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At least 1,297 records · Page 72Linked to original sources
PubMed2006

Marek's disease virus: from miasma to model.

Marek's disease virus (MDV) is an oncogenic herpesvirus that causes various clinical syndromes in its natural host, the chicken. MDV has long been of interest as a model organism, particularly with respect to the pathogenesis and immune control of virus-induced lymphoma in an easily accessible small-animal system. Recent advances in MDV genetics and the determination of the chicken genome sequence, aided by functional genomics, have begun to dramatically increase our understanding not only of lytic MDV replication, but also of the factors and mechanisms leading to latency and tumour formation. This new information is helping to elucidate cellular signalling pathways that have undergone convergent evolution and are perturbed by different viruses, and emphasizes the value of MDV as a comparative biomedical model. Furthermore, the door is now open for rational and efficient engineering of new vaccines against one of the most important and widespread infectious diseases in chickens.

Animals↗
PubMed2004

Identification of p53 regulators by genome-wide functional analysis.

The p53 tumor-suppressor protein is a critical mediator of cellular growth arrest and the induction of apoptosis. To identify proteins involved in the modulation of p53 transcriptional activity, a gain-of-function cellular screen was carried out with an arrayed matrix of approximately 20,000 cDNAs. Nine genes previously unknown to be involved in regulating p53 activity were identified. Overexpression of seven of these genes (Hey1, Hes1, TFAP4, Osr1, NR2F2, SFRS10, and FLJ11339) resulted in up-regulation of p53 activity; overexpression of two genes (M17S2 and cathepsin B) resulted in down-regulation of p53 activity in mammalian cells. HES1, HEY1, and TFAP4, which are members of the basic helix-loop-helix transcription family, and OSR1 were shown to activate p53 through repression of HDM2 transcription. Ectopic expression of these basic helix-loop-helix transcription factors in both zebrafish and avian developmental systems activated p53 and induced apoptosis in vivo, resulting in a phenotype similar to that of p53 overexpression. Furthermore, ras- and myc-mediated transformation of mouse embryonic fibroblasts was abrogated by expression of HEY1 in a p53-dependent manner. These results suggest that these transcription factors are members of an evolutionarily conserved network that governs p53 function.

Animals↗
PubMed2001

Infectious diseases: considerations for the 21st century.

The discipline of infectious diseases will assume added prominence in the 21st century in both developed and developing nations. To an unprecedented extent, issues related to infectious diseases in the context of global health are on the agendas of world leaders, health policymakers, and philanthropies. This attention has focused both on scientific challenges such as vaccine development and on the deleterious effects of infectious diseases on economic development and political stability. Interest in global health has led to increasing levels of financial support, which, combined with recent technological advances, provide extraordinary opportunities for infectious disease research in the 21st century. The sequencing of human and microbial genomes and advances in functional genomics will underpin significant progress in many areas, including understanding human predisposition and susceptibility to disease, microbial pathogenesis, and the development new diagnostics, vaccines, and therapies. Increasingly, infectious disease research will be linked to the development of the medical infrastructure and training needed in developing countries to translate scientific advances into operational reality.

Bioterrorism↗
PubMed2002

Mapping baroreceptor function to genome: a mathematical modeling approach.

To gain information about the genetic basis of a complex disease such as hypertension, blood pressure averages are often obtained and used as phenotypes in genetic mapping studies. In contrast, direct measurements of physiological regulatory mechanisms are not often obtained, due in large part to the time and expense required. As a result, little information about the genetic basis of physiological controlling mechanisms is available. Such information is important for disease diagnosis and treatment. In this article, we use a mathematical model of blood pressure to derive phenotypes related to the baroreceptor reflex, a short-term controller of blood pressure. The phenotypes are then used in a quantitative trait loci (QTL) mapping study to identify a potential genetic basis of this controller.

Animals↗
PubMed2006

QTL MatchMaker: a multi-species quantitative trait loci (QTL) database and query system for annotation of genes and QTL.

Identifying genes that underlie quantitative trait loci (QTL) is a challenging task. Here, we present a new QTL software system, named QTL MatchMaker. The system is designed to integrate and mine QTL information across human, mouse and rat genomes and to annotate functional genomic data. It combines and organizes information from relevant public databases and publications and integrates QTL, physical, genetic and cytogenetic maps across human, mouse and rat. To make this application available to the research community we have developed a website for high-throughput mapping of expressed sequences to QTL and for selection of candidate genes in the physiological genomics context of complex traits. QTL MatchMaker is accessible at http://pmrc.med.mssm.edu:9090/QTL/jsp/qtlhome.jsp.

Animals↗
PubMed1996

A murine RNA polymerase I promoter inserted into the herpes simplex virus type 1 genome is functional during lytic, but not latent, infection.

The development of herpes simplex virus as a vector for neuronal gene delivery is dependent upon the identification and characterization of promoter elements capable of driving long-term expression during latency. The majority of RNA polymerase II (pol II) promoters studied are active during acute infection but silenced during latency. In order to investigate the potential of a murine RNA polymerase I (pol I) promoter to drive reporter gene expression during lytic and latent infection, we describe the construction and characterization of two recombinant viruses; SC16 LAT neo and SC16 US5 neo. These viruses contain a pol I-encephalomyocarditis virus internal ribosome entry site (EMCV IRES)-neomycin phosphotransferase gene (neoR) cassette inserted into the non-essential major latency associated transcript (LAT) and US5 regions respectively. Pol I promoter activity could be detected in the rodent BHK cell line, but not the primate derived Vero cell line-- consistent with the known species specificity of such promoters. This activity was specific to a virus containing an active pol I promoter. However, in situ hybridization analyses of latently infected cervical dorsal root ganglia failed to detect pol I mediated transcription of the reporter gene indicating that the murine pol I promoter is silenced following the establishment of latency. Insertion of the pol I-EMCV IRES-neoR cassette into the major LAT locus resulted in the production of a hybrid LAT transcript during latency which was translocated to the cytoplasm of latently infected neurones.

Animals↗
PubMed2006

Genomic and functional analysis of the IncP-9 naphthalene-catabolic plasmid NAH7 and its transposon Tn4655 suggests catabolic gene spread by a tyrosine recombinase.

The naphthalene-catabolic (nah) genes on the incompatibility group P-9 (IncP-9) self-transmissible plasmid NAH7 from Pseudomonas putida G7 are some of the most extensively characterized genetic determinants for bacterial aerobic catabolism of aromatic hydrocarbons. In contrast to the detailed studies of its catabolic cascade and enzymatic functions, the biological characteristics of plasmid NAH7 have remained unclear. Our sequence determination in this study together with the previously deposited sequences revealed the entire structure of NAH7 (82,232 bp). Comparison of NAH7 with two other completely sequenced IncP-9 catabolic plasmids, pDTG1 and pWW0, revealed that the three plasmids share very high nucleotide similarities in a 39-kb region encoding the basic plasmid functions (the IncP-9 backbone). The backbone of NAH7 is phylogenetically more related to that of pDTG1 than that of pWW0. These three plasmids carry their catabolic gene clusters at different positions on the IncP-9 backbone. All of the NAH7-specified nah genes are located on a class II transposon, Tn4655. Our analysis of the Tn4655-encoded site-specific recombination system revealed that (i) a novel tyrosine recombinase, TnpI, catalyzed both the intra- and intermolecular recombination between two copies of the attI site, (ii) the functional attI site was located within a 119-bp segment, and (iii) the site-specific strand exchange occurred within a 30-bp segment in the 41-bp CORE site. Our results and the sequence data of other naphthalene-catabolic plasmids, pDTG1 and pND6-1, suggest a potential role of the TnpI-attI recombination system in the establishment of these catabolic plasmids.

Bacterial Proteins↗
PubMed2001

Combined, functional genomic-biochemical approach to intermediary metabolism: interaction of acivicin, a glutamine amidotransferase inhibitor, with Escherichia coli K-12.

Acivicin, a modified amino acid natural product, is a glutamine analog. Thus, it might interfere with metabolism by hindering glutamine transport, formation, or usage in processes such as transamidation and translation. This molecule prevented the growth of Escherichia coli in minimal medium unless the medium was supplemented with a purine or histidine, suggesting that the HisHF enzyme, a glutamine amidotransferase, was the target of acivicin action. This enzyme, purified from E. coli, was inhibited by low concentrations of acivicin. Acivicin inhibition was overcome by the presence of three distinct genetic regions when harbored on multicopy plasmids. Comprehensive transcript profiling using DNA microarrays indicated that histidine biosynthesis was the predominant process blocked by acivicin. The response to acivicin, however, was quite complex, suggesting that acivicin inhibition resonated through more than a single cellular process.

Aminohydrolases↗
PubMed2000

Leader proteinase of the beet yellows closterovirus: mutation analysis of the function in genome amplification.

The beet yellows closterovirus leader proteinase (L-Pro) possesses a C-terminal proteinase domain and a nonproteolytic N-terminal domain. It was found that although L-Pro is not essential for basal-level replication, deletion of its N-terminal domain resulted in a 1, 000-fold reduction in RNA accumulation. Mutagenic analysis of the N-terminal domain revealed its structural flexibility except for the 54-codon-long, 5'-terminal element in the corresponding open reading frame that is critical for efficient RNA amplification at both RNA and protein levels.

Closterovirus↗
PubMed2005

Marine genomics: a clearing-house for genomic and transcriptomic data of marine organisms.

BACKGROUND: The Marine Genomics project is a functional genomics initiative developed to provide a pipeline for the curation of Expressed Sequence Tags (ESTs) and gene expression microarray data for marine organisms. It provides a unique clearing-house for marine specific EST and microarray data and is currently available at http://www.marinegenomics.org. DESCRIPTION: The Marine Genomics pipeline automates the processing, maintenance, storage and analysis of EST and microarray data for an increasing number of marine species. It currently contains 19 species databases (over 46,000 EST sequences) that are maintained by registered users from local and remote locations in Europe and South America in addition to the USA. A collection of analysis tools are implemented. These include a pipeline upload tool for EST FASTA file, sequence trace file and microarray data, an annotative text search, automated sequence trimming, sequence quality control (QA/QC) editing, sequence BLAST capabilities and a tool for interactive submission to GenBank. Another feature of this resource is the integration with a scientific computing analysis environment implemented by MATLAB. CONCLUSION: The conglomeration of multiple marine organisms with integrated analysis tools enables users to focus on the comprehensive descriptions of transcriptomic responses to typical marine stresses. This cross species data comparison and integration enables users to contain their research within a marine-oriented data management and analysis environment.

Animals↗
PubMed1997

The hardwiring of development: organization and function of genomic regulatory systems.

The gene regulatory apparatus that directs development is encoded in the DNA, in the form of organized arrays of transcription factor target sites. Genes are regulated by interactions with multiple transcription factors and the target sites for the transcription factors required for the control of each gene constitute its cis-regulatory system. These systems are remarkably complex. Their hardwired internal organization enables them to behave as genomic information processing systems. Developmental gene regulatory networks consist of the cis-regulatory systems of all the relevant genes and the regulatory linkages amongst them. Though there is yet little explicit information, some general properties of genomic regulatory networks have become apparent. The key to understanding how genomic regulatory networks are organized, and how they work, lies in experimental analysis of cis-regulatory systems at all levels of the regulatory network.

Animals↗
PubMed2000

Current millennium biotechniques for biomedical research on parasites and host-parasite interactions.

The development of biotechnology in the last three decades has generated the feeling that the newest scientific achievements will deliver high standard quality of life through abundance of food and means for successfully combating diseases. Where the new biotechnologies give access to genetic information, there is a common belief that physiological and pathological processes result from subtle modifications of gene expression. Trustfully, modern genetics has produced genetic maps, physical maps and complete nucleotide sequences from 141 viruses, 51 organelles, two eubacteria, one archeon and one eukaryote (Saccharomices cerevisiae). In addition, during the Centennial Commemoration of the Oswaldo Cruz Institute the nearly complete human genome map was proudly announced, whereas the latest Brazilian key stone contribution to science was the publication of the Shillela fastidiosa genomic sequence highlythed on a Nature cover issue. There exists a belief among the populace that further scientific accomplishments will rapidly lead to new drugs and methodological approaches to cure genetic diseases and other incurable ailments. Yet, much evidence has been accumulated, showing that a large information gap exists between the knowledge of genome sequence and our knowledge of genome function. Now that many genome maps are available, people wish to know what are we going to do with them. Certainly, all these scientific accomplishments will shed light on many more secrets of life. Nevertheless, parsimony in the weekly announcements of promising scientific achievements is necessary. We also need many more creative experimental biologists to discover new, as yet un-envisaged biotechnological approaches, and the basic resource needed for carrying out mile stone research necessary for leading us to that "promised land" often proclaimed by the mass media.

Animals↗
PubMed2005

An effective approach to assay plant response to environmental factors--DNA microarray.

With huge plant DNA data released by genome sequence project, the high-throughput DNA microarray technology has been proven an effective way to bridge the gap between plant genome sequence information and functional genomics. The technology has been used to investigate the gene expression patterns and to elucidate the role of genes. In this review, we briefly outline the features of DNA microarray and highlight its recent applications in plant biology, especially in the identification of stress-response elements and in the clarification of plant signal network.

Disasters↗
PubMed2002

[Advances in studies of genome-specific repetitive DNA sequences in wheat and related species].

In this paper we review recent advances in studies of several aspects of genome specific repetitive DNA sequences in wheat and related species. The available results demonstrate that genome specific repetitive DNA sequences are important components of genome specificity in wheat and related species. Research on genome specific repetitive DNA sequences is essential to the elucidation of genome function. The application of genome specific repetitive DNA sequences will aid molecular cytogenetic studies in wheat and related species and contributes to genetic improvement of common wheat.

English Abstract↗