groups have been established, designated CS-A and CS-B. Traditionally, CSA and CSB have been ascribed a function in the transcription-coupled repair (TCR) pathway of nucleotide excision repair (NER) that efficiently removes bulky lesions from the transcribed strand of RNA polymerase II transcribed genes. To assess the role of the CSB protein in the repair of the highly mutagenic base lesion 7,8-dihydro-8-oxoguanine (8-oxoG), we have investigated the removal of this lesion using an in vitro incision approach with cell extracts as well as an in vivo approach with a modified protocol of the gene-specific repair assay, which allows the measurement of base lesion repair in intragenomic sequences. Our results demonstrate that the integrity of the CSB protein is pivotal for processes leading to incision at the site of 8-oxoG and that the global genome repair (GGR) of this lesion requires a functional CSB gene product in vivo. PMID:12032859

  20. Global Gene Expression Profiling in Interleukin-12-Induced Activation of CD8+ Cytotoxic T Lymphocytes against Mouse Mammary Carcinoma

    PubMed Central

    Cao, Shanjin; Xiang, Zhaoying; Ma, Xiaojing

    2010-01-01

    Interleukin-12 (IL-12) is a critical cytokine representing the link between the cellular and humoral branches of host immune defense apparatus. IL-12-induced cytotoxic lymphocyte (CTL) development is a central mechanism in immune responses against intracellular infectious agents as well as malignant growth. However, the molecular basis of tumor-specific CTL responses mediated by IL-12 remains poorly defined. In this study, we addressed this issue in a comprehensive manner to probe into IL-12-induced anti-tumor responses by global gene expression profiling of mRNA expression in CD8+T cells in a transplantable syngeneic mouse mammary carcinoma model treated or not with recombinant IL-12. A strong tumor regression was induced by the IL-12 treatment. An introspection of differential gene expression at an early stage of the IL-12-initiated CTL activation reveals interesting genes and molecular pathways that may account for the marked tumor regression, and is likely to provide a rich source of potential targets for further research and development of effective therapeutic modalities. PMID:16285895

  1. Analysis of 23S rRNA genes in metagenomes - a case study from the Global Ocean Sampling Expedition.

    PubMed

    Yilmaz, Pelin; Kottmann, Renzo; Pruesse, Elmar; Quast, Christian; Glöckner, Frank Oliver

    2011-09-01

    As an evolutionary marker, 23S ribosomal RNA (rRNA) offers more diagnostic sequence stretches and greater sequence variation than 16S rRNA. However, 23S rRNA is still not as widely used. Based on 80 metagenome samples from the Global Ocean Sampling (GOS) Expedition, the usefulness and taxonomic resolution of 23S rRNA were compared to those of 16S rRNA. Since 23S rRNA is approximately twice as large as 16S rRNA, twice as many 23S rRNA gene fragments were retrieved from the GOS reads than 16S rRNA gene fragments, with 23S rRNA gene fragments being generally about 100bp longer. Datasets for 16S and 23S rRNA sequences revealed similar relative abundances for major marine bacterial and archaeal taxa. However, 16S rRNA sequences had a better taxonomic resolution due to their significantly larger reference database. Reevaluation of the specificity of previously published PCR amplification primers and group specific fluorescence in situ hybridization probes on this metagenomic set of non-amplified 23S rRNA sequences revealed that out of 16 primers investigated, only two had more than 90% target group coverage. Evaluations of two probes, BET42a and GAM42a, were in accordance with previous evaluations, with a discrepancy in the target group coverage of the GAM42a probe when evaluated against the GOS metagenomic dataset.

  2. Extending mine life

    SciTech Connect

    Not Available

    1984-06-01

    Mine layouts, new machines and techniques, research into problem areas of ground control and so on, are highlighted in this report on extending mine life. The main resources taken into account are coal mining, uranium mining, molybdenum and gold mining.

  3. Differential global and extra-cellular matrix focused gene expression patterns between normal and glaucomatous human lamina cribrosa cells

    PubMed Central

    Wordinger, Robert J.; Clark, Abbot F.; O'Brien, Colm J.

    2009-01-01

    Purpose Marked extracellular matrix (ECM) remodeling occurs in the human optic nerve head in primary open angle glaucoma (POAG). The glial fibrillary acid protein (GFAP) negative lamina cribrosa cell may play an important role in this remodeling process. We report the first study of global and ECM-focused gene transcription differentials between GFAP-negative lamina cribrosa (LC) cells from normal and POAG human donors. Methods GFAP-negative LC cell lines were generated from the optic nerve tissue of four normal (n=4) and four POAG (n=4) human donors. Using Affymetrix U133A arrays the transcriptional profile between the normal and diseased groups were compared. Bioinformatic analysis was performed using robust multichip average (RMA Express) and EASE/David. Real time TaqMan PCR and immunohistochemistry analyses were performed to validate the microarray data. Results 183 genes were upregulated by greater than 1.5 fold and 220 were down regulated by greater than 1.5 fold in the POAG LC cells versus normal controls. Upregulated genes in POAG LC cells included, transforming growth factor beta 1 (TGFβ1), secreted acid protein cysteine rich (SPARC), periostin (POSTN), thrombospondin-1 (THBS1), cartilage linking protein-1 (CRTL-1), and collagen type I (COL1A1), collagen type V (COL5A1), and collagen type XI (COL11A1). Downregulated ECM genes in POAG included fibulin 1 (FBLN1), decorin (DCN), and collagen type XVIII (COL18A1). All TaqMan PCR validation assays were significant (*p<0.05) and consistent with the array data. Immunohistochemistry of one target (periostin) confirmed its differential expression at the protein level in POAG optic nerve head tissue compared with non-glaucomatous controls. Functional annotation and over-representation analysis identified ECM genes as a statistically over-represented class of genes in POAG LC cells compared with normal LC cells. Conclusions This study reports for the first time that POAG LC cells in-vitro demonstrate upregulated ECM

  4. Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening

    PubMed Central

    LING, SHIZHANG; RETTIG, ELENI M.; TAN, MARIETTA; CHANG, XIAOFEI; WANG, ZHIMING; BRAIT, MARIANA; BISHOP, JUSTIN A.; FERTIG, ELANA J.; CONSIDINE, MICHAEL; WICK, MICHAEL J.; HA, PATRICK K.

    2016-01-01

    Salivary gland adenoid cystic carcinoma (ACC) is a rare head and neck malignancy without molecular biomarkers that can be used to predict the chemotherapeutic response or prognosis of ACC. The regulation of gene expression of oncogenes and tumor suppressor genes (TSGs) through DNA promoter methylation may play a role in the carcinogenesis of ACC. To identify differentially methylated genes in ACC, a global demethylating agent, 5-aza-2′-deoxycytidine (5-AZA) was utilized to unmask putative TSG silencing in ACC xenograft models in mice. Fresh xenografts were passaged, implanted in triplicate in mice that were treated with 5-AZA daily for 28 days. These xenografts were then evaluated for genome-wide DNA methylation patterns using the Illumina Infinium HumanMethylation27 BeadChip array. Validation of the 32 candidate genes was performed by bisulfite sequencing (BS-seq) in a separate cohort of 6 ACC primary tumors and 6 normal control salivary gland tissues. Hypermethylation was identified in the HCN2 gene promoter in all 6 control tissues, but hypomethylation was found in all 6 ACC tumor tissues. Quantitative validation of HCN2 promoter methylation level in the region detected by BS-seq was performed in a larger cohort of primary tumors (n=32) confirming significant HCN2 hypomethylation in ACCs compared with normal samples (n=10; P=0.04). HCN2 immunohistochemical staining was performed on an ACC tissue microarray. HCN2 staining intensity and H-score, but not percentage of the positively stained cells, were significantly stronger in normal tissues than those of ACC tissues. With our novel screening and sequencing methods, we identified several gene candidates that were methylated. The most significant of these genes, HCN2, was actually hypomethylated in tumors. However, promoter methylation status does not appear to be a major determinant of HCN2 expression in normal and ACC tissues. HCN2 hypomethylation is a biomarker of ACC and may play an important role in the

  5. Further Insights into the Mode of Action of the Lipoglycopeptide Telavancin through Global Gene Expression Studies

    PubMed Central

    Song, Yang; Lunde, Christopher S.; Benton, Bret M.

    2012-01-01

    Telavancin is a novel semisynthetic lipoglycopeptide derivative of vancomycin with a decylaminoethyl side chain that is active against Gram-positive bacteria, including Staphylococcus aureus strains resistant to methicillin or vancomycin. A dual mechanism of action has been proposed for telavancin involving inhibition of peptidoglycan biosynthesis and membrane depolarization. Here we report the results of genome-wide transcriptional profiling of the response of S. aureus to telavancin using microarrays. Short (15-min) challenge of S. aureus with telavancin revealed strong expression of the cell wall stress stimulon, a characteristic response to inhibition of cell wall biosynthesis. In the transcriptome obtained after 60-min telavancin challenge, in addition to induction of the cell wall stress stimulon, there was induction of various genes, including lrgA and lrgB, lysine biosynthesis operon (dap) genes, vraD and vraE, and hlgC, that have been reported to be induced by known membrane-depolarizing and active agents, including carbonyl cyanide m-chlorophenylhydrazone, daptomycin, bacitracin, and other antimicrobial peptides These genes were either not induced or only weakly induced by the parent molecule vancomycin. We suggest that expression of these genes is a response of the cell to mitigate and detoxify such molecules and is diagnostic of a membrane-depolarizing or membrane-active molecule. The results indicate that telavancin causes early and significant induction of the cell wall stress stimulon due to strong inhibition of peptidoglycan biosynthesis, with evidence in support of membrane depolarization and membrane activity that is expressed after a longer duration of drug treatment. PMID:22411615

  6. Comparison of the global gene expression profiles in the bovine endometrium between summer and autumn.

    PubMed

    Sakumoto, Ryosuke; Hayashi, Ken-Go; Saito, Shiori; Kanahara, Hiroko; Kizaki, Keiichiro; Iga, Kosuke

    2015-01-01

    Heat stress compromises fertility during summer in dairy and beef cows by causing nutritional, physiological and reproductive damages. To examine the difference in endometrial conditions in cows between summer and autumn, gene expression profiles were compared using a 15 K bovine oligo DNA microarray. The trial was conducted in the summer (early in September) and autumn (mid-November) seasons of two consecutive years (2013-2014) in Morioka, Japan. Endometrial samples were collected from the cows using a biopsy technique. The expressions of 268 genes were significantly higher in the endometrium collected in summer than those collected in autumn, whereas the expressions of 369 genes were lower (P<0.05 or lower). Messenger RNA expressions of glycoprotein 2 (GP2), neurotensin (NTS),E-cadherin (CDH1) and heat shock 105kDa/110kDa protein 1 (HSPH1) were validated by quantitative real-time PCR. Transcripts of GP2 and NTS were more abundant in the endometrium from summer than in the endometrium from autumn (P < 0.05). In contrast, the mRNA expressions of CDH1 were lower (P < 0.05) and those of HSPH1 tended to be low (P = 0.09) in the endometrium from summer. Immunohistochemical staining showed that GP2, NTS and HSPH1 were expressed in the endometrial epithelial or glandular epithelial cells. The serum concentrations of NTS collected from the cows in summer were higher than those collected from cows in autumn (P < 0.05). Collectively, the different gene expression profiles may contribute to functional differences in the endometrium between summer and autumn, and the increases in GP2 and NTS may have a relationship with the endometrial deficiency that causes infertility of cows in summer.

  7. Comparison of the global gene expression profiles in the bovine endometrium between summer and autumn

    PubMed Central

    SAKUMOTO, Ryosuke; HAYASHI, Ken-Go; SAITO, Shiori; KANAHARA, Hiroko; KIZAKI, Keiichiro; IGA, Kosuke

    2015-01-01

    Heat stress compromises fertility during summer in dairy and beef cows by causing nutritional, physiological and reproductive damages. To examine the difference in endometrial conditions in cows between summer and autumn, gene expression profiles were compared using a 15 K bovine oligo DNA microarray. The trial was conducted in the summer (early in September) and autumn (mid-November) seasons of two consecutive years (2013–2014) in Morioka, Japan. Endometrial samples were collected from the cows using a biopsy technique. The expressions of 268 genes were significantly higher in the endometrium collected in summer than those collected in autumn, whereas the expressions of 369 genes were lower (P<0.05 or lower). Messenger RNA expressions of glycoprotein 2 (GP2), neurotensin (NTS),E-cadherin (CDH1) and heat shock 105kDa/110kDa protein 1 (HSPH1) were validated by quantitative real-time PCR. Transcripts of GP2 and NTS were more abundant in the endometrium from summer than in the endometrium from autumn (P < 0.05). In contrast, the mRNA expressions of CDH1 were lower (P < 0.05) and those of HSPH1 tended to be low (P = 0.09) in the endometrium from summer. Immunohistochemical staining showed that GP2, NTS and HSPH1 were expressed in the endometrial epithelial or glandular epithelial cells. The serum concentrations of NTS collected from the cows in summer were higher than those collected from cows in autumn (P < 0.05). Collectively, the different gene expression profiles may contribute to functional differences in the endometrium between summer and autumn, and the increases in GP2 and NTS may have a relationship with the endometrial deficiency that causes infertility of cows in summer. PMID:25994242

  8. Global depression in gene expression as a response to rapid thermal changes in vent mussels.

    PubMed

    Boutet, Isabelle; Tanguy, Arnaud; Le Guen, Dominique; Piccino, Patrice; Hourdez, Stéphane; Legendre, Pierre; Jollivet, Didier

    2009-09-01

    Hydrothermal vent mussels belonging to the genus Bathymodiolus are distributed worldwide and dominate communities at shallow Atlantic hydrothermal sites. While organisms inhabiting coastal ecosystems are subjected to predictable oscillations of physical and chemical variables owing to tidal cycles, the vent mussels sustain pronounced temperature changes over short periods of time, correlated to the alternation of oxic/anoxic phases. In this context, we focused on the short-term adaptive response of mussels to temperature change at a molecular level. The mRNA expression of 23 genes involved in various cell functions of the vent mussel Bathymodiolus azoricus was followed after heat shocks for either 30 or 120 min, at 25 and 30 degrees C over a 48 h recovery period at 5 degrees C. Mussels were genotyped at 10 enzyme loci to explore a relationship between natural genetic variation, gene expression and temperature adaptation. Results indicate that the mussel response to increasing temperature is a depression in gene expression, such a response being genotypically correlated at least for the Pgm-1 locus. This suggests that an increase in temperature could be a signal triggering anaerobiosis for B. azoricus or this latter alternatively behaves more like a 'cold' stenotherm species, an attribute more related to its phylogenetic history, a cold seeps/wood fall origin.

  9. Multiple gene evidence for expansion of extant penguins out of Antarctica due to global cooling.

    PubMed

    Baker, Allan J; Pereira, Sergio Luiz; Haddrath, Oliver P; Edge, Kerri-Anne

    2006-01-01

    Classic problems in historical biogeography are where did penguins originate, and why are such mobile birds restricted to the Southern Hemisphere? Competing hypotheses posit they arose in tropical-warm temperate waters, species-diverse cool temperate regions, or in Gondwanaland approximately 100 mya when it was further north. To test these hypotheses we constructed a strongly supported phylogeny of extant penguins from 5851 bp of mitochondrial and nuclear DNA. Using Bayesian inference of ancestral areas we show that an Antarctic origin of extant taxa is highly likely, and that more derived taxa occur in lower latitudes. Molecular dating estimated penguins originated about 71 million years ago in Gondwanaland when it was further south and cooler. Moreover, extant taxa are inferred to have originated in the Eocene, coincident with the extinction of the larger-bodied fossil taxa as global climate cooled. We hypothesize that, as Antarctica became ice-encrusted, modern penguins expanded via the circumpolar current to oceanic islands within the Antarctic Convergence, and later to the southern continents. Thus, global cooling has had a major impact on penguin evolution, as it has on vertebrates generally. Penguins only reached cooler tropical waters in the Galapagos about 4 mya, and have not crossed the equatorial thermal barrier.

  10. A global transcriptional regulator in Thermococcus kodakaraensis controls the expression levels of both glycolytic and gluconeogenic enzyme-encoding genes.

    PubMed

    Kanai, Tamotsu; Akerboom, Jasper; Takedomi, Shogo; van de Werken, Harmen J G; Blombach, Fabian; van der Oost, John; Murakami, Taira; Atomi, Haruyuki; Imanaka, Tadayuki

    2007-11-16

    We identified a novel regulator, Thermococcales glycolytic regulator (Tgr), functioning as both an activator and a repressor of transcription in the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1. Tgr (TK1769) displays similarity (28% identical) to Pyrococcus furiosus TrmB (PF1743), a transcriptional repressor regulating the trehalose/maltose ATP-binding cassette transporter genes, but is more closely related (67%) to a TrmB paralog in P. furiosus (PF0124). Growth of a tgr disruption strain (Deltatgr) displayed a significant decrease in growth rate under gluconeogenic conditions compared with the wild-type strain, whereas comparable growth rates were observed under glycolytic conditions. A whole genome microarray analysis revealed that transcript levels of almost all genes related to glycolysis and maltodextrin metabolism were at relatively high levels in the Deltatgr mutant even under gluconeogenic conditions. The Deltatgr mutant also displayed defects in the transcriptional activation of gluconeogenic genes under these conditions, indicating that Tgr functions as both an activator and a repressor. Genes regulated by Tgr contain a previously identified sequence motif, the Thermococcales glycolytic motif (TGM). The TGM was positioned upstream of the Transcription factor B-responsive element (BRE)/TATA sequence in gluconeogenic promoters and downstream of it in glycolytic promoters. Electrophoretic mobility shift assay indicated that recombinant Tgr protein specifically binds to promoter regions containing a TGM. Tgr was released from the DNA when maltotriose was added, suggesting that this sugar is most likely the physiological effector. Our results strongly suggest that Tgr is a global transcriptional regulator that simultaneously controls, in response to sugar availability, both glycolytic and gluconeogenic metabolism in T. kodakaraensis via its direct binding to the TGM.

  11. Global gene expression and the role of sigma factors in Neisseria gonorrhoeae in interactions with epithelial cells.

    PubMed

    Du, Ying; Lenz, Jonathan; Arvidson, Cindy Grove

    2005-08-01

    Like many bacterial pathogens, Neisseria gonorrhoeae must adapt to environmental changes in order to successfully colonize and proliferate in a new host. Modulation of gene expression in response to environmental signals is an efficient mechanism used by bacteria to achieve this goal. Using DNA microarrays and a tissue culture model for gonococcal infection, we examined global changes in gene expression in N. gonorrhoeae in response to adherence to host cells. Among those genes induced upon adherence to human epithelial cells in culture was rpoH, which encodes a homolog of the heat shock sigma factor, sigma(32) (RpoH), as well as genes of the RpoH regulon, groEL and groES. Attempts to construct an rpoH null mutant in N. gonorrhoeae were unsuccessful, suggesting that RpoH is essential for viability of N. gonorrhoeae. The extracytoplasmic sigma factor, RpoE (sigma(E)), while known to regulate rpoH in other bacteria, was found not to be necessary for the up-regulation of rpoH in gonococci upon adherence to host cells. To examine the role of RpoH in host cell interactions, an N. gonorrhoeae strain conditionally expressing rpoH was constructed. The results of our experiments showed that while induction of rpoH expression is not necessary for adherence of gonococci to epithelial cells, it is important for the subsequent invasion step, as gonococci depleted for rpoH invade cells two- to threefold less efficiently than a wild-type strain. Taken together, these results indicate that sigma(32), but not sigma(E), is important for the response of gonococci in the initial steps of an infection. PMID:16040997

  12. Global methylation silencing of clustered proto-cadherin genes in cervical cancer: serving as diagnostic markers comparable to HPV.

    PubMed

    Wang, Kai-Hung; Lin, Cuei-Jyuan; Liu, Chou-Jen; Liu, Dai-Wei; Huang, Rui-Lan; Ding, Dah-Ching; Weng, Ching-Feng; Chu, Tang-Yuan

    2015-01-01

    Epigenetic remodeling of cell adhesion genes is a common phenomenon in cancer invasion. This study aims to investigate global methylation of cell adhesion genes in cervical carcinogenesis and to apply them in early detection of cancer from cervical scraping. Genome-wide methylation array was performed on an investigation cohort, including 16 cervical intraepithelial neoplasia 3 (CIN3) and 20 cervical cancers (CA) versus 12 each of normal, inflammation and CIN1 as controls. Twelve members of clustered proto-cadherin (PCDH) genes were collectively methylated and silenced, which were validated in cancer cells of the cervix, endometrium, liver, head and neck, breast, and lung. In an independent cohort including 107 controls, 66 CIN1, 85 CIN2/3, and 38 CA, methylated PCDHA4 and PCDHA13 were detected in 2.8%, 24.2%, 52.9%, and 84.2% (P < 10(-25) ), and 2.8%, 24.2%, 50.6%, and 94.7% (P < 10(-29) ), respectively. In diagnosis of CIN2 or more severe lesion of the cervix, a combination test of methylated PCDHA4 or PCDHA13 from cervical scraping had a sensitivity, specificity, positive predictive value, and negative predictive value of 74.8%, 80.3%, 73%, and 81.8%, respectively. Testing of this combination from cervical scraping is equally sensitive but more specific than human papillomavirus (HPV) test in diagnosis of CIN2 or more severe lesions. The study disclosed a collective methylation of PCDH genes in cancer of cervix and other sites. At least two of them can be promising diagnostic markers for cervical cancer noninferior to HPV.

  13. Heterologous expression of natural product biosynthetic gene clusters in Streptomyces coelicolor: from genome mining to manipulation of biosynthetic pathways.

    PubMed

    Gomez-Escribano, Juan Pablo; Bibb, Mervyn J

    2014-02-01

    Heterologous gene expression is one of the main strategies used to access the full biosynthetic potential of actinomycetes, as well as to study the metabolic pathways of natural product biosynthesis and to create unnatural pathways. Streptomyces coelicolor A3(2) is the most studied member of the actinomycetes, bacteria renowned for their prolific capacity to synthesize a wide range of biologically active specialized metabolites. We review here the use of strains of this species for the heterologous production of structurally diverse actinomycete natural products.

  14. Diversity of Dissimilatory Sulfite Reductase Genes (dsrAB) in a Salt Marsh Impacted by Long-Term Acid Mine Drainage▿ †

    PubMed Central

    Moreau, John W.; Zierenberg, Robert A.; Banfield, Jillian F.

    2010-01-01

    Sulfate-reducing bacteria (SRB) play a major role in the coupled biogeochemical cycling of sulfur and chalcophilic metal(loid)s. By implication, they can exert a strong influence on the speciation and mobility of multiple metal(loid) contaminants. In this study, we combined DsrAB gene sequencing and sulfur isotopic profiling to identify the phylogeny and distribution of SRB and to assess their metabolic activity in salt marsh sediments exposed to acid mine drainage (AMD) for over 100 years. Recovered dsrAB sequences from three sites sampled along an AMD flow path indicated the dominance of a single Desulfovibrio species. Other major sequence clades were related most closely to Desulfosarcina, Desulfococcus, Desulfobulbus, and Desulfosporosinus species. The presence of metal sulfides with low δ34S values relative to δ34S values of pore water sulfate showed that sediment SRB populations were actively reducing sulfate under ambient conditions (pH of ∼2), although possibly within less acidic microenvironments. Interestingly, δ34S values for pore water sulfate were lower than those for sulfate delivered during tidal inundation of marsh sediments. 16S rRNA gene sequence data from sediments and sulfur isotope data confirmed that sulfur-oxidizing bacteria drove the reoxidation of biogenic sulfide coupled to oxygen or nitrate reduction over a timescale of hours. Collectively, these findings imply a highly dynamic microbially mediated cycling of sulfate and sulfide, and thus the speciation and mobility of chalcophilic contaminant metal(loid)s, in AMD-impacted marsh sediments. PMID:20472728

  15. De novo characterization of the Dialeurodes citri transcriptome: mining genes involved in stress resistance and simple sequence repeats (SSRs) discovery.

    PubMed

    Chen, E-H; Wei, D-D; Shen, G-M; Yuan, G-R; Bai, P-P; Wang, J-J

    2014-02-01

    The citrus whitefly, Dialeurodes citri (Ashmead), is one of the three economically important whitefly species that infest citrus plants around the world; however, limited genetic research has been focused on D. citri, partly because of lack of genomic resources. In this study, we performed de novo assembly of a transcriptome using Illumina paired-end sequencing technology (Illumina Inc., San Diego, CA, USA). In total, 36,766 unigenes with a mean length of 497 bp were identified. Of these unigenes, we identified 17,788 matched known proteins in the National Center for Biotechnology Information database, as determined by Blast search, with 5731, 4850 and 14,441 unigenes assigned to clusters of orthologous groups (COG), gene ontology (GO), and SwissProt, respectively. In total, 7507 unigenes were assigned to 308 known pathways. In-depth analysis of the data showed that 117 unigenes were identified as potentially involved in the detoxification of xenobiotics and 67 heat shock protein (Hsp) genes were associated with environmental stress. In addition, these enzymes were searched against the GO and COG database, and the results showed that the three major detoxification enzymes and Hsps were classified into 18 and 3, 6, and 8 annotations, respectively. In addition, 149 simple sequence repeats were detected. The results facilitate the investigation of molecular resistance mechanisms to insecticides and environmental stress, and contribute to molecular marker development. The findings greatly improve our genetic understanding of D. citri, and lay the foundation for future functional genomics studies on this species.

  16. Genome mining of astaxanthin biosynthetic genes from Sphingomonas sp. ATCC 55669 for heterologous overproduction in Escherichia coli

    PubMed Central

    Ma, Tian; Zhou, Yuanjie; Li, Xiaowei; Zhu, Fayin; Cheng, Yongbo; Liu, Yi; Deng, Zixin

    2015-01-01

    Abstract As a highly valued keto‐carotenoid, astaxanthin is widely used in nutritional supplements and pharmaceuticals. Therefore, the demand for biosynthetic astaxanthin and improved efficiency of astaxanthin biosynthesis has driven the investigation of metabolic engineering of native astaxanthin producers and heterologous hosts. However, microbial resources for astaxanthin are limited. In this study, we found that the α‐Proteobacterium Sphingomonas sp. ATCC 55669 could produce astaxanthin naturally. We used whole‐genome sequencing to identify the astaxanthin biosynthetic pathway using a combined PacBio‐Illumina approach. The putative astaxanthin biosynthetic pathway in Sphingomonas sp. ATCC 55669 was predicted. For further confirmation, a high‐efficiency targeted engineering carotenoid synthesis platform was constructed in E. coli for identifying the functional roles of candidate genes. All genes involved in astaxanthin biosynthesis showed discrete distributions on the chromosome. Moreover, the overexpression of exogenous E. coli idi in Sphingomonas sp. ATCC 55669 increased astaxanthin production by 5.4‐fold. This study described a new astaxanthin producer and provided more biosynthesis components for bioengineering of astaxanthin in the future. PMID:26580858

  17. 17α-Ethinylestradiol (EE2) effect on global gene expression in primary rainbow trout (Oncorhynchus mykiss) hepatocytes.

    PubMed

    Hultman, Maria T; Song, You; Tollefsen, Knut Erik

    2015-12-01

    The potential impact of endocrine disrupting chemicals (EDCs) in the aquatic environment has driven the development of screening assays to evaluate the estrogenic properties of chemicals and their effects on aquatic organisms such as fish. However, obtaining full concentration-response relationships in animal (in vivo) exposure studies are laborious, costly and unethical, hence a need for developing feasible alternative (non-animal) methods. Use of in vitro bioassays such as primary fish hepatocytes, which retain many of the native properties of the liver, has been proposed for in vitro screening of estrogen receptor (ER) agonists and antagonists. The aim of present study was to characterize the molecular mode of action (MoA) of the ER agonist 17α-ethinylestradiol (EE2) in primary rainbow trout (Oncorhynchus mykiss) hepatocytes. A custom designed salmonid 60,000-feature (60k) oligonucleotide microarray was used to characterize the potential MoAs after 48h exposure to EE2. The microarray analysis revealed several concentration-dependent gene expression alterations including classical estrogen sensitive biomarker gene expression (e.g. estrogen receptor α, vitellogenin, zona radiata). Gene Ontology (GO) analysis displayed transcriptional changes suggesting interference of cellular growth, fatty acid and lipid metabolism potentially mediated through the estrogen receptor (ER), which were proposed to be associated with modulation of genes involved in endocrine function and reproduction. Pathway analysis supported the identified GOs and revealed modulation of additional genes associated with apoptosis and cholesterol biosynthesis. Differentially expressed genes (DEGs) related to impaired lipid metabolism (e.g. peroxisome proliferator-activated receptor α and γ), growth (e.g. insulin growth factor protein 1), phase I and II biotransformation (e.g. cytochrome P450 1A, sulfotransferase, UDP-glucuronosyltransferase and glutathione S-transferase) provided additional

  18. 17α-Ethinylestradiol (EE2) effect on global gene expression in primary rainbow trout (Oncorhynchus mykiss) hepatocytes.

    PubMed

    Hultman, Maria T; Song, You; Tollefsen, Knut Erik

    2015-12-01

    The potential impact of endocrine disrupting chemicals (EDCs) in the aquatic environment has driven the development of screening assays to evaluate the estrogenic properties of chemicals and their effects on aquatic organisms such as fish. However, obtaining full concentration-response relationships in animal (in vivo) exposure studies are laborious, costly and unethical, hence a need for developing feasible alternative (non-animal) methods. Use of in vitro bioassays such as primary fish hepatocytes, which retain many of the native properties of the liver, has been proposed for in vitro screening of estrogen receptor (ER) agonists and antagonists. The aim of present study was to characterize the molecular mode of action (MoA) of the ER agonist 17α-ethinylestradiol (EE2) in primary rainbow trout (Oncorhynchus mykiss) hepatocytes. A custom designed salmonid 60,000-feature (60k) oligonucleotide microarray was used to characterize the potential MoAs after 48h exposure to EE2. The microarray analysis revealed several concentration-dependent gene expression alterations including classical estrogen sensitive biomarker gene expression (e.g. estrogen receptor α, vitellogenin, zona radiata). Gene Ontology (GO) analysis displayed transcriptional changes suggesting interference of cellular growth, fatty acid and lipid metabolism potentially mediated through the estrogen receptor (ER), which were proposed to be associated with modulation of genes involved in endocrine function and reproduction. Pathway analysis supported the identified GOs and revealed modulation of additional genes associated with apoptosis and cholesterol biosynthesis. Differentially expressed genes (DEGs) related to impaired lipid metabolism (e.g. peroxisome proliferator-activated receptor α and γ), growth (e.g. insulin growth factor protein 1), phase I and II biotransformation (e.g. cytochrome P450 1A, sulfotransferase, UDP-glucuronosyltransferase and glutathione S-transferase) provided additional

  19. Global Gene Expression Analysis in PKCα-/- Mouse Skin Reveals Structural Changes in the Dermis and Defective Wound Granulation Tissue.

    PubMed

    Cooper, Nichola H; Balachandra, Jeya P; Hardman, Matthew J

    2015-12-01

    The skin's mechanical integrity is maintained by an organized and robust dermal extracellular matrix (ECM). Resistance to mechanical disruption hinges primarily on homeostasis of the dermal collagen fibril architecture, which is regulated, at least in part, by members of the small leucine-rich proteoglycan (SLRP) family. Here we present data linking protein kinase C alpha (PKCα) to the regulated expression of multiple ECM components including SLRPs. Global microarray profiling reveals deficiencies in ECM gene expression in PKCα-/- skin correlating with abnormal collagen fibril morphology, disorganized dermal architecture, and reduced skin strength. Detailed analysis of the skin and wounds from wild-type and PKCα-/- mice reveals a failure to upregulate collagen and other ECM components in response to injury, resulting in delayed granulation tissue deposition in PKCα-/- wounds. Thus, our data reveal a previously unappreciated role for PKCα in the regulation of ECM structure and deposition during skin wound healing.

  20. Systematic Global Analysis of Genes Encoding Protein Phosphatases in Aspergillus fumigatus

    PubMed Central

    Winkelströter, Lizziane K.; Dolan, Stephen K.; Fernanda dos Reis, Thaila; Bom, Vinícius Leite Pedro; Alves de Castro, Patrícia; Hagiwara, Daisuke; Alowni, Raneem; Jones, Gary W.; Doyle, Sean; Brown, Neil Andrew; Goldman, Gustavo H.

    2015-01-01

    Aspergillus fumigatus is a fungal pathogen that causes several invasive and noninvasive diseases named aspergillosis. This disease is generally regarded as multifactorial, considering that several pathogenicity determinants are present during the establishment of this illness. It is necessary to obtain an increased knowledge of how, and which, A. fumigatus signal transduction pathways are engaged in the regulation of these processes. Protein phosphatases are essential to several signal transduction pathways. We identified 32 phosphatase catalytic subunit-encoding genes in A. fumigatus, of which we were able to construct 24 viable deletion mutants. The role of nine phosphatase mutants in the HOG (high osmolarity glycerol response) pathway was evaluated by measuring phosphorylation of the p38 MAPK (SakA) and expression of osmo-dependent genes. We were also able to identify 11 phosphatases involved in iron assimilation, six that are related to gliotoxin resistance, and three implicated in gliotoxin production. These results present the creation of a fundamental resource for the study of signaling in A. fumigatus and its implications in the regulation of pathogenicity determinants and virulence in this important pathogen. PMID:25943523

  1. Global Gene Expression of Kosteletzkya virginica Seedlings Responding to Salt Stress

    PubMed Central

    Tang, Xiaoli; Wang, Hongyan; Shao, Chuyang; Shao, Hongbo

    2015-01-01

    Soil salinization is becoming a serious threat to crop yield all over the world. Nowadays, acquainting the specific molecular mechanisms underlying various abiotic stresses especially to salt stress should be of great importance. While the development of the high-throughout sequencing technology promoted the progress powerfully. The intricate perception, transduction and regulation mechanisms underlying salt stress are being illustrated more and more clearly. As a perennial halophytic plant, Kosteletzkya virginica is able to help us to understand the mechanisms more directly and effectively. We carried out the whole transcriptome analysis on young seedlings with or without salt treatment through high-throughout sequencing technology. The results revealed that the numbers of different expressed transcripts between control and different treatments are 4145 and 9134, respectively. The ORF prediction suggested that there were 94308 ORF out of the 103489 (91.10%) total transcripts. We also carried out further differential expression analysis through gene ontology (GO) classification, cluster of orthologous groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In a word, our transcriptome study on Kosteletzkya virginica would provide direct and effective references for researches on molecular mechanisms of salt-tolerance, extending our view of salt tolerance in plant further. Above all, the related report in this paper is the first about Kosteletzkya virginica. PMID:25901608

  2. Role of Corynebacterium glutamicum sprA Encoding a Serine Protease in glxR-Mediated Global Gene Regulation

    PubMed Central

    Hong, Eun-Ji; Park, Joon-Song; Kim, Younhee; Lee, Heung-Shick

    2014-01-01

    The global regulator glxR of Corynebacterium glutamicum is involved in many cellular activities. Considering its role, the GlxR protein likely interacts with other proteins to obtain, maintain, and control its activity. To isolate proteins interacting with GlxR, we used a two-hybrid system with GlxR as the bait. Subsequently, the partner, a subtilisin-like serine protease, was isolated from a C. glutamicum genomic library. Unlike glxR, which showed constitutive expression, the expression of sprA, encoding a serine protease, was maximal in the log phase. Purified His6-SprA protein underwent self-proteolysis and proteolyzed purified GlxR. The proteolytic action of SprA on GlxR was not observed in the presence of cyclic adenosine monophosphate, which modulates GlxR activity. The C. glutamicum sprA deletion mutant (ΔsprA) and sprA-overexpressing (P180-sprA) strains showed reduced growth. The activity of isocitrate dehydrogenase (a tricarboxylic acid cycle enzyme) in these strains decreased to 30–50% of that in the wild-type strain. In the P180-sprA strain, proteins involved in diverse cellular functions such as energy and carbon metabolism (NCgl2809), nitrogen metabolism (NCgl0049), methylation reactions (NCgl0719), and peptidoglycan biosynthesis (NCgl1267), as well as stress, starvation, and survival (NCgl0938) were affected and showed decreased transcription. Taken together, these data suggest that SprA, as a serine protease, performs a novel regulatory role not only in glxR-mediated gene expression but also in other areas of cell physiology. In addition, the tight control of SprA and GlxR availability may indicate their importance in global gene regulation. PMID:24691519

  3. Genome-wide Annotation, Identification, and Global Transcriptomic Analysis of Regulatory or Small RNA Gene Expression in Staphylococcus aureus

    PubMed Central

    Weiss, Andy; Broach, William H.; Wiemels, Richard E.; Mogen, Austin B.; Rice, Kelly C.

    2016-01-01

    ABSTRACT In Staphylococcus aureus, hundreds of small regulatory or small RNAs (sRNAs) have been identified, yet this class of molecule remains poorly understood and severely understudied. sRNA genes are typically absent from genome annotation files, and as a consequence, their existence is often overlooked, particularly in global transcriptomic studies. To facilitate improved detection and analysis of sRNAs in S. aureus, we generated updated GenBank files for three commonly used S. aureus strains (MRSA252, NCTC 8325, and USA300), in which we added annotations for >260 previously identified sRNAs. These files, the first to include genome-wide annotation of sRNAs in S. aureus, were then used as a foundation to identify novel sRNAs in the community-associated methicillin-resistant strain USA300. This analysis led to the discovery of 39 previously unidentified sRNAs. Investigating the genomic loci of the newly identified sRNAs revealed a surprising degree of inconsistency in genome annotation in S. aureus, which may be hindering the analysis and functional exploration of these elements. Finally, using our newly created annotation files as a reference, we perform a global analysis of sRNA gene expression in S. aureus and demonstrate that the newly identified tsr25 is the most highly upregulated sRNA in human serum. This study provides an invaluable resource to the S. aureus research community in the form of our newly generated annotation files, while at the same time presenting the first examination of differential sRNA expression in pathophysiologically relevant conditions. PMID:26861020

  4. Mining drill

    SciTech Connect

    Sarin, V.K.

    1983-08-16

    In a mine tool of the type having a drive body holding a bit, the drive body includes a pair of forwardly projecting flanges forming air passages in proximity to the cutting edges for the convey of detritus.

  5. Global gene expression analysis of glucose overflow metabolism in Escherichia coli and reduction of aerobic acetate formation.

    PubMed

    Veit, Andrea; Polen, Tino; Wendisch, Volker F

    2007-02-01

    During aerobic growth on glucose, Escherichia coli produces acetate in the so-called overflow metabolism. DNA microarray analysis was used to determine the global gene expression patterns of chemostat cultivations of E. coli MG1655 that were characterized by different acetate formation rates during aerobic growth on glucose. A correlation analysis identified that expression of ten genes (sdhCDAB, sucB, sucC, acnB, lpdA, fumC and mdh) encoding the TCA cycle enzymes succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinyl-CoA synthetase, aconitase, fumarase and malate dehydrogenase, respectively, and of the acs-yjcH-actP operon for acetate utilization correlated negatively with acetate formation. Relieving transcriptional control of the sdhCDAB-b0725-sucABCD operon by chromosomal promoter exchange mutagenesis yielded a strain with increased specific activities of the TCA cycle enzymes succinate dehydrogenase, alpha-ketoglutarate dehydrogenase and succinyl-CoA synthetase, which are encoded by this operon. The resulting strain produced less acetate and directed more carbon towards carbon dioxide formation than the parent strain MG1655 while maintaining high growth and glucose consumption rates. PMID:17273855

  6. RNA sequencing of an nsdC mutant reveals global regulation of secondary metabolic gene clusters in Aspergillus flavus.

    PubMed

    Gilbert, Matthew K; Mack, Brian M; Wei, Qijian; Bland, John M; Bhatnagar, Deepak; Cary, Jeffrey W

    2016-01-01

    The filamentous fungus, Aspergillus flavus (A. flavus) is an opportunistic pathogen capable of invading a number of crops and contaminating them with toxic secondary metabolites such as aflatoxins. Characterizing the molecular mechanisms governing growth and development of this organism is vital for developing safe and effective strategies for reducing crop contamination. The transcription factor nsdC has been identified as being required for normal asexual development and aflatoxin production in A. flavus. Building on a previous study using a large (L)-sclerotial morphotype A. flavus nsdC mutant we observed alterations in conidiophore development and loss of sclerotial and aflatoxin production using a nsdC mutant of a small (S)-sclerotial morphotype, that normally produces aflatoxin and sclerotia in quantities much higher than the L-morphotype. RNA sequencing analysis of the nsdC knockout mutant and isogenic control strain identified a number of differentially expressed genes related to development and production of secondary metabolites, including aflatoxin, penicillin and aflatrem. Further, RNA-seq data indicating down regulation of aflatrem biosynthetic gene expression in the nsdC mutant correlated with HPLC analyses showing a decrease in aflatrem levels. The current study expands the role of nsdC as a globally acting transcription factor that is a critical regulator of both asexual reproduction and secondary metabolism in A. flavus. PMID:26686623

  7. Transcription-coupled and global genome repair in the Saccharomyces cerevisiae RPB2 gene at nucleotide resolution.

    PubMed Central

    Tijsterman, M; Tasseron-de Jong, J G; van de Putte, P; Brouwer, J

    1996-01-01

    Repair of UV-induced cyclobutane pyrimidine dimers (CPDs) was examined at single nucleotide resolution in the yeast Saccharomyces cerevisiae, using an improved protocol for genomic end-labelling. To obtain the sensitivity required for adduct detection in yeast, an oligonucleotide-directed enrichment step was introduced into the current methodology developed for adduct detection in Escherichia coli. With this method, heterogeneous repair of CPDs within the RPB2 locus is observed. Individual CPDs positioned in the transcribed strand are removed very efficiently with identical kinetics. This fast repair starts within 23 bases downstream of the transcription initiation site. The non-transcribed strand of the active gene exhibits slow repair without detectable repair variations between individual lesions. In contrast, CPDs positioned in the promoter region show profound repair heterogeneity. Here, CPDs at specific sites are removed very quickly, with comparable rates to CPDs positioned in the transcribed strand, while at other positions lesions are not repaired at all during the period studied. Interestingly, the fast repair in the promoter region is dependent on the RAD7 and RAD16 genes, as are the slowly repaired CPDs in this region and in the non-transcribed strand. This indicates that the global genome repair pathway is not intrinsically slow and at specific positions can be as efficient as the transcription-coupled repair pathway. PMID:8836174

  8. Dietary choline deficiency alters global and gene-specific DNA methylation in the developing hippocampus of mouse fetal brains.

    PubMed

    Niculescu, Mihai D; Craciunescu, Corneliu N; Zeisel, Steven H

    2006-01-01

    The availability of choline during critical periods of fetal development alters hippocampal development and affects memory function throughout life. Choline deficiency during fetal development reduces proliferation and migration of neuronal precursor cells in the mouse fetal hippocampus and these changes are associated with modifications in the protein levels of some cell cycle regulators and early differentiation markers. We fed C57 BL/6 mouse dams diets deficient or normal in choline content from days 12 to 17 of pregnancy, and then collected fetal brains on embryonic day 17. Using laser-capture micro-dissection we harvested cells from the ventricular and subventricular zones of Ammon's horn and from the prime germinal zone of the dentate gyrus (hippocampus). In the ventricular and subventricular zones from the choline-deficient group, we observed increased protein levels for kinase-associated phosphatase (Kap) and for p15(INK4b) (two cell cycle inhibitors). In the dentate gyrus, we observed increased levels of calretinin (an early marker of neuronal differentiation). In fetal brain from mothers fed a choline-deficient diet, DNA global methylation was decreased in the ventricular and subventricular zones of Ammon's horn. We also observed decreased gene-specific DNA methylation of the gene (Cdkn3) that encodes for Kap, correlating with increased expression of this protein. This was not the case for p15(INK4b) or calretinin (Cdkn2b and Calb2, respectively). These data suggest that choline deficiency-induced changes in gene methylation could mediate the expression of a cell cycle regulator and thereby alter brain development.

  9. RNA Sequencing of Formalin-Fixed, Paraffin-Embedded Specimens for Gene Expression Quantification and Data Mining

    PubMed Central

    Wu, Jie; Ye, Fei; Su, Yinghao; Clark, Travis; Shu, Xiao-ou

    2016-01-01

    Background. Proper rRNA depletion is crucial for the successful utilization of FFPE specimens when studying gene expression. We performed a study to evaluate two major rRNA depletion methods: Ribo-Zero and RNase H. RNAs extracted from 4 samples were treated with the two rRNA depletion methods in duplicate and sequenced (N = 16). We evaluated their reducibility, ability to detect RNA, and ability to molecularly subtype these triple negative breast cancer specimens. Results. Both rRNA depletion methods produced consistent data between the technical replicates. We found that the RNase H method produced higher quality RNAseq data as compared to the Ribo-Zero method. In addition, we evaluated the RNAseq data generated from the FFPE tissue samples for noncoding RNA, including lncRNA, enhancer/super enhancer RNA, and single nucleotide variation (SNV). We found that the RNase H is more suitable for detecting high-quality, noncoding RNAs as compared to the Ribo-Zero and provided more consistent molecular subtype identification between replicates. Unfortunately, neither method produced reliable SNV data. Conclusions. In conclusion, for FFPE specimens, the RNase H rRNA depletion method performed better than the Ribo-Zero. Neither method generates data sufficient for SNV detection. PMID:27774452

  10. Global mapping of herpesvirus-host protein complexes reveals a novel transcription strategy for late genes

    PubMed Central

    Davis, Zoe H.; Verschueren, Erik; Jang, Gwendolyn M.; Kleffman, Kevin; Johnson, Jeffrey R.; Park, Jimin; Von Dollen, John; Maher, M. Cyrus; Johnson, Tasha; Newton, William; Jäger, Stefanie; Shales, Michael; Horner, Julie; Hernandez, Ryan D.; Krogan, Nevan J.; Glaunsinger, Britt A.

    2014-01-01

    SUMMARY Mapping host-pathogen interactions has proven instrumental for understanding how viruses manipulate host machinery and how numerous cellular processes are regulated. DNA viruses such as herpesviruses have relatively large coding capacity and thus can target an extensive network of cellular proteins. To identify the host proteins hijacked by this pathogen, we systematically affinity tagged and purified all 89 proteins of Kaposi’s sarcoma-associated herpesvirus (KSHV) from human cells. Mass spectrometry of this material identified over 500 virus-host interactions. KSHV causes AIDS-associated cancers and its interaction network is enriched for proteins linked to cancer and overlaps with proteins that are also targeted by HIV-1. We found that the conserved KSHV protein ORF24 binds to RNA polymerase II and brings it to viral late promoters by mimicking and replacing cellular TATA-box-binding protein (TBP). This is required for herpesviral late gene expression, a complex and poorly understood phase of the viral lifecycle. PMID:25544563

  11. Global gene expression analysis using RNA-seq uncovered a new role for SR1/CAMTA3 transcription factor in salt stress.

    PubMed

    Prasad, Kasavajhala V S K; Abdel-Hameed, Amira A E; Xing, Denghui; Reddy, Anireddy S N

    2016-01-01

    Abiotic and biotic stresses cause significant yield losses in all crops. Acquisition of stress tolerance in plants requires rapid reprogramming of gene expression. SR1/CAMTA3, a member of signal responsive transcription factors (TFs), functions both as a positive and a negative regulator of biotic stress responses and as a positive regulator of cold stress-induced gene expression. Using high throughput RNA-seq, we identified ~3000 SR1-regulated genes. Promoters of about 60% of the differentially expressed genes have a known DNA binding site for SR1, suggesting that they are likely direct targets. Gene ontology analysis of SR1-regulated genes confirmed previously known functions of SR1 and uncovered a potential role for this TF in salt stress. Our results showed that SR1 mutant is more tolerant to salt stress than the wild type and complemented line. Improved tolerance of sr1 seedlings to salt is accompanied with the induction of salt-responsive genes. Furthermore, ChIP-PCR results showed that SR1 binds to promoters of several salt-responsive genes. These results suggest that SR1 acts as a negative regulator of salt tolerance by directly repressing the expression of salt-responsive genes. Overall, this study identified SR1-regulated genes globally and uncovered a previously uncharacterized role for SR1 in salt stress response. PMID:27251464

  12. Global gene expression analysis using RNA-seq uncovered a new role for SR1/CAMTA3 transcription factor in salt stress

    PubMed Central

    Prasad, Kasavajhala V. S. K.; Abdel-Hameed, Amira A. E.; Xing, Denghui; Reddy, Anireddy S. N.

    2016-01-01

    Abiotic and biotic stresses cause significant yield losses in all crops. Acquisition of stress tolerance in plants requires rapid reprogramming of gene expression. SR1/CAMTA3, a member of signal responsive transcription factors (TFs), functions both as a positive and a negative regulator of biotic stress responses and as a positive regulator of cold stress-induced gene expression. Using high throughput RNA-seq, we identified ~3000 SR1-regulated genes. Promoters of about 60% of the differentially expressed genes have a known DNA binding site for SR1, suggesting that they are likely direct targets. Gene ontology analysis of SR1-regulated genes confirmed previously known functions of SR1 and uncovered a potential role for this TF in salt stress. Our results showed that SR1 mutant is more tolerant to salt stress than the wild type and complemented line. Improved tolerance of sr1 seedlings to salt is accompanied with the induction of salt-responsive genes. Furthermore, ChIP-PCR results showed that SR1 binds to promoters of several salt-responsive genes. These results suggest that SR1 acts as a negative regulator of salt tolerance by directly repressing the expression of salt-responsive genes. Overall, this study identified SR1-regulated genes globally and uncovered a previously uncharacterized role for SR1 in salt stress response. PMID:27251464

  13. Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease

    PubMed Central

    Yoshihara, Daisuke; Kugita, Masanori; Yamaguchi, Tamio; Aukema, Harold M.; Kurahashi, Hiroki; Morita, Miwa; Hiki, Yoshiyuki; Calvet, James P.; Wallace, Darren P.; Toyohara, Takafumi; Abe, Takaaki; Nagao, Shizuko

    2012-01-01

    Kidneys are enlarged by aberrant proliferation of tubule epithelial cells leading to the formation of numerous cysts, nephron loss, and interstitial fibrosis in polycystic kidney disease (PKD). Pioglitazone (PIO), a PPAR-γ agonist, decreased cell proliferation, interstitial fibrosis, and inflammation, and ameliorated PKD progression in PCK rats (Am. J. Physiol.-Renal, 2011). To explore genetic mechanisms involved, changes in global gene expression were analyzed. By Gene Set Enrichment Analysis of 30655 genes, 13 of the top 20 downregulated gene ontology biological process gene sets and six of the top 20 curated gene set canonical pathways identified to be downregulated by PIOtreatment were related to cell cycle and proliferation, including EGF, PDGF and JNK pathways. Their relevant pathways were identified using the Kyoto Encyclopedia of Gene and Genomes database. Stearoyl-coenzyme A desaturase 1 is a key enzyme in fatty acid metabolism found in the top 5 genes downregulated by PIO treatment. Immunohistochemical analysis revealed that the gene product of this enzyme was highly expressed in PCK kidneys and decreased by PIO. These data show that PIO alters the expression of genes involved in cell cycle progression, cell proliferation, and fatty acid metabolism. PMID:22666229

  14. Characterization of Timed Changes in Hepatic Copper Concentrations, Methionine Metabolism, Gene Expression, and Global DNA Methylation in the Jackson Toxic Milk Mouse Model of Wilson Disease

    PubMed Central

    Le, Anh; Shibata, Noreene M.; French, Samuel W.; Kim, Kyoungmi; Kharbanda, Kusum K.; Islam, Mohammad S.; LaSalle, Janine M.; Halsted, Charles H.; Keen, Carl L.; Medici, Valentina

    2014-01-01

    Background Wilson disease (WD) is characterized by hepatic copper accumulation with progressive liver damage to cirrhosis. This study aimed to characterize the toxic milk mouse from The Jackson Laboratory (Bar Harbor, ME, USA) (tx-j) mouse model of WD according to changes over time in hepatic copper concentrations, methionine metabolism, global DNA methylation, and gene expression from gestational day 17 (fetal) to adulthood (28 weeks). Methods Included liver histology and relevant biochemical analyses including hepatic copper quantification, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) liver levels, qPCR for transcript levels of genes relevant to methionine metabolism and liver damage, and DNA dot blot for global DNA methylation. Results Hepatic copper was lower in tx-j fetuses but higher in weanling (three weeks) and adult tx-j mice compared to controls. S-adenosylhomocysteinase transcript levels were significantly lower at all time points, except at three weeks, correlating negatively with copper levels and with consequent changes in the SAM:SAH methylation ratio and global DNA methylation. Conclusion Compared to controls, methionine metabolism including S-adenosylhomocysteinase gene expression is persistently different in the tx-j mice with consequent alterations in global DNA methylation in more advanced stages of liver disease. The inhibitory effect of copper accumulation on S-adenosylhomocysteinase expression is associated with progressively abnormal methionine metabolism and decreased methylation capacity and DNA global methylation. PMID:24810691

  15. Evolution of Bacillus subtilis to enhanced hypobaric growth: global alterations in gene expression

    NASA Astrophysics Data System (ADS)

    Nicholson, Wayne; Robles-Martinez, Jose; Rivas-Castillo, Andrea; Schuerger, Andrew

    selective antibiotics at 27C with shaking in Earth atmosphere at a pressure of 1013 mbar (1 atm; WN628) or at 50 mbar (WN624). At 24-hour (˜6.6 generation) intervals, culture optical densities at 660 nm (OD660) were recorded, cultures diluted 1:100 into fresh selective medium, and propagation continued. After 1,000 generations of propagation, single-colony isolates were obtained from each culture and designated WN1105 (evolved at 1013 mbar) and WN1106 (evolved at 50 mbar), respectively. Propagation of both strains WN628 or WN624 at 1013 or 50 mbar for 1,000 generations resulted in an overall increase in 24-hour OD660 values. Increases were seen to occur in a stepwise fashion, suggesting that evolution of the strains was accomplished via a sequence of mutational events and population sweeps [6]. Both evolved strains WN1105 and WN1106 had gained fitness relative to their wild-type ancestors when competition experiments were performed at the original pressure at which the respective strains had evolved. As might be expected, strain WN1106 was more fit at 50 mbar than WN1105, and WN1105 was more fit than WN1106 at 1013 mbar. Interestingly, strain WN1105 was less fit than the ancestor at 50 mbar, whereas WN1106 showed the same fitness at its ancestral strain at 1013 mbar. Transcription microarrays were performed on the ancestral WN624 and low-pressure evolved WN1106 strains grown at 1013 mbar or 50 mbar. A number of genes were identified as tran-scriptionally induced (i) in both ancestral and evolved strain at 50 mbar and (ii) preferentially induced in the evolved strain at 50 mbar. The genes involved belong to at least 3 distinct stress-induced regulons. References: [1] Nicholson, W.L. (2009) Trends Microbiol, 17, 243-250. [2] Nicholson, W.L., et al. (2009) Trends in Microbiol, 17, 389-392. [3] Nicholson W.L., et al. (2000) Microbiol. Molec. Biol. Rev, 64, 548-572. [4] Fajardo-Cavazos, P. et al. (2006) Acta Astronautica, 60, 534-540. [5] Schuerger, A.C. and Nicholson, W

  16. Evolution of Bacillus subtilis to enhanced hypobaric growth: global alterations in gene expression

    NASA Astrophysics Data System (ADS)

    Nicholson, Wayne; Robles-Martinez, Jose; Rivas-Castillo, Andrea; Schuerger, Andrew

    selective antibiotics at 27C with shaking in Earth atmosphere at a pressure of 1013 mbar (1 atm; WN628) or at 50 mbar (WN624). At 24-hour (˜6.6 generation) intervals, culture optical densities at 660 nm (OD660) were recorded, cultures diluted 1:100 into fresh selective medium, and propagation continued. After 1,000 generations of propagation, single-colony isolates were obtained from each culture and designated WN1105 (evolved at 1013 mbar) and WN1106 (evolved at 50 mbar), respectively. Propagation of both strains WN628 or WN624 at 1013 or 50 mbar for 1,000 generations resulted in an overall increase in 24-hour OD660 values. Increases were seen to occur in a stepwise fashion, suggesting that evolution of the strains was accomplished via a sequence of mutational events and population sweeps [6]. Both evolved strains WN1105 and WN1106 had gained fitness relative to their wild-type ancestors when competition experiments were performed at the original pressure at which the respective strains had evolved. As might be expected, strain WN1106 was more fit at 50 mbar than WN1105, and WN1105 was more fit than WN1106 at 1013 mbar. Interestingly, strain WN1105 was less fit than the ancestor at 50 mbar, whereas WN1106 showed the same fitness at its ancestral strain at 1013 mbar. Transcription microarrays were performed on the ancestral WN624 and low-pressure evolved WN1106 strains grown at 1013 mbar or 50 mbar. A number of genes were identified as tran-scriptionally induced (i) in both ancestral and evolved strain at 50 mbar and (ii) preferentially induced in the evolved strain at 50 mbar. The genes involved belong to at least 3 distinct stress-induced regulons. References: [1] Nicholson, W.L. (2009) Trends Microbiol, 17, 243-250. [2] Nicholson, W.L., et al. (2009) Trends in Microbiol, 17, 389-392. [3] Nicholson W.L., et al. (2000) Microbiol. Molec. Biol. Rev, 64, 548-572. [4] Fajardo-Cavazos, P. et al. (2006) Acta Astronautica, 60, 534-540. [5] Schuerger, A.C. and Nicholson, W

  17. Cigarette smoke-induced emphysema in A/J mice is associated with pulmonary oxidative stress, apoptosis of lung cells, and global alterations in gene expression

    PubMed Central

    Rangasamy, Tirumalai; Misra, Vikas; Zhen, Lijie; Tankersley, Clarke G.; Tuder, Rubin M.; Biswal, Shyam

    2009-01-01

    Cigarette smoking is the major risk factor for developing chronic obstructive pulmonary disease, the fourth leading cause of deaths in the United States. Despite recent advances, the molecular mechanisms involved in the initiation and progression of this disease remain elusive. We used Affymetrix Gene Chip arrays to determine the temporal alterations in global gene expression during the progression of pulmonary emphysema in A/J mice. Chronic cigarette smoke (CS) exposure caused pulmonary emphysema in A/J mice, which was associated with pronounced bronchoalveolar inflammation, enhanced oxidative stress, and increased apoptosis of alveolar septal cells. Microarray analysis revealed the upregulation of 1,190, 715, 260, and 246 genes and the downregulation of 1,840, 730, 442, and 236 genes in the lungs of mice exposed to CS for 5 h, 8 days, and 1.5 and 6 mo, respectively. Most of the genes belong to the functional categories of phase I genes, Nrf2-regulated antioxidant and phase II genes, phase III detoxification genes, and others including immune/inflammatory response genes. Induction of the genes encoding multiple phase I enzymes was markedly higher in the emphysematous lungs, whereas reduced expression of various cytoprotective genes constituting ubiquitin-proteasome complex, cell survival pathways, solute carriers and transporters, transcription factors, and Nrf2-regulated antioxidant and phase II-responsive genes was noted. Our data indicate that the progression of CS-induced emphysema is associated with a steady decline in the expression of various genes involved in multiple pathways in the lungs of A/J mice. Many of the genes discovered in this study could rationally play an important role in the susceptibility to CS-induced emphysema. PMID:19286929

  18. Coastal mining

    NASA Astrophysics Data System (ADS)

    Bell, Peter M.

    The Exclusive Economic Zone (EEZ) declared by President Reagan in March 1983 has met with a mixed response from those who would benefit from a guaranteed, 200-nautical-mile (370-km) protected underwater mining zone off the coasts of the United States and its possessions. On the one hand, the U.S. Department of the Interior is looking ahead and has been very successful in safeguarding important natural resources that will be needed in the coming decades. On the other hand, the mining industry is faced with a depressed metals and mining market.A report of the Exclusive Economic Zone Symposium held in November 1983 by the U.S. Geological Survey, the Mineral Management Service, and the Bureau of Mines described the mixed response as: “ … The Department of Interior … raring to go into promotion of deep-seal mining but industrial consortia being very pessimistic about the program, at least for the next 30 or so years.” (Chemical & Engineering News, February 5, 1983).

  19. Mining with backfill

    SciTech Connect

    Granholm, S.

    1983-01-01

    This book reviews the fill mining practice in Sweden and other countries. Research results and technological innovations are presented on mining methods, mining operations, mining machinery and geomechanics. Other topics discussed are fill properties, technology, geomechanics, and new development.

  20. Asteroid mining

    NASA Technical Reports Server (NTRS)

    Gertsch, Richard E.

    1992-01-01

    The earliest studies of asteroid mining proposed retrieving a main belt asteroid. Because of the very long travel times to the main asteroid belt, attention has shifted to the asteroids whose orbits bring them fairly close to the Earth. In these schemes, the asteroids would be bagged and then processed during the return trip, with the asteroid itself providing the reaction mass to propel the mission homeward. A mission to one of these near-Earth asteroids would be shorter, involve less weight, and require a somewhat lower change in velocity. Since these asteroids apparently contain a wide range of potentially useful materials, our study group considered only them. The topics covered include asteroid materials and properties, asteroid mission selection, manned versus automated missions, mining in zero gravity, and a conceptual mining method.

  1. Comparative analysis of global gene expression profiles between diabetic rat wounds treated with vacuum-assisted closure therapy, moist wound healing or gauze under suction.

    PubMed

    Derrick, Kathleen L; Norbury, Kenneth; Kieswetter, Kris; Skaf, Jihad; McNulty, Amy K

    2008-12-01

    How differential gene expression affects wound healing is not well understood. In this study, Zucker diabetic fatty (fa/fa) male inbred rats were used to investigate gene expression during wound healing in an impaired wound-healing model. Whole genome microarray surveys were used to gain insight into the biological pathways and healing processes in acute excisional wounds treated with vacuum-assisted closure (V.A.C.). Therapy, moist wound healing (MWH) or gauze under suction (GUS). Global gene expression analyses after 2 days of healing indicated major differences with respect to both number of genes showing fold changes and pathway regulation between the three different wound treatments. Statistical analysis of expression profiles indicated that 5072 genes showed a >1.6-fold change with V.A.C. Therapy compared with 3601 genes with MWH and 3952 genes with GUS. Pathways and related genes associated with the early phases of wound healing diverged between treatment groups. For example, pathways involving angiogenesis, cytoskeletal regulation and inflammation were associated with elevated gene expression following V.A.C. Therapy. This study is the first to assess wound healing by whole genome interrogation in a diabetic rat model treated with different healing modalities.

  2. Case study on the utility of hepatic global gene expression profiling in the risk assessment of the carcinogen furan

    SciTech Connect

    Jackson, Anna Francina; Williams, Andrew; Recio, Leslie; Waters, Michael D.; Lambert, Iain B.; Yauk, Carole L.

    2014-01-01

    Furan is a chemical hepatocarcinogen in mice and rats. Its previously postulated cancer mode of action (MOA) is chronic cytotoxicity followed by sustained regenerative proliferation; however, its molecular basis is unknown. To this end, we conducted toxicogenomic analysis of B3C6F1 mouse livers following three week exposures to non-carcinogenic (0, 1, 2 mg/kg bw) or carcinogenic (4 and 8 mg/kg bw) doses of furan. We saw enrichment for pathways responsible for cytotoxicity: stress-activated protein kinase (SAPK) and death receptor (DR5 and TNF-alpha) signaling, and proliferation: extracellular signal-regulated kinases (ERKs) and TNF-alpha. We also noted the involvement of NF-kappaB and c-Jun in response to furan, which are genes that are known to be required for liver regeneration. Furan metabolism by CYP2E1 produces cis-2-butene-1,4-dial (BDA), which is required for ensuing cytotoxicity and oxidative stress. NRF2 is a master regulator of gene expression during oxidative stress and we suggest that chronic NFR2 activity and chronic inflammation may represent critical transition events between the adaptive (regeneration) and adverse (cancer) outcomes. Another objective of this study was to demonstrate the applicability of toxicogenomics data in quantitative risk assessment. We modeled benchmark doses for our transcriptional data and previously published cancer data, and observed consistency between the two. Margin of exposure values for both transcriptional and cancer endpoints were also similar. In conclusion, using furan as a case study we have demonstrated the value of toxicogenomics data in elucidating dose-dependent MOA transitions and in quantitative risk assessment. - Highlights: • Global gene expression changes in furan-exposed mouse livers were analyzed. • A molecular mode of action for furan-induced hepatocarcinogenesis is proposed. • Key pathways include NRF2, SAPK, ERK and death receptor signaling. • Important roles for TNF-alpha, c-Jun, and NF

  3. A factor analysis of global GABAergic gene expression in human brain identifies specificity in response to chronic alcohol and cocaine exposure.

    PubMed

    Enoch, Mary-Anne; Baghal, Basel; Yuan, Qiaoping; Goldman, David

    2013-01-01

    Although expression patterns of GABAergic genes in rodent brain have largely been elucidated, no comprehensive studies have been performed in human brain. The purpose of this study was to identify global patterns of GABAergic gene expression in healthy adults, including trans and cis effects in the GABAA gene clusters, before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA-Seq data from 'BrainSpan' was obtained across 16 brain regions from postmortem samples from nine adults. A factor analysis was performed on global expression of 21 GABAergic pathway genes. Factor specificity for response to chronic alcohol/cocaine exposure was subsequently determined from the analysis of RNA-Seq data from postmortem hippocampus of eight alcoholics, eight cocaine addicts and eight controls. Six gene expression factors were identified. Most genes loaded (≥0.5) onto one factor; six genes loaded onto two. The largest factor (0.30 variance) included the chromosome 5 gene cluster that encodes the most common GABAA receptor, α1β2γ2, and genes encoding the α3β3γ2 receptor. Genes within this factor were largely unresponsive to chronic alcohol/cocaine exposure. In contrast, the chromosome 4 gene cluster factor (0.14 variance) encoding the α2β1γ1 receptor was influenced by chronic alcohol/cocaine exposure. Two other factors (0.17 and 0.06 variance) showed expression changes in alcoholics/cocaine addicts; these factors included genes involved in GABA synthesis and synaptic transport. Finally there were two factors that included genes with exceptionally low (0.10 variance) and high (0.09 variance) expression in the cerebellum; the former factor was unaffected by alcohol/cocaine exposure. This study has shown that there appears to be specificity of GABAergic gene groups, defined by covariation in expression, for response to chronic alcohol/cocaine exposure. These findings might have implications for combating stress

  4. A Factor Analysis of Global GABAergic Gene Expression in Human Brain Identifies Specificity in Response to Chronic Alcohol and Cocaine Exposure

    PubMed Central

    Yuan, Qiaoping; Goldman, David

    2013-01-01

    Although expression patterns of GABAergic genes in rodent brain have largely been elucidated, no comprehensive studies have been performed in human brain. The purpose of this study was to identify global patterns of GABAergic gene expression in healthy adults, including trans and cis effects in the GABAA gene clusters, before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA-Seq data from ‘BrainSpan’ was obtained across 16 brain regions from postmortem samples from nine adults. A factor analysis was performed on global expression of 21 GABAergic pathway genes. Factor specificity for response to chronic alcohol/cocaine exposure was subsequently determined from the analysis of RNA-Seq data from postmortem hippocampus of eight alcoholics, eight cocaine addicts and eight controls. Six gene expression factors were identified. Most genes loaded (≥0.5) onto one factor; six genes loaded onto two. The largest factor (0.30 variance) included the chromosome 5 gene cluster that encodes the most common GABAA receptor, α1β2γ2, and genes encoding the α3β3γ2 receptor. Genes within this factor were largely unresponsive to chronic alcohol/cocaine exposure. In contrast, the chromosome 4 gene cluster factor (0.14 variance) encoding the α2β1γ1 receptor was influenced by chronic alcohol/cocaine exposure. Two other factors (0.17 and 0.06 variance) showed expression changes in alcoholics/cocaine addicts; these factors included genes involved in GABA synthesis and synaptic transport. Finally there were two factors that included genes with exceptionally low (0.10 variance) and high (0.09 variance) expression in the cerebellum; the former factor was unaffected by alcohol/cocaine exposure. This study has shown that there appears to be specificity of GABAergic gene groups, defined by covariation in expression, for response to chronic alcohol/cocaine exposure. These findings might have implications for combating stress

  5. Globally dispersed mobile drug-resistance genes in Gram-negative bacterial isolates from patients with bloodstream infections in a US urban general hospital

    PubMed Central

    Adams-Sapper, S.; Sergeevna-Selezneva, J.; Tartof, S.; Raphael, E.; Diep, B. An; Perdreau-Remington, F.

    2012-01-01

    Mobile drug-resistance genes with identical nucleic acid sequences carried by multidrug-resistant Escherichia coli strains that cause community-acquired infections are becomingly increasingly dispersed worldwide. Over a 2-year period, we analysed Gram-negative bacterial (GNB) pathogens from the blood of inpatients at an urban public hospital to determine what proportion of these isolates carried such globally dispersed drug-resistance genes. Of 376 GNB isolates, 167 (44 %) were Escherichia coli, 50 (13 %) were Klebsiella pneumoniae, 25 (7 %) were Pseudomonas aeruginosa, 25 (7 %) were Proteus mirabilis and 20 (5 %) were Enterobacter cloacae; the remainder (24 %) comprised 26 different GNB species. Among E. coli isolates, class 1 integrons were detected in 64 (38 %). The most common integron gene cassette configuration was dfrA17-aadA5, found in 30 (25 %) of 119 drug-resistant E. coli isolates and in one isolate of Moraxella morganii. Extended-spectrum β-lactamase (ESBL) genes were found in 16 E. coli isolates (10 %). These genes with identical sequences were found in nearly 40 % of bloodstream E. coli isolates in the study hospital, as well as in a variety of bacterial species from clinical and non-clinical sources worldwide. Thus, a substantial proportion of bloodstream infections among hospitalized patients were caused by E. coli strains carrying drug-resistance genes that are dispersed globally in a wide variety of bacterial species. PMID:22493279

  6. A comparison of global, gene-specific, and relaxed clock methods in a comparative genomics framework: dating the polyploid history of soybean (Glycine max).

    PubMed

    Egan, Ashley N; Doyle, Jeff

    2010-10-01

    It is widely recognized that many genes and lineages do not adhere to a molecular clock, yet molecular clocks are commonly used to date divergences in comparative genomic studies. We test the application of a molecular clock across genes and lineages in a phylogenetic framework utilizing 12 genes linked in a 1-Mb region on chromosome 13 of soybean (Glycine max); homoeologous copies of these genes formed by polyploidy in Glycine; and orthologous copies in G. tomentella, Phaseolus vulgaris, and Medicago truncatula. We compare divergence dates estimated by two methods each in three frameworks: a global molecular clock with a single rate across genes and lineages using full and approximate likelihood methods based on synonymous substitutions, a gene-specific clock assuming rate constancy over lineages but allowing a different rate for each gene, and a relaxed molecular clock where rates may vary across genes and lineages estimated under penalized likelihood and Bayesian inference. We use the cumulative variance across genes as a means of quantifying precision. Our results suggest that divergence dating methods produce results that are correlated, but that older nodes are more variable and more difficult to estimate with precision and accuracy. We also find that models incorporating less rate heterogeneity estimate older dates of divergence than more complex models, as node age increases. A mixed model nested analysis of variance testing the effects of framework, method, and gene found that framework had a significant effect on the divergence date estimates but that most variation among dates is due to variation among genes, suggesting a need to further characterize and understand the evolutionary phenomena underlying rate variation within genomes, among genes, and across lineages.

  7. Characterization of Changes in Global Genes Expression in the Distal Colon of Loperamide-Induced Constipation SD Rats in Response to the Laxative Effects of Liriope platyphylla

    PubMed Central

    Kim, Ji Eun; Park, So Hae; Kwak, Moon Hwa; Go, Jun; Koh, Eun Kyoung; Song, Sung Hwa; Sung, Ji Eun; Lee, Hee Seob; Hong, Jin Tae; Hwang, Dae Youn

    2015-01-01

    To characterize the changes in global gene expression in the distal colon of constipated SD rats in response to the laxative effects of aqueous extracts of Liriope platyphylla (AEtLP), including isoflavone, saponin, oligosaccharide, succinic acid and hydroxyproline, the total RNA extracted from the distal colon of AEtLP-treated constipation rats was hybridized to oligonucleotide microarrays. The AEtLP treated rats showed an increase in the number of stools, mucosa thickness, flat luminal surface thickness, mucin secretion, and crypt number. Overall, compared to the controls, 581 genes were up-regulated and 216 genes were down-regulated by the constipation induced by loperamide in the constipated rats. After the AEtLP treatment, 67 genes were up-regulated and 421 genes were down-regulated. Among the transcripts up-regulated by constipation, 89 were significantly down-regulated and 22 were recovered to the normal levels by the AEtLP treatment. The major genes in the down-regulated categories included Slc9a5, klk10, Fgf15, and Alpi, whereas the major genes in the recovered categories were Cyp2b2, Ace, G6pc, and Setbp1. On the other hand, after the AEtLP treatment, ten of these genes down-regulated by constipation were up-regulated significantly and five were recovered to the normal levels. The major genes in the up-regulated categories included Serpina3n, Lcn2 and Slc5a8, whereas the major genes in the recovered categories were Tmem45a, Rerg and Rgc32. These results indicate that several gene functional groups and individual genes as constipation biomarkers respond to an AEtLP treatment in constipated model rats. PMID:26151867

  8. Effects of the Cryptochrome CryB from Rhodobacter sphaeroides on Global Gene Expression in the Dark or Blue Light or in the Presence of Singlet Oxygen

    PubMed Central

    Frühwirth, Sebastian; Teich, Kristin; Klug, Gabriele

    2012-01-01

    Several regulators are controlling the formation of the photosynthetic apparatus in the facultatively photosynthetic bacterium Rhodobacter sphaeroides. Among the proteins affecting photosynthesis gene expression is the blue light photoreceptor cryptochrome CryB. This study addresses the effect of CryB on global gene expression. The data reveal that CryB does not only influence photosynthesis gene expression but also genes for the non-photosynthetic energy metabolism like citric acid cycle and oxidative phosphorylation. In addition several genes involved in RNA processing and in transcriptional regulation are affected by a cryB deletion. Although CryB was shown to undergo a photocycle it does not only affect gene expression in response to blue light illumination but also in response to singlet oxygen stress conditions. While there is a large overlap in these responses, some CryB-dependent effects are specific for blue-light or photooxidative stress. In addition to protein-coding genes some genes for sRNAs show CryB-dependent expression. These findings give new insight into the function of bacterial cryptochromes and demonstrate for the first time a function in the oxidative stress response. PMID:22496766

  9. ERα propelled aberrant global DNA hypermethylation by activating the DNMT1 gene to enhance anticancer drug resistance in human breast cancer cells

    PubMed Central

    Lv, Jinghuan; Ding, Haijian; Zhang, Xin A.; Shao, Lipei; Yang, Nan; Cheng, He; Sun, Luan; Zhu, Dongliang; Yang, Yin; Li, Andi; Han, Xiao; Sun, Yujie

    2016-01-01

    Drug-induced aberrant DNA methylation is the first identified epigenetic marker involved in chemotherapy resistance. Understanding how the aberrant DNA methylation is acquired would impact cancer treatment in theory and practice. In this study we systematically investigated whether and how ERα propelled aberrant global DNA hypermethylation in the context of breast cancer drug resistance. Our data demonstrated that anticancer drug paclitaxel (PTX) augmented ERα binding to the DNMT1 and DNMT3b promoters to activate DNMT1 and DNMT3b genes, enhancing the PTX resistance of breast cancer cells. In support of these observations, estrogen enhanced multi-drug resistance of breast cancer cells by up-regulation of DNMT1 and DNMT3b genes. Nevertheless, the aberrant global DNA hypermethylation was dominantly induced by ERα-activated-DNMT1, since DNMT1 over-expression significantly increased global DNA methylation and DNMT1 knockdown reversed the ERα-induced global DNA methylation. Altering DNMT3b expression had no detectable effect on global DNA methylation. Consistently, the expression level of DNMT1 was positively correlated with ERα in 78 breast cancer tissue samples shown by our immunohistochemistry (IHC) analysis and negatively correlated with relapse-free survival (RFS) and distance metastasis-free survival (DMFS) of ERα-positive breast cancer patients. This study provides a new perspective for understanding the mechanism underlying drug-resistance-facilitating aberrant DNA methylation in breast cancer and other estrogen dependent tumors. PMID:26980709

  10. Improved restriction landmark cDNA scanning and its application to global analysis of genes regulated by nerve growth factor in PC12 cells.

    PubMed

    Mayumi, K; Yaoi, T; Kawai, J; Kojima, S; Watanabe, S; Suzuki, H

    1998-07-30

    Restriction landmark cDNA scanning (RLCS) is a novel method by which more than 1000 genes can be simultaneously and quantitatively displayed as two-dimensional gel spots. Here we present an adaptation that allows an individual spot to correspond to a unique gene species without redundancy in more than two gel patterns. Using this improved RLCS, we examined global changes on the gene expression of PC12 cells before and after treatment with nerve growth factor. Among a total of 3000 spots, 21 (0.70%) and 91 (3.03%) spots newly appeared and became more intense with treatment. On the other hand, 15 (0.50%) and 44 (1.47%) spots disappeared, becoming less intense with treatment. These observations suggest that approx. 6% of the detected PC12 genes are up-(3.73%) or down-(1.97%) regulated when the cells differentiate to neuronal cells. In comparison with the results obtained using the expressed-sequence-tag approach, previously reported by Lee et al. (Proc. Natl. Acad. Sci. USA 92 (1995) 8303-8307), RLCS should be useful for quantitatively examining the global change of differentially expressed genes of various expression levels. PMID:9714711

  11. Data mining

    SciTech Connect

    Lee, K.; Kargupta, H.; Stafford, B.G.; Buescher, K.L.; Ravindran, B.

    1998-12-31

    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The objective of this project was to develop and implement data mining technology suited to the analysis of large collections of unstructured data. This has taken the form of a software tool, PADMA (Parallel Data Mining Agents), which incorporates parallel data accessing, parallel scalable hierarchical clustering algorithms, and a web-based user interface for submitting Structured Query Language (SQL) queries and interactive data visualization. The authors have demonstrated the viability and scalability of PADMA by applying it to an unstructured text database of 25,000 documents running on an IBM SP2 at Argonne National Laboratory. The utility of PADMA for discovering patterns in data has also been demonstrated by applying it to laboratory test data for Hepatitis C patients and autopsy reports in collaboration with the University of New Mexico School of Medicine.

  12. The Mechanization of Mining.

    ERIC Educational Resources Information Center

    Marovelli, Robert L.; Karhnak, John M.

    1982-01-01

    Mechanization of mining is explained in terms of its effect on the mining of coal, focusing on, among others, types of mining, productivity, machinery, benefits to retired miners, fatality rate in underground coal mines, and output of U.S. mining industry. (Author/JN)

  13. Internal Transcribed Spacer rRNA Gene-Based Phylogenetic Reconstruction Using Algorithms with Local and Global Sequence Alignment for Black Yeasts and Their Relatives

    PubMed Central

    Caligiorne, R. B.; Licinio, P.; Dupont, J.; de Hoog, G. S.

    2005-01-01

    Sequences of rRNA gene internal transcribed spacer (ITS) of a standard set of black yeast-like fungal pathogens were compared using two methods: local and global alignments. The latter is based on DNA-walk divergence analysis. This method has become recently available as an algorithm (DNAWD program) which converts sequences into three-dimensional walks. The walks are compared with, or fit to, each other generating global alignments. The DNA-walk geometry defines a proper metric used to create a distance matrix appropriated for phylogenetic reconstruction. In this work, the analyses were carried out for species currently classified in Capronia, Cladophialophora, Exophiala, Fonsecaea, Phialophora, and Ramichloridium. Main groups were verified by small-subunit rRNA gene data. DNAWD applied to ITS2 alone enabled species recognition as well as phylogenetic reconstruction reflecting clades discriminated in small-subunit rRNA gene phylogeny, which was not possible with any other algorithm using local alignment for the same data set. It is concluded that DNAWD provides rapid insight into broader relationships between groups using genes that otherwise would be hardly usable for this purpose. PMID:15956403

  14. Development of the first oligonucleotide microarray for global gene expression profiling in guinea pigs: defining the transcription signature of infectious diseases

    PubMed Central

    2012-01-01

    Background The Guinea pig (Cavia porcellus) is one of the most extensively used animal models to study infectious diseases. However, despite its tremendous contribution towards understanding the establishment, progression and control of a number of diseases in general and tuberculosis in particular, the lack of fully annotated guinea pig genome sequence as well as appropriate molecular reagents has severely hampered detailed genetic and immunological analysis in this animal model. Results By employing the cross-species hybridization technique, we have developed an oligonucleotide microarray with 44,000 features assembled from different mammalian species, which to the best of our knowledge is the first attempt to employ microarray to study the global gene expression profile in guinea pigs. To validate and demonstrate the merit of this microarray, we have studied, as an example, the expression profile of guinea pig lungs during the advanced phase of M. tuberculosis infection. A significant upregulation of 1344 genes and a marked down regulation of 1856 genes in the lungs identified a disease signature of pulmonary tuberculosis infection. Conclusion We report the development of first comprehensive microarray for studying the global gene expression profile in guinea pigs and validation of its usefulness with tuberculosis as a case study. An important gap in the area of infectious diseases has been addressed and a valuable molecular tool is provided to optimally harness the potential of guinea pig model to develop better vaccines and therapies against human diseases. PMID:23031549

  15. Germ Cell Nuclear Factor (GCNF) Represses Oct4 Expression and Globally Modulates Gene Expression in Human Embryonic Stem (hES) Cells*

    PubMed Central

    Wang, Hongran; Wang, Xiaohong; Xu, Xueping; Kyba, Michael; Cooney, Austin J.

    2016-01-01

    Oct4 is considered a key transcription factor for pluripotent stem cell self-renewal. It binds to specific regions within target genes to regulate their expression and is downregulated upon induction of differentiation of pluripotent stem cells; however, the mechanisms that regulate the levels of human Oct4 expression remain poorly understood. Here we show that expression of human Oct4 is directly repressed by germ cell nuclear factor (GCNF), an orphan nuclear receptor, in hES cells. Knockdown of GCNF by siRNA resulted in maintenance of Oct4 expression during RA-induced hES cell differentiation. While overexpression of GCNF promoted repression of Oct4 expression in both undifferentiated and differentiated hES cells. The level of Oct4 repression was dependent on the level of GCNF expression in a dose-dependent manner. mRNA microarray analysis demonstrated that overexpression of GCNF globally regulates gene expression in undifferentiated and differentiated hES cells. Within the group of altered genes, GCNF down-regulated 36% of the genes, and up-regulated 64% in undifferentiated hES cells. In addition, GCNF also showed a regulatory gene pattern that is different from RA treatment during hES cell differentiation. These findings increase our understanding of the mechanisms that maintain hES cell pluripotency and regulate gene expression during the differentiation process. PMID:26769970

  16. Germ Cell Nuclear Factor (GCNF) Represses Oct4 Expression and Globally Modulates Gene Expression in Human Embryonic Stem (hES) Cells.

    PubMed

    Wang, Hongran; Wang, Xiaohong; Xu, Xueping; Kyba, Michael; Cooney, Austin J

    2016-04-15

    Oct4 is considered a key transcription factor for pluripotent stem cell self-renewal. It binds to specific regions within target genes to regulate their expression and is downregulated upon induction of differentiation of pluripotent stem cells; however, the mechanisms that regulate the levels of human Oct4 expression remain poorly understood. Here we show that expression of human Oct4 is directly repressed by germ cell nuclear factor (GCNF), an orphan nuclear receptor, in hES cells. Knockdown of GCNF by siRNA resulted in maintenance of Oct4 expression during RA-induced hES cell differentiation. While overexpression of GCNF promoted repression of Oct4 expression in both undifferentiated and differentiated hES cells. The level of Oct4 repression was dependent on the level of GCNF expression in a dose-dependent manner. mRNA microarray analysis demonstrated that overexpression of GCNF globally regulates gene expression in undifferentiated and differentiated hES cells. Within the group of altered genes, GCNF down-regulated 36% of the genes, and up-regulated 64% in undifferentiated hES cells. In addition, GCNF also showed a regulatory gene pattern that is different from RA treatment during hES cell differentiation. These findings increase our understanding of the mechanisms that maintain hES cell pluripotency and regulate gene expression during the differentiation process.

  17. Effects of DMSA-coated Fe3O4 magnetic nanoparticles on global gene expression of mouse macrophage RAW264.7 cells.

    PubMed

    Liu, Yingxun; Chen, Zhongping; Gu, Ning; Wang, Jinke

    2011-08-28

    Fe(3)O(4) magnetic nanoparticles (MNPs) coated with 2,3-dimercaptosuccinnic acid (DMSA) are considered to be a promising nanomaterial with biocompatibility. In the present study, the effects of DMSA-coated Fe(3)O(4) MNPs on the expression of all identified mouse genes, which regulate various cellular biological processes, were determined to establish whether this nanoparticle is cytotoxic to mammalian cells. Mouse macrophage RAW264.7 cells were treated with 100μg/ml of DMSA-coated Fe(3)O(4) MNPs for 4, 24 and 48h, and the global gene expression was detected via Affymetrix Mouse Genome 430 2.0 GeneChips(®) microarrays. It was found that gene expression of 711, 545 and 434 transcripts was significantly altered by 4-, 24- and 48-h treatments, respectively. Of these genes, 27 were consistently upregulated and 6 were consistently downregulated at the three treatment durations. Bioinformatic analysis of all differentially expressed genes revealed that this nanoparticle can strongly activate inflammatory and immune responses and can inhibit the biosynthesis and metabolism of RAW264.7 cells at a dose of 100μg/ml. These results demonstrated that DMSA-coated Fe(3)O(4) MNPs display cytotoxicity in this type of macrophage at high doses.

  18. Exploration and Mining Roadmap

    SciTech Connect

    none,

    2002-09-01

    This Exploration and Mining Technology Roadmap represents the third roadmap for the Mining Industry of the Future. It is based upon the results of the Exploration and Mining Roadmap Workshop held May 10 ñ 11, 2001.

  19. Surface mining

    SciTech Connect

    Not Available

    1989-06-01

    This paper reports on a GAO study of attorney and expert witness fees awarded as a result of litigation brought under the Surface Mining Control and Reclamation Act. As of March 24, 1989, a total of about $1.4 million had been awarded in attorney fees and expenses - about $1.3 subject to the provisions of the Employee Retirement Income Security Act, a comparison of its features with provisions of ERISA showed that the plan differed from ERISA provisions in areas such as eligibility, funding, and contribution limits.

  20. Mining review

    USGS Publications Warehouse

    McCartan, L.; Morse, D.E.; Plunkert, P.A.; Sibley, S.F.

    2004-01-01

    The average annual growth rate of real gross domestic product (GDP) from the third quarter of 2001 through the second quarter of 2003 in the United States was about 2.6 percent. GDP growth rates in the third and fourth quarters of 2003 were about 8 percent and 4 percent, respectively. The upward trends in many sectors of the U.S. economy in 2003, however, were shared by few of the mineral materials industries. Annual output declined in most nonfuel mining and mineral processing industries, although there was an upward turn toward yearend as prices began to increase.

  1. Impact of Global and Gene-Specific DNA Methylation in de Novo or Relapsed Acute Myeloid Leukemia Patients Treated with Decitabine.

    PubMed

    Zhang, Li-Ying; Yuan, You-Qing; Zhou, Dong-Ming; Wang, Zi-Yan; Ju, Song-Guang; Sun, Yu; Li, Jun; Fu, Jin-Xiang

    2016-01-01

    In this investigation, global DNA methylation patterns and the specific methylation status of 5 genes were studied in DNA from peripheral blood (PB) and impact on progression free survival (PFS) and overall-survival (OS) in patients with de novo or relapsed acute myeloid leukemia (AML) treated with decitabine-based regimens waas assessed. DNA was isolated from PB samples at the time of -1, 1, and 7 days of chemotherapy. Global methylation was determined by ELISA, and the CpG island DNA methylation profile of 5 genes using a DNA methylation PCR system. Our data demonstrated that patients with a high level of 5-mC had a poor prognosis after demethylation therapy and those who have low levels of 5-mC in PB achieved higher CR and better SO, but there was no significant correlation found between the 5-mC levels and other clinical features before treatment except the disease status. Higher methylation status of Sox2 and Oct4 genes was associated with differential response to demethylation therapy. A relatively low methylation percentage in one or both of these two genes was also associated with longer OS after decitabine based chemotherapy. We also suggest that global DNA and Oct-4/Sox2 methylation might impact on the pathogenesis of leukemia and play an important role in the initiation and progression. Moreover, dynamic analysis of 5-mC and Oct-4/Sox2 in peripheral blood nucleated cells of leukemia patients may provide clues to important molecular diagnostic and prognostic targets. PMID:26838251

  2. “Every Gene Is Everywhere but the Environment Selects”: Global Geolocalization of Gene Sharing in Environmental Samples through Network Analysis

    PubMed Central

    Fondi, Marco; Karkman, Antti; Tamminen, Manu V.; Bosi, Emanuele; Virta, Marko; Fani, Renato; Alm, Eric; McInerney, James O.

    2016-01-01

    The spatial distribution of microbes on our planet is famously formulated in the Baas Becking hypothesis as “everything is everywhere but the environment selects.” While this hypothesis does not strictly rule out patterns caused by geographical effects on ecology and historical founder effects, it does propose that the remarkable dispersal potential of microbes leads to distributions generally shaped by environmental factors rather than geographical distance. By constructing sequence similarity networks from uncultured environmental samples, we show that microbial gene pool distributions are not influenced nearly as much by geography as ecology, thus extending the Bass Becking hypothesis from whole organisms to microbial genes. We find that gene pools are shaped by their broad ecological niche (such as sea water, fresh water, host, and airborne). We find that freshwater habitats act as a gene exchange bridge between otherwise disconnected habitats. Finally, certain antibiotic resistance genes deviate from the general trend of habitat specificity by exhibiting a high degree of cross-habitat mobility. The strong cross-habitat mobility of antibiotic resistance genes is a cause for concern and provides a paradigmatic example of the rate by which genes colonize new habitats when new selective forces emerge. PMID:27190206

  3. Global tr