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At least 1,081 records · Page 60Linked to original sources
PubMed2005

Genomic and functional characterization of stellate cells isolated from human cirrhotic livers.

BACKGROUND/AIMS: Hepatic stellate cells (HSCs) are believed to participate in liver fibrogenesis and portal hypertension. Knowledge on human HSCs is based on studies using HSCs isolated from normal livers. We investigated the phenotypic, genomic and functional characteristics of HSCs from human cirrhotic livers. METHODS: HSC were obtained from normal and cirrhotic human livers. Cells were characterized by immunocytochemistry and gene microarray analysis. Cell proliferation, Ca(2+) changes and cell contraction were assessed by 3H-thymidine incorporation and by using an epifluorescence microscope. RESULTS: HSCs freshly isolated from human cirrhotic livers showed phenotypical features of myofibroblasts. These features were absent in HSCs freshly isolated from normal human livers and become prominent after prolonged culture. HSCs from cirrhotic human livers markedly express genes involved in fibrogensis, inflammation and apoptosis. HSCs from normal livers after prolonged culture preferntially expressed genes related to fibrogenesis and contractility. Agonists induced proliferation, Ca(2+) increase and cell contraction in HSCs isolated from human cirrhotic livers. Response to agonists was more marked in culture-activated HSCs and was not observed in HSCs freshly isolated from normal livers. CONCLUSIONS: HSCs from human cirrhotic livers show fibrogenic and contractile features. However, the current model of HSCs activated in culture does not exactly reproduce the activated phenotype found in cirrhotic human livers.

Calcium↗
PubMed2004

Arabidopsis to rice. Applying knowledge from a weed to enhance our understanding of a crop species.

Although Arabidopsis is well established as the premiere model species in plant biology, rice (Oryza sativa) is moving up fast as the second-best model organism. In addition to the availability of large sets of genetic, molecular, and genomic resources, two features make rice attractive as a model species: it represents the taxonomically distinct monocots and is a crop species. Plant structural genomics was pioneered on a genome-scale in Arabidopsis and the lessons learned from these efforts were not lost on rice. Indeed, the sequence and annotation of the rice genome has been greatly accelerated by method improvements made in Arabidopsis. For example, the value of full-length cDNA clones and deep expressed sequence tag resources, obtained in Arabidopsis primarily after release of the complete genome, has been recognized by the rice genomics community. For rice >250,000 expressed sequence tags and 28,000 full-length cDNA sequences are available prior to the completion of the genome sequence. With respect to tools for Arabidopsis functional genomics, deep sequence-tagged lines, inexpensive spotted oligonucleotide arrays, and a near-complete whole genome Affymetrix array are publicly available. The development of similar functional genomics resources for rice is in progress that for the most part has been more streamlined based on lessons learned from Arabidopsis. Genomic resource development has been essential to set the stage for hypothesis-driven research, and Arabidopsis continues to provide paradigms for testing in rice to assess function across taxonomic divisions and in a crop species.

Arabidopsis↗
PubMed1998

The Environmental Genome Project: functional analysis of polymorphisms.

The ultimate goal of the Environmental Genome Project is the improvement of human health on the basis of information about the variations in certain genes. The first phase of the project will involve the selection of the human genes and characterization of the alleles occurring in the American population. However, intelligent use of this information will require analysis of the relevance of the allelic differences. Epidemiology alone will not solve the problem, and mechanistic studies will be required. Factors to be considered in the design of functional analyses are considered in this commentary.

Environmental Pollutants↗
PubMed2001

Sequence- and structure-based protein function prediction from genomic information.

Existing functional annotation transfer is fraught with inaccuracies that may hinder forward interpretation and mining of genomic data. Hand-curation of the annotation placed into databases is not practical. In lieu of experimental evidence, computational biological approaches offer high-throughput tools to predict function accurately; however, these methods are still notably deficient in defining and describing the complexity of protein function. Enriching genomic sequences obtained from sequencing efforts and expression array methods with protein function information and classification will be an efficient first step for incorporating genomic data into drug discovery programs.

Computational Biology↗
PubMed2026

The current and future perspective of ChickenGTEx project and its applications in precision breeding.

The Chicken Genotype-Tissue Expression (ChickenGTEx) project was established to systematically characterize the regulatory landscape of the chicken genome and to accelerate the translation of functional genomics into precision breeding. By integrating whole-genome sequencing with multi-tissue transcriptomic profiling, ChickenGTEx provides a comprehensive atlas of gene expression regulation across diverse tissues and physiological systems. Current findings demonstrate that complex production traits are governed by coordinated regulatory networks rather than isolated loci, with substantial contributions from tissue-specific gene expression, structural variation, and genotype-by-sex interactions. Sex-dependent regulatory effects further refine the genetic architecture of metabolic, immune, and reproductive traits, highlighting the importance of incorporating sex as a biological variable in genomic analyses. Application of integrative omics frameworks within elite layer populations has revealed multilayer regulatory mechanisms underlying extended laying performance, feed efficiency, metabolic health, and eggshell quality. By partitioning phenotypic variance into genetic, regulatory, and host-microbiome components, these approaches move beyond association-based mapping toward causal inference and biological interpretation. Importantly, validated regulatory loci identified through ChickenGTEx and related analyses provide actionable markers for genomic selection and rational targets for precision genome modification. Looking forward, continued expansion of regulatory atlases, incorporation of single-cell and longitudinal data in diverse environmental conditions, and integration of functional annotation into breeding pipelines will further enhance prediction accuracy and sustainable genetic improvement. The ChickenGTEx project thus represents a foundational platform bridging functional genomics and practical poultry breeding.

Animals↗
PubMed2006

Excisable cassettes: new tools for functional analysis of Streptomyces genomes.

The functional analysis of microbial genomes often requires gene inactivation. We constructed a set of cassettes consisting of single antibiotic resistance genes flanked by the attL and attR sites resulting from site-specific integration of the Streptomyces pSAM2 element. These cassettes can easily be used to inactivate genes by in-frame deletion in Streptomyces by a three-step strategy. In the first step, in Escherichia coli, the cassette is inserted into a cloned copy of the gene to be inactivated. In the second step, the gene is replaced by homologous recombination in Streptomyces, allowing substitution of the wild-type target gene with its inactivated counterpart. In the third step, the cassette can be removed by expression of the pSAM2 genes xis and int. The resulting strains are marker-free and contain an "attB-like" sequence of 33, 34, or 35 bp with no stop codon if the cassette is correctly chosen. Thus, a gene can be disrupted by creating an in-frame deletion, avoiding polar effects if downstream genes are cotranscribed with the target gene. A set of cassettes was constructed to contain a hygromycin or gentamicin resistance gene flanked by the attL and attR sites. The initial constructions carrying convenient cloning sites allow the insertion of any other marker gene. We tested insertion and excision by inserting a cassette into orf3, the third gene of an operon involved in spiramycin biosynthesis. We verified that the cassette exerted a polar effect on the transcription of downstream genes but that, after excision, complementation with orf3 alone restored spiramycin production.

Attachment Sites, Microbiological↗
PubMed2004

Comparative genomics for reliable protein-function prediction from genomic data.

Genomic data provide invaluable, yet unreliable information about protein function. However, if the overlap in information among various genomic datasets is taken into account, one observes an increase in the reliability of the protein-function predictions that can be made. Recently published approaches achieved this either by comparing the same type of data from multiple species (horizontal comparative genomics) or by using subtle, Bayesian methods to compare different types of genomic data from a single species (vertical comparative genomics). In this article, we discuss these methods, illustrating horizontal comparative genomics by comparing yeast two-hybrid (Y2H) data from Saccharomyces cerevisiae with Y2H data from Drosophila melanogaster, and illustrating vertical comparative genomics by comparing RNA expression data with proteomic data from Plasmodium falciparum.

Animals↗
PubMed2000

Functional and genomic analysis of the human mitochondrial intermediate peptidase, a putative protein partner of frataxin.

We showed recently that the yeast mitochondrial intermediate peptidase (YMIP polypeptide; gene symbol, OCT1) promotes mitochondrial iron uptake by catalyzing the maturation of iron-utilizing proteins and exacerbates the mitochondrial iron accumulation that results from loss of yeast frataxin, a mitochondrial protein required for mitochondrial iron efflux. This suggests that the human MIP (HMIP polypeptide; gene symbol MIPEP) may be one of the loci predicted to influence the clinical manifestations of Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative disease caused by lack of human frataxin. To begin to test this hypothesis, we have characterized HMIP at the functional and genomic levels. We show that HMIP can complement a yeast knock-out mutant lacking YMIP, demonstrating that HMIP and YMIP are functional homologues. The MIPEP gene spans 57 kb and consists of 19 exons that correlate with the functional domains of HMIP. Primer extension analysis has identified a major transcript of the MIPEP gene expressed differentially and predominantly in tissues with high oxygen consumption, while sequence analysis of approximately 2 kb of 5'-flanking DNA has revealed putative Mt1/3/4, NF-kappaB, and AP-1 elements that may regulate MIPEP expression in these tissues. Using a new polymorphic (CA)(n) repeat in intron 4, MIPEP has been genetically mapped within a 7-cM interval between markers D13S283 and D13S217 on 13q12. This work provides the basis for molecular analysis of MIPEP in FRDA and possibly other neurodegenerative diseases.

Base Sequence↗
PubMed2005

Identification of the Wnt signaling activator leucine-rich repeat in Flightless interaction protein 2 by a genome-wide functional analysis.

The Wnt signaling pathway acts ubiquitously in metazoans to control various aspects of embryonic development. Wnt ligands bind their receptors Frizzled and low-density lipoprotein receptor-related protein 5/6 and function through Disheveled (Dvl), Axin, adenomatous polyposis coli, glycogen synthase kinase 3beta, and casein kinase (CK) 1 to stabilize beta-catenin and induce lymphocyte enhancer-binding factor (LEF)/T cell factor (TCF)-dependent transcriptional activities. To identify previously unrecognized Wnt signaling modulators, a genome-wide functional screen was performed using large-scale arrayed cDNA collections. From this screen, both known components and previously uncharacterized regulators of this pathway were identified, including beta-catenin, Dvl1, Dvl3, Fbxw-1, Cul1, CK1epsilon, CK1delta, and gamma-catenin. In particular, a previously unrecognized activator, LRRFIP2 (leucine-rich repeat in Flightless interaction protein 2), was found that interacts with Dvl to increase the cellular levels of beta-catenin and activate beta-catenin/LEF/TCF-dependent transcriptional activity. The function of LRRFIP2 is blocked when a dominant negative Dvl (Xdd1) is coexpressed. Expression of LRRFIP2 in Xenopus embryos induced double axis formation and Wnt target gene expression; a dominant negative form of LRRFIP2 suppresses ectopic Wnt signaling in Xenopus embryos and partially inhibits endogenous dorsal axis formation. These data suggest that LRRFIP2 plays an important role in transducing Wnt signals.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Functional genomics-based studies of the microbial ecology of hyperthermophilic micro-organisms.

Although much attention has been paid to the genetic, biochemical and physiological aspects of individual hyperthermophiles, how these unique micro-organisms relate to each other and to their natural habitats must be addressed in order to develop a comprehensive understanding of life at high temperatures. Phylogenetic 16 S rRNA-based profiling of samples from various geothermal sites has provided insights into community structure, but this must be complemented with efforts to relate metabolic strategies to biotic and abiotic characteristics in high-temperature habitats. Described here are functional genomics-based approaches, using cDNA microarrays, to gain insight into how ecological features such as biofilm formation, species interaction, and possibly even gene transfer may occur in native environments, as well as to determine what genes or sets of genes may be tied to environmental functionality.

Biofilms↗
PubMed2004

Form follows function: The genomic organization of cellular differentiation.

The extent to which the nucleus is functionally organized has broad biological implications. Evidence supports the idea that basic nuclear functions, such as transcription, are structurally integrated within the nucleus. Moreover, recent studies indicate that the linear arrangement of genes within eukaryotic genomes is nonrandom. We suggest that determining the relationship between nuclear organization and the linear arrangement of genes will lead to a greater understanding of how transcriptomes, dedicated to a particular cellular function or fate, are coordinately regulated. Current network theories may provide a useful framework for modeling the inherent complexity the functional organization of the nucleus.

Animals↗
PubMed2005

Genomic and functional delineation of dendritic cells and memory T cells derived from grass pollen-allergic patients and healthy individuals.

Dendritic cells (DCIs) possess a potent ability to modulate and activate specific T-cell responses to allergens, which play a pivotal role in allergic inflammation by secreting cytokines and other mediators. However, the molecular mechanisms by which allergen-challenged DCs regulate specific T-cell responses are still not well characterized. This study aims at elucidating the molecular mechanisms underlying the DC-T-cell interaction during an allergic immune response to grass pollen, using a genomic and functional approach. Transcriptional analysis was performed on grass allergen Phleum pratense-stimulated DCs and on autologous memory CD4(+) T cells co-cultured with allergen-challenged DCs from healthy and allergic donors. DCs from the allergic donors were potent inducers of T-cell proliferation and T(h)2 polarization, as demonstrated by high IL-4, IL-5 and IL-13, and low IFN-gamma production. A gradual up-regulation of activation markers on both DCs and T cells was evident during the co-culture period, demonstrating an educational element of the DC-T-cell interaction. The global transcriptional analysis revealed a differential gene regulation in DCs and T cells derived from allergic donors after stimulation with allergen, as compared with the healthy donors. Peripheral memory CD4(+) T cells from healthy and allergic donors also responded differently after stimulation with allergen-loaded DCs with respect to cytokine production, proliferation, surface marker expression and gene transcription. We found up-regulated genes involved in T(h)2 cell biology, such as genes important for homing, adhesion, signaling and transcription, in addition to genes previously not described in the context of allergy. The panel of differentially expressed genes in the allergic group will form the basis for an increased understanding of the molecular mechanisms in allergy.

Biomarkers↗
PubMed1991

Human genome protein function database.

A database which focuses on the normal functions of the currently-known protein products of the Human Genome was constructed. Information is stored as text, figures, tables, and diagrams. The program contains built-in functions to modify, update, categorize, hypertext, search, create reports, and establish links to other databases. The semi-automated categorization feature of the database program was used to classify these proteins in terms of biomedical functions.

Databases, Factual↗
PubMedDate not supplied

Post-genomic virology: the impact of bioinformatics, microarrays and proteomics on investigating host and pathogen interactions.

Post-genomic research encompasses many diverse aspects of modern science. These include the two broad subject areas of computational biology (bioinformatics) and functional genomics. Laboratory based functional genomics aims to measure and assess either the messenger RNA (mRNA) levels (transcriptome studies) or the protein content (proteome studies) of cells and tissues. All of these methods have been applied recently to the study of host and pathogen interactions for both bacteria and viruses. A basic overview of the technology is given in this review together with approaches to data analysis. The wealth of information produced from even these preliminary studies has shown the generalities, subtleties and specificities of host-pathogen interactions. Such research should ultimately result in new methods for diagnosing and treating infectious diseases.

Amino Acid Sequence↗
PubMed2004

Microarray expression analyses of Arabidopsis guard cells and isolation of a recessive abscisic acid hypersensitive protein phosphatase 2C mutant.

Oligomer-based DNA Affymetrix GeneChips representing about one-third of Arabidopsis (Arabidopsis thaliana) genes were used to profile global gene expression in a single cell type, guard cells, identifying 1309 guard cell-expressed genes. Highly pure preparations of guard cells and mesophyll cells were isolated in the presence of transcription inhibitors that prevented induction of stress-inducible genes during cell isolation procedures. Guard cell expression profiles were compared with those of mesophyll cells, resulting in identification of 64 transcripts expressed preferentially in guard cells. Many large gene families and gene duplications are known to exist in the Arabidopsis genome, giving rise to redundancies that greatly hamper conventional genetic and functional genomic analyses. The presented genomic scale analysis identifies redundant expression of specific isoforms belonging to large gene families at the single cell level, which provides a powerful tool for functional genomic characterization of the many signaling pathways that function in guard cells. Reverse transcription-PCR of 29 genes confirmed the reliability of GeneChip results. Statistical analyses of promoter regions of abscisic acid (ABA)-regulated genes reveal an overrepresented ABA responsive motif, which is the known ABA response element. Interestingly, expression profiling reveals ABA modulation of many known guard cell ABA signaling components at the transcript level. We further identified a highly ABA-induced protein phosphatase 2C transcript, AtP2C-HA, in guard cells. A T-DNA disruption mutation in AtP2C-HA confers ABA-hypersensitive regulation of stomatal closing and seed germination. The presented data provide a basis for cell type-specific genomic scale analyses of gene function.

Abscisic Acid↗
PubMed2000

Genomic and functional changes induced by the activation of the peripheral cannabinoid receptor CB2 in the promyelocytic cells HL-60. Possible involvement of the CB2 receptor in cell differentiation.

The function of the peripheral cannabinoid receptor (CB2), which is mainly expressed on hematopoietic cells, remains an enigma. In an attempt to decipher its role, we used Affymetrix DNA chips to investigate the gene expression profile of the promyelocytic cells HL-60 transfected with the CB2 receptor and activated with the cannabinoid agonist CP 55,940. Agonist exposure of these cells led to an activation of a mitogen-activated protein kinase cascade and a receptor desensitization, indicating a functional coupling of the transfected receptors. At the genomic level, activation of the CB2 receptors induced an up-regulation of nine genes involved in cytokine synthesis, regulation of transcription, and cell differentiation. A majority of them are under the control of the transcription factor NF-kappaB, whose nuclear translocation was demonstrated. Many features of the transcriptional events, reported here for the first time, appeared to be related to an activation of a cell differentiation program, suggesting that CB2 receptors could play a role in the initialization of cell maturation. Moreover, we showed that CB2-activated wild-type HL-60 cells developed properties usually found in host defense effector cells such as an enhanced release of chemotactic cytokines and an increased motility, characteristic of more mature cells of the granulocytic-monocytic lineage.

Camphanes↗
PubMed2001

Sequence variation and disease in the wake of the draft human genome.

The sequencing phase of the human genome project will soon be over. In its wake, repertoires of sequence polymorphisms among the human population are being sampled and a battery of functional genomics projects, from gene and protein expression studies to whole proteome interaction experiments, are generating vast quantities of data. Now that the data, or the means to generate data, are available it is the application of this information in enhancing our understanding of biology that represents the next formidable challenge. Two prominent issues should be considered. First, existing data must be analysed using the best methods available. The prediction of enzymatic activity for bestrophin, whose gene is mutated in Best macular dystrophy, is described in this review. This is an example of the experimentally testable hypotheses that can result from such detailed and exhaustive analyses. Secondly, the torrents of data from high-throughput studies will need to be made more accessible to all using web-based resources that integrate and digest complementary data types. The internet sites that showcase the human genome sequence are blazing a new trail. Ultimately, the success of genome sequencing and functional genomics will be measured not by the quantity and accuracy of raw data generated, but how rapidly they can be harnessed to span the divide between genotype and phenotype.

Alleles↗