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At least 1,657 records · Page 92Linked to original sources
PubMed2006

Virus-like particles of the Ty3 retrotransposon assemble in association with P-body components.

Retroviruses and retrotransposons assemble intracellular immature core particles around a RNA genome, and nascent particles collect in association with membranes or as intracellular clusters. How and where genomic RNA are identified for retrovirus and retrotransposon assembly, and how translation and assembly processes are coordinated is poorly understood. To understand this process, the subcellular localization of Ty3 RNA and capsid proteins and virus-like particles was investigated. We demonstrate that mRNAs, proteins, and virus-like particles of the yeast Ty3 retrotransposon accumulate in association with cytoplasmic P-bodies, which are sites of mRNA translation repression, storage, and degradation. Deletions of genes encoding P-body proteins decreased Ty3 transposition and caused changes in the pattern of Ty3 foci, underscoring the biological significance of the association of Ty3 virus-like protein components and P-bodies. These results suggest the hypothesis that P-bodies may serve to segregate translation and assembly functions of the Ty3 genomic RNA to promote assembly of virus-like particles. Because Ty3 has features of a simple retrovirus and P-body functions are conserved between yeast and metazoan organisms, these findings may provide insights into host factors that facilitate retrovirus assembly.

Inclusion Bodies↗
PubMed2004

Expression genomics and cancer biology.

Expression genomics is a term that is used to describe the investigation of transcription in a whole-genome manner and includes the investigation of gene regulation. Characteristic of this approach is its comprehensiveness and the highly multiplexed nature of its analysis. Thus, the range of technologies used include microarrays, tag library approaches, such as serial analysis of gene expression (SAGE), full-length cDNA cloning and sequencing, and chromatin immunoprecipitation coupled with cloning/sequencing or applied to genomic chips. These technologies are all complementary since they have different capabilities and attack different components of the transcriptome: transcriptional regulation, promoter usage, differential splicing, and gene expression. Unlike genome sequencing, the combinatorial complexity of the transcriptome is immense, making its complete characterization impossible. Instead, the strategy has shifted to the analysis of the whole transcriptome in a context-driven, cell biological framework where the fundamental truths emerge through multiple comparisons and pharmacological challenges. The density of non-redundant data generated with any experiment allows for the assessment of higher order relationships. This comprehensive data, in turn, permits information convergence across different experiments, organisms, and data sets. Surprising concordance in the underlying conclusions is observed with data of such complexity. Since microarrays have been the most widely used technology in expression genomics for the study of cancer biology, this paper will focus on studies using expression arrays, but will also touch on other transcriptome-directed technologies. The experience with these approaches is sufficiently mature to arrive at some generalizable observations. First, although expression genomics is a useful approach for the discovery of individual candidate genes, its greatest power is in defining class distinctions using the collective behavior of gene clusters. Therefore, expression genomic output can effectively uncover hierarchies of molecular importance. Second, in the hierarchy of factors that determine the expression footprint within a cell, cell lineage is the most important, followed by the activity of specific biochemical pathways and further followed by the effect of individual genes. Lastly, expression profiling is an effective clinical tool that can discern prognostic and therapeutic classes. The importance of these gene lists is that not only do they describe potential therapeutic targets, but they are effective monitors of therapeutic efficacy.

Animals↗
PubMed2000

American Society of Microbiology - 100th General Meeting.

Symposium sessions on genomics, surveillance, and pharmaceutical intervention opportunities were highlights of this annual ASM meeting. Two-component signal transduction was highlighted by both academic and industrial representatives, as was prokaryotic genomics. Recurring themes throughout the meeting were the contribution of efflux mechanisms to worldwide resistance, target modifications responsible for fluoroquinolone resistance, and the role of structural biology in the discovery and exploitation of bacterial targets.

Journal Article↗
PubMed2005

Post-genomics of microsporidia, with emphasis on a model of minimal eukaryotic proteome: a review.

The genome sequence of the microsporidian parasite Encephalitozoon cuniculi Levaditi, Nicolau et Schoen, 1923 contains about 2,000 genes that are representative of a non-redundant potential proteome composed of 1,909 protein chains. The purpose of this review is to relate some advances in the characterisation of this proteome through bioinformatics and experimental approaches. The reduced diversity of the set of E. cuniculi proteins is perceptible in all the compilations of predicted domains, orthologs, families and superfamilies, available in several public databases. The phyletic patterns of orthologs for seven eukaryotic organisms support an extensive gene loss in the fungal clade, with additional deletions in E. cuniculi. Most microsporidial orthologs are the smallest ones among eukaryotes, justifying an interest in the use of these compacted proteins to better discriminate between essential and non-essential regions. The three components of the E. cuniculi mRNA capping apparatus have been especially well characterized and the three-dimensional structure of the cap methyltransferase has been elucidated following the crystallisation of the microsporidial enzyme Ecm1. So far, our mass spectrometry-based analyses of the E. cuniculi spore proteome has led to the identification of about 170 proteins, one-quarter of these having no clearly predicted function. Immunocytochemical studies are in progress to determine the subcellular localisation of microsporidia-specific proteins. Post-translational modifications such as phosphorylation and glycosylation are expected to be soon explored.

Animals↗
PubMed2007

Non-genomic transgenerational inheritance of disease risk.

That there is a heritable or familial component of susceptibility to chronic non-communicable diseases such as type 2 diabetes, obesity and cardiovascular disease is well established, but there is increasing evidence that some elements of such heritability are transmitted non-genomically and that the processes whereby environmental influences act during early development to shape disease risk in later life can have effects beyond a single generation. Such heritability may operate through epigenetic mechanisms involving regulation of either imprinted or non-imprinted genes but also through broader mechanisms related to parental physiology or behaviour. We review evidence and potential mechanisms for non-genomic transgenerational inheritance of 'lifestyle' disease and propose that the 'developmental origins of disease' phenomenon is a maladaptive consequence of an ancestral mechanism of developmental plasticity that may have had adaptive value in the evolution of generalist species such as Homo sapiens.

Animals↗
PubMed2003

Structure and evolution of the Cinful retrotransposon family of maize.

A maize cDNA clone was isolated by virtue of its intense hybridization to total maize genomic DNA, indicating homology to highly repetitive sequences. Genomic homologues were identified and subcloned from an adh1-bearing maize yeast artificial chromosome (YAC). Sequencing revealed that the expressed sequence was part of a Ty3-gypsy-type retrotransposon. We discovered and sequenced two complete retrotransposons of this family, and named them Cinful elements because they are members of a family of maize retrotransposons including Zeon-1 and the first plant transposable element sequenced, the solo long terminal repeat (LTR) called Cin1. All are defective, as Cinful-1 and Cinful-2 elements lack gag and Zeon-1 lacks pol homology. Despite the apparent lack of an intact "autonomous" element, the Cinful family has expanded to a copy number of about 18 000, representing just under 9% of the maize genome. Both point mutations and major rearrangements, including possible gene acquisition, differentiate members of the Cinful family. Cinful family members were found to have an unusual feature that we also observed in two other Ty3-class retrotransposons of teosinte and tobacco: related tandem repeats that separate their internal domains with a gag- or pol-containing homology from a 3' segment of unknown function. The conserved and variable features identified provide insights into the origin, mutational history, and functional components of this major constituent of the maize genome.

Amino Acid Sequence↗
PubMed2006

SeqHepB: a sequence analysis program and relational database system for chronic hepatitis B.

SeqHepB is a combination of a HBV genome sequence analysis program and a relational database that houses data collected from multiple data sources. Registered users can access the sequence analysis component of SeqHepB online for rapid and detailed interrogation of HBV genomic sequences. Its main function is to determine the HBV genotype, identify key mutations associated with antiviral resistance, and identify clinically important HBV mutants. All information generated is uploaded into a database and integrated with patient medical records, pathology laboratory tests, and supplemental virology results such as in vitro drug cross-resistance values. Combined with structured query language (SQL) queries developed in the database, it is possible to extract and correlate clinical, virological, and in vitro phenotypic data rapidly and efficiently. An important component of SeqHepB is its ability to integrate mutations detected within the reverse transcriptase (RT) and locate them onto a three-dimensional (3D) model of the HBV RT that can be viewed at any angle with known antiviral drug molecules in the catalytic pocket of the enzyme. SeqHepB will enable virologists and physicians to individualise patient management, cope with the explosion of antiviral associated HBV mutations, and to conduct cross-sectional retrospective or prospective studies on HBV-infected individuals during therapy.

DNA Mutational Analysis↗
PubMed2006

Insect immunity: the post-genomic era.

Insects have a complex and effective immune system, many components of which are conserved in mammals. But only in the last decade have the molecular mechanisms that regulate the insect immune response--and their relevance to general biology and human immunology--become fully appreciated. A meeting supported by the Centre National de la Récherche Scientifique (France) was held to bring together the whole spectrum of researchers working on insect immunity. The meeting addressed diverse aspects of insect immunity and brought together geneticists working on Drosophila melanogaster with those working on other insects.

Animals↗
PubMed1979

Base composition heterogeneity of Euglena gracilis chloroplast DNA.

Euglena gracilis chloroplast DNA has an average buoyant density of 1.685 gm/cm3, corresponding to 25 mol% G . C base pairs. To test for base compositional heterogeneity within this 130 kilobase pairs (kbp) genome, previously mapped restriction endonuclease fragments were isolated, and characterized by equilibrium buoyant density centrifugation. The chloroplast DNA can be characterized as containing two major buoyant density components. A segment of 17 kbp, representing 13% of the genome and containing the rRNA genes is 43--44 mol% G . C. The remaining 113 kbp, accounting for 87% of the genome, has an average 20--21 mol% G . C content.

Animals↗
PubMed2003

Obesity and diabetes gene discovery approaches.

New treatments are currently required for the common metabolic diseases obesity and type 2 diabetes. The identification of physiological and biochemical factors that underlie the metabolic disturbances observed in obesity and type 2 diabetes is a key step in developing better therapeutic outcomes. The discovery of new genes and pathways involved in the pathogenesis of these diseases is critical to this process, however identification of genes that contribute to the risk of developing these diseases represents a significant challenge as obesity and type 2 diabetes are complex diseases with many genetic and environmental causes. A number of diverse approaches have been used to discover and validate potential new targets for obesity and diabetes. To date, DNA-based approaches using candidate gene and genome-wide linkage analysis have had limited success in identifying genomic regions or genes involved in the development of these diseases. Recent advances in the ability to evaluate linkage analysis data from large family pedigrees using variance components based linkage analysis show great promise in robustly identifying genomic regions associated with the development of obesity and diabetes. RNA-based technologies such as cDNA microarrays have identified many genes differentially expressed in tissues of healthy and diseased subjects. Using a combined approach, we are endeavouring to focus attention on differentially expressed genes located in chromosomal regions previously linked with obesity and/or diabetes. Using this strategy, we have identified Beacon as a potential new target for obesity and diabetes.

Amino Acid Sequence↗
PubMed1999

Virus reconstitution and the proof of the existence of genomic RNA.

This paper is a historical overview of the work done on the tobacco mosaic virus. The primary finding was that a virus is capable of reassembling itself from its component protein and RNA, and that only the RNA carries the genomic capability of the virus. This was followed by detailed studies of the chemical and biological properties of viral RNA.

Plants, Toxic↗
PubMed2005

Genome-wide linkage analysis of mandibular prognathism in Korean and Japanese patients.

The existence of familial aggregation of mandibular prognathism (MP) suggests that genetic components play an important role in its etiology. In this study, a genome-wide linkage analysis to identify loci susceptible to MP was conducted with 90 affected sibling-pairs in 42 families, comprised of 40 Korean sibling-pairs and 50 Japanese sibling-pairs. Two non-parametric linkage analyses, GENEHUNTER-PLUS and SIBPAL, were applied and detected nominal statistical significance of linkage to MP at chromosomes 1p36, 6q25, and 19p13.2. The best evidence of linkage was detected near D1S234 (maximum Z(lr) = 2.51, P = 0.0012). In addition, evidence of linkage was observed near D6S305 (maximum Z(lr) = 2.23, P = 0.025) and D19S884 (maximum Z(lr) = 1.93, P = 0.0089). Identification of the susceptible genes in the linkage regions will pave the way for insights into the molecular pathways that cause MP, especially overgrowth of the mandible, and may lead to the development of novel therapeutic tools.

Adolescent↗
PubMed1999

A view from the genome: spatial control of transcription in sea urchin development.

The process of embryogenesis depends on differential regulation of genes in the spatial components defined by the embryonic cells (blastomeres). Developmental regulation is mediated by complex, hardwired genomic control systems consisting of clusters of multiple target sites at which specific interactions with regionally presented transcription factors occur. In the age of genomics and gene-transfer technology, the sea urchin embryo provides unique opportunities for experimental analysis of these processes. Research on gene regulation in sea urchin embryos in the past year has seen remarkable progress in two large areas: in understanding functional cis-regulatory architecture; and in understanding the mechanism by which the axial coordinates of the egg are transduced into a molecular system for differential gene activation.

Animals↗
PubMed2006

Isolation and characterization of SSR sequences from the genome and TAC clones of common wheat using the PCR technique.

We have developed the 2-step PCR method, a kind of suppression PCR procedure, to isolate simple sequence repeats (SSRs) from common wheat (Triticum aestivum L.) in a more convenient manner. This system requires neither genomic library screening nor the SSR-enrichment procedure. As a result, we designed 131 primer pairs based on isolated SSRs from not only genomic DNA, but also transformation-competent artificial chromosome (TAC) clones. It has been demonstrated that 34 of the 131 SSR markers developed were polymorphic among 8 wheat lines. Four of 34 polymorphic SSR markers were derived from TAC clones, indicating that this method could be applied to the targeted development of unique SSR markers in large genomic DNA libraries such as those composed of bacterial artificial chromosomes (BACs). A considerable number of isolated SSR clones had similarities with part of several long terminal repeats of retrotransposons (LTR-RTs) identified in various Triticeae genome sequences. Most of those SSRs showed smear amplification profiles, suggesting that a considerable number of dysfunctional SSRs originating from repetitive DNA components, especially LTR-RTs, might exist in the common wheat genome.

Base Sequence↗
PubMed1996

[Oncogenes and the malignancy process].

An important group of genes for the development of neoplastic diseases are, in addition to tumour suppressor genes, protooncogenes. The latter are highly preserved genes present in a similar sequence in the cell genomes of different species (yeasts - man). They encode components of biochemical signalling pathways by which external mitotic signals stimulate cell proliferation and products which inhibit cell differentiation. The result of activation of protooncogenes into oncogenes (mutations, chromosomal rearrangements, amplifications, viral insertions, insertion mutagenesis) is in particular hyperstimulation of cells resulting in uncontrolled proliferation. Mutations are of the dominant type, elimination of one allele leads to the transformation of a protooncogene into an oncogene. Oncogenes are classified with regard to the transmission level of the mitogenic signal on which they act. Originally they were detected in the genome of oncogenic viruses. However, they do not form their constant and specific constituent, the virus acts as a vector which transmits cellular protooncogenes (or oncogenes) during the reproductive cycle from one cell to another. The activity of various types of oncogenes is the necessary prerequisite for the genesis and development of various neoplastic diseases. Detection of oncogene alterations provides in some instances important diagnostic, prognostic and therapeutic findings.

Gene Expression Regulation, Neoplastic↗
PubMed2026

Two-sample Mendelian randomization study of gut microbiota and inflammatory proteins: Predictive, preventive, and personalized treatment for migraine.

The human gut microbiota is increasingly recognized as a significant factor in the pathogenesis of migraine, potentially via inflammatory pathways. Identifying specific human gut microbiota components associated with migraines, along with the investigation of particular inflammatory proteins, is essential for advancing primary prediction, targeted prevention, and personalized treatment strategies for migraines. We conducted a two-sample Mendelian randomization study using publicly available summary statistics from genome-wide association studies. Data for 473 human gut microbiota taxa were obtained from the Finnish national health survey conducted by the National Institute for Health and Welfare study (FINRISK, n = 5959 European participants). Genome-wide association study data (https://www.ebi.ac.uk/gwas/) for 91 circulating inflammatory proteins were obtained from 14,824 participants across 11 cohorts using the Olink Target 96 Inflammation panel. Migraine outcome data were obtained from the FinnGen R12 release, with cases defined using ICD-10 code G43. All genome-wide association study analyses were adjusted for sex, age, genotyping batch, and 10 genetic principal components to control population stratification (genomic inflation factors: 1.00–1.05). Inverse variance-weighted Mendelian randomization was the primary analysis method, with Mendelian randomization-Egger, weighted median, and mode-based methods as sensitivity analyses. Two-step Mendelian randomization mediation analysis quantified the proportion of the effects of human gut microbiota on migraine that are mediated through inflammatory proteins. Thirty-seven bacterial genera were found to be associated with migraine using the inverse variance-weighted method. Of these, 18 genera exhibited a negative association, while 19 genera demonstrated a positive association with migraine risk. Additionally, eight inflammatory proteins were found to increase the risk of migraine. Among human gut microbiota, four were observed to reduce inflammatory protein levels, whereas another four were associated with increased inflammatory protein levels. Additionally, five gut microbiota were identified to influence migraine through inflammatory proteins in both Mendelian randomization analyses. Specifically, Actinobacteria, Brachyspiraceae, CAG-269 sp001915995, and Paraglaciecola were found to affect migraine outcomes via inflammatory proteins, with mediation proportions of 12%, 19%, 15.5%, and 6.7%, respectively. Lawsonibacter sp002161175 was identified to influence migraine risk through Oncostatin-M and SLAM, with mediation proportions of 15.6% and 11.3%, respectively. Our study elucidated the role of specific human gut microbiota alterations in the pathogenesis of migraine and highlighted the mediating effects of inflammatory proteins. Targeting these particular human gut microbiota alterations offers a promising strategy for predictive, preventive, and personalized medicine in migraine management, resulting in substantial clinical advancements.

causality↗
PubMed2003

The mitochondrial genome of the thermal dimorphic fungus Penicillium marneffei is more closely related to those of molds than yeasts.

We report the complete sequence of the mitochondrial genome of Penicillium marneffei, the first complete mitochondrial DNA sequence of a thermal dimorphic fungus. This 35 kb mitochondrial genome contains the genes encoding ATP synthase subunits 6, 8, and 9 (atp6, atp8, and atp9), cytochrome oxidase subunits I, II, and III (cox1, cox2, and cox3), apocytochrome b (cob), reduced nicotinamide adenine dinucleotide ubiquinone oxireductase subunits (nad1, nad2, nad3, nad4, nad4L, nad5, and nad6), ribosomal protein of the small ribosomal subunit (rps), 28 tRNAs, and small and large ribosomal RNAs. Analysis of gene contents, gene orders, and gene sequences revealed that the mitochondrial genome of P. marneffei is more closely related to those of molds than yeasts.

Base Sequence↗
PubMed2006

Exopolysaccharide-associated protein sorting in environmental organisms: the PEP-CTERM/EpsH system. Application of a novel phylogenetic profiling heuristic.

BACKGROUND: Protein translocation to the proper cellular destination may be guided by various classes of sorting signals recognizable in the primary sequence. Detection in some genomes, but not others, may reveal sorting system components by comparison of the phylogenetic profile of the class of sorting signal to that of various protein families. RESULTS: We describe a short C-terminal homology domain, sporadically distributed in bacteria, with several key characteristics of protein sorting signals. The domain includes a near-invariant motif Pro-Glu-Pro (PEP). This possible recognition or processing site is followed by a predicted transmembrane helix and a cluster rich in basic amino acids. We designate this domain PEP-CTERM. It tends to occur multiple times in a genome if it occurs at all, with a median count of eight instances; Verrucomicrobium spinosum has sixty-five. PEP-CTERM-containing proteins generally contain an N-terminal signal peptide and exhibit high diversity and little homology to known proteins. All bacteria with PEP-CTERM have both an outer membrane and exopolysaccharide (EPS) production genes. By a simple heuristic for screening phylogenetic profiles in the absence of pre-formed protein families, we discovered that a homolog of the membrane protein EpsH (exopolysaccharide locus protein H) occurs in a species when PEP-CTERM domains are found. The EpsH family contains invariant residues consistent with a transpeptidase function. Most PEP-CTERM proteins are encoded by single-gene operons preceded by large intergenic regions. In the Proteobacteria, most of these upstream regions share a DNA sequence, a probable cis-regulatory site that contains a sigma-54 binding motif. The phylogenetic profile for this DNA sequence exactly matches that of three proteins: a sigma-54-interacting response regulator (PrsR), a transmembrane histidine kinase (PrsK), and a TPR protein (PrsT). CONCLUSION: These findings are consistent with the hypothesis that PEP-CTERM and EpsH form a protein export sorting system, analogous to the LPXTG/sortase system of Gram-positive bacteria, and correlated to EPS expression. It occurs preferentially in bacteria from sediments, soils, and biofilms. The novel method that led to these findings, partial phylogenetic profiling, requires neither global sequence clustering nor arbitrary similarity cutoffs and appears to be a rapid, effective alternative to other profiling methods.

Amino Acid Motifs↗