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At least 919 records · Page 51Linked to original sources
PubMed2006

One billion years of bZIP transcription factor evolution: conservation and change in dimerization and DNA-binding site specificity.

The genomic era has revealed that the large repertoire of observed animal phenotypes is dependent on changes in the expression patterns of a finite number of genes, which are mediated by a plethora of transcription factors (TFs) with distinct specificities. The dimerization of TFs can also increase the complexity of a genetic regulatory network manifold, by combining a small number of monomers into dimers with distinct functions. Therefore, studying the evolution of these dimerizing TFs is vital for understanding how complexity increased during animal evolution. We focus on the second largest family of dimerizing TFs, the basic-region leucine zipper (bZIP), and infer when it expanded and how bZIP DNA-binding and dimerization functions evolved during the major phases of animal evolution. Specifically, we classify the metazoan bZIPs into 19 families and confirm the ancient nature of at least 13 of these families, predating the split of the cnidaria. We observe fixation of a core dimerization network in the last common ancestor of protostomes-deuterostomes. This was followed by an expansion of the number of proteins in the network, but no major dimerization changes in interaction partners, during the emergence of vertebrates. In conclusion, the bZIPs are an excellent model with which to understand how DNA binding and protein interactions of TFs evolved during animal evolution.

Animals↗
PubMed2006

Novel function of ovarian growth factors: combined studies by DNA microarray, biochemical and physiological approaches.

Owing to the development of the DNA microarray technique, modulation of gene function can be studied systematically. Considerable attention has been focused on members of the growth factor family to elucidate the main regulators of oocyte maturation and ovarian follicle rupture. Among these growth factors, it was found both in rodents and in humans that amphiregulin (Ar) and epiregulin (Ep) of the epidermal growth factor (EGF) family were dramatically up-regulated by gonadotrophins in the intact ovary and in primary granulosa cells, respectively. Their role in cumulus expansion and oocyte maturation was established in rodents, and their formation under LH stimulation in granulosa cells was demonstrated in humans. To be activated, Ar and Ep must be cleaved by A Disintegrin And Metalloproteinases (ADAMs) family. However, the precise processing of Ar and Ep by the cumulus cells is still obscure. Future investigations using DNA microarray technique may reveal the repertoire of genes activated in Ar- and Ep-stimulated cumulus cells and may help elucidate the molecular basis of ovulation.

Amphiregulin↗
PubMed1999

The Eukaryotic Promoter Database (EPD): recent developments.

The Eukaryotic Promoter Database (EPD) is an annotated non-redundant collection of eukaryotic POL II promoters, for which the transcription start site has been determined experimentally. Access to promoter sequences is provided by pointers to positions in nucleotide sequence entries. The annotation part of an entry includes description of the initiation site mapping data, cross-references to other databases, and bibliographic references. EPD is structured in a way that facilitates dynamic extraction of biologically meaningful promoter subsets for comparative sequence analysis. Recent efforts have focused on exhaustive cross-referencing to the EMBL nucleotide sequence database, and on the improvement of the WWW-based user interfaces and data retrieval mechanisms. EPD can be accessed at http://www.epd.isb-sib.ch

Algorithms↗
PubMed2000

The eukaryotic promoter database (EPD).

The Eukaryotic Promoter Database (EPD) is an annotated non-redundant collection of eukaryotic POL II promoters for which the transcription start site has been determined experimentally. Access to promoter sequences is provided by pointers to positions in nucleotide sequence entries. The annotation part of an entry includes a description of the initiation site mapping data, exhaustive cross-references to the EMBL nucleotide sequence database, SWISS-PROT, TRANSFAC and other databases, as well as bibliographic references. EPD is structured in a way that facilitates dynamic extraction of biologically meaningful promoter subsets for comparative sequence analysis. WWW-based interfaces have been developed that enable the user to view EPD entries in different formats, to select and extract promoter sequences according to a variety of criteria, and to navigate to related databases exploiting different cross-references. The EPD web site also features yearly updated base frequency matrices for major eukaryotic promoter elements. EPD can be accessed at http://www.epd.isb-sib.ch

Database Management Systems↗
PubMed2002

The Eukaryotic Promoter Database, EPD: new entry types and links to gene expression data.

The Eukaryotic Promoter Database (EPD) is an annotated, non-redundant collection of eukaryotic Pol II promoters, for which the transcription start site has been determined experimentally. Access to promoter sequences is provided by pointers to positions in nucleotide sequence entries. The annotation part of an entry includes a description of the initiation site mapping data, exhaustive cross-references to the EMBL nucleotide sequence database, SWISS-PROT, TRANSFAC and other databases, as well as bibliographic references. EPD is structured in a way that facilitates dynamic extraction of biologically meaningful promoter subsets for comparative sequence analysis. World Wide Web-based interfaces have been developed which enable the user to view EPD entries in different formats, to select and extract promoter sequences according to a variety of criteria, and to navigate to related databases exploiting different cross-references. The EPD web site also features yearly updated base frequency matrices for major eukaryotic promoter elements. EPD can be accessed at http://www.epd.isb-sib.ch.

Animals↗
PubMed2003

CADLIVE for constructing a large-scale biochemical network based on a simulation-directed notation and its application to yeast cell cycle.

The further understanding of the mechanisms of gene regulatory networks requires comprehensive tools for both the representation of complicated signal transduction pathways and the in silico identification of genomic signals that govern the regulation of gene expression. Consequently, sophisticated notation must be developed to represent the signal transduction pathways in a form that can be readily processed by both computers and humans. We propose the regulator-reaction equations combined with detailed attributes including the associated cellular component, molecular function, and biological process and present the simulation-directed graphical notation that is derived from modification of Kohn's method. We have developed the software suite, CADLIVE (Computer-Aided Design of LIVing systEms), which features a graphical user interface (GUI) to edit large-scale maps of complicated signal transduction pathways using a conventional XML-based representation. The regulator-reaction equations represent not only mechanistic reactions, but also semantic models containing ambiguous and incomplete processes. In order to demonstrate the feasibility of CADLIVE, we constructed a detailed map of the budding yeast cell cycle, which consists of 184 molecules and 152 reactions, in a really compact space. CADLIVE enables one to look at the whole view of a large-scale map, to integrate postgenomic data into the map, and to computationally simulate the signal transduction pathways, which greatly facilitates exploring novel or unexpected interactions.

Cell Cycle↗
PubMed2006

MvirDB--a microbial database of protein toxins, virulence factors and antibiotic resistance genes for bio-defence applications.

Knowledge of toxins, virulence factors and antibiotic resistance genes is essential for bio-defense applications aimed at identifying 'functional' signatures for characterizing emerging or engineered pathogens. Whereas genetic signatures identify a pathogen, functional signatures identify what a pathogen is capable of. To facilitate rapid identification of sequences and characterization of genes for signature discovery, we have collected all publicly available (as of this writing), organized sequences representing known toxins, virulence factors, and antibiotic resistance genes in one convenient database, which we believe will be of use to the bio-defense research community. MvirDB integrates DNA and protein sequence information from Tox-Prot, SCORPION, the PRINTS virulence factors, VFDB, TVFac, Islander, ARGO and a subset of VIDA. Entries in MvirDB are hyperlinked back to their original sources. A blast tool allows the user to blast against all DNA or protein sequences in MvirDB, and a browser tool allows the user to search the database to retrieve virulence factor descriptions, sequences, and classifications, and to download sequences of interest. MvirDB has an automated weekly update mechanism. Each protein sequence in MvirDB is annotated using our fully automated protein annotation system and is linked to that system's browser tool. MvirDB can be accessed at http://mvirdb.llnl.gov/.

Bacterial Proteins↗
PubMed2005

Cell-type-specific transcriptomics in chimeric models using transcriptome-based masks.

Regulatory networks involving different cell types control inflammation, morphogenesis and tissue homeostasis. Cell-type-specific transcriptional profiling offers a powerful tool for analyzing such cross-talk but is often hampered by mingling of cells within a tissue. Here, we present a novel method that performs cell-type-specific expression measurements without prior cell separation. This involves inter-species transplantation or chimeric co-culture models among which the human mouse system is frequently used. Here, we exploit the sufficiently divergent transcriptomes of human and mouse in conjunction with high-density oligonucleotide arrays. This required a masking procedure based on transcriptome databases and exhaustive fuzzy mapping of oligonucleotide probes onto these data. The approach was tested in a human-mouse experiment, demonstrating that we can efficiently measure species-specific transcriptional profiles in chimeric RNA samples without physically separating cells. Our results stress the importance of transcriptome databases with accurate 3' mRNA termination for computational prediction of accurate probe masks. We find that most human and mouse 3'-untranslated region contain unique stretches to allow for an effective control of cross-hybridization between the two species. This approach can be applied to xenograft models studying tumor-host interactions, morphogenesis or immune responses.

Animals↗
PubMed2004

Molecular psychiatry meeting, February 2003, Lake Louise, Canada.

The 10th Annual Molecular Psychiatry Conference was held in Lake Louise, Canada on 23-25 February 2003. The host was Bill Byerley (University of California, Irvine, California, USA), and the meeting was supported by Janssen Pharmaceutica and the Department of Psychiatry, University of California, Irvine, California, USA.

Anxiety Disorders↗
PubMed2006

Early diagnosis and predictors of malignancy of adnexal masses.

PURPOSE OF REVIEW: Ovarian cancer is an important cause of death among women with a malignant gynecological tumor. Cure rates for the disease at an early stage are around 80-90%, but survival is only 50% as the majority of women already show advanced disease upon diagnosis. The combination of gynecological examination, ultrasonography, and systemic tumor marker assay is considered to be a good strategy for the early diagnosis of ovarian neoplasia. RECENT FINDINGS: Today, new technologies such as ultrasonography and tumor marker assay have increased the diagnosis rate for adnexal masses. These non-invasive methods, however, frequently do not distinguish benign conditions from malignant ones, which results in unnecessary surgery. Transvaginal ultrasonography is useful for diagnosing adnexal masses, but benign and malignant adnexal masses can present similar morphological characteristics. Combination with color Doppler ultrasonography and/or tumor markers may improve the accuracy of the method. Gene-expression array, proteomics and mathematical models form new approaches, but proper prospective studies are needed to validate them. SUMMARY: The techniques of pelvic examination, ultrasonography, color Doppler ultrasonography, and tumor markers can be indicated for the diagnosis of ovarian cancer. The differentiation between benign and malignant ovarian tumor is, however, a clinical challenge. Until better diagnostic methods become available, patients and their physicians can use these techniques to decide on management.

Adnexal Diseases↗
PubMed2005

Nesting fidelity and molecular evidence for natal homing in the freshwater turtle, Graptemys kohnii.

Numerous studies of sea turtle nesting ecology have revealed that females exhibit natal homing, whereby they imprint on the nesting area from which they hatch and subsequently return there to nest as adults. Because freshwater turtles comprise the majority of reptiles known to display environmental sex determination (ESD), the study of natal homing in this group may shed light on recent evolutionary models of sex allocation that are predicated on natal homing in reptiles with ESD. We examined natal homing in Graptemys kohnii, a freshwater turtle with ESD, using mitochondrial sequencing, microsatellite genotyping and mark and recapture of 290 nesting females. Females showed high fidelity to nesting areas, even after being transplanted several kilometres away. A Mantel test revealed significant genetic isolation by distance with respect to nesting locations (r=0.147; p<0.05), suggesting that related females nest in close proximity to one another. The patterns of fidelity and genotype distributions are consistent with homing at a scale that may affect population sex ratios.

Animals↗
PubMed2003

Identification and characterization of novel pyoverdine synthesis genes in Pseudomonas aeruginosa.

Fluorescent pseudomonads secrete yellow-green siderophores named pyoverdines or pseudobactins. These comprise a dihydroxyquinoline derivative joined to a type-specific peptide and, usually, a carboxylic acid or amide. In Pseudomonas aeruginosa strain PAO1, six genes that encode proteins required for pyoverdine synthesis (pvd genes) have been identified previously. Expression of all of these genes requires an alternative sigma factor PvdS. The purpose of this research was to identify other genes that are required for pyoverdine synthesis in P. aeruginosa PAO1. Fourteen candidate genes were identified from the PAO1 genome sequence on the basis of their location in the genome, the functions of homologues in other bacteria, and whether their expression was likely to be PvdS-dependent. The candidate genes were mutated and the effects of the mutations on pyoverdine production were determined. Eight new pvd genes were identified. The presence of homologues of pvd genes in other strains of P. aeruginosa was determined by Southern blotting and in other fluorescent pseudomonads by interrogation of genome sequences. Five pvd genes were restricted to strains of P. aeruginosa that make the same pyoverdine as strain PAO1, suggesting that they direct synthesis of the type-specific peptide. The remaining genes were present in all strains of P. aeruginosa that were examined and homologues were present in other Pseudomonas species. These genes are likely to direct synthesis of the dihydroxyquinoline moiety and the attached carboxylic acid/amide group. It is likely that most if not all of the genes required for pyoverdine synthesis in P. aeruginosa PAO1 have now been identified and this will form the basis for a biochemical description of the pathway of pyoverdine synthesis.

Bacterial Proteins↗
PubMed2005

Plasmid p256 from Lactobacillus plantarum represents a new type of replicon in lactic acid bacteria, and contains a toxin-antitoxin-like plasmid maintenance system.

Lactobacillus plantarum NC7 harbours a single 7.2 kb plasmid called p256. This report describes the complete nucleotide sequence and annotation of p256, as well as the identification of the minimal replicon of the plasmid. Based on sequence features in the unusually small (0.7 kb) minimal replicon, and the absence of a gene for a replication-relevant protein, p256 seems to represent a hitherto unknown type of theta replicon in lactic acid bacteria (LAB), with a relatively low copy-number. In addition, a putative toxin-antitoxin (TA) locus was identified. Experiments with variants of p256 indicated that the TA system was involved in plasmid maintenance. Furthermore, controlled expression of the TA genes stabilized vectors derived from the p256 replicon. To the authors' knowledge, this is the first time a TA locus with a demonstrated plasmid maintenance function has been identified in LAB. Transformation of several LAB with plasmids derived from p256 indicated that it has a narrow host range. Several effective expression vectors based on the p256 replicon have been constructed.

Amino Acid Sequence↗
PubMed2004

Decoding randomly ordered DNA arrays.

We have developed a simple and efficient algorithm to identify each member of a large collection of DNA-linked objects through the use of hybridization, and have applied it to the manufacture of randomly assembled arrays of beads in wells. Once the algorithm has been used to determine the identity of each bead, the microarray can be used in a wide variety of applications, including single nucleotide polymorphism genotyping and gene expression profiling. The algorithm requires only a few labels and several sequential hybridizations to identify thousands of different DNA sequences with great accuracy. We have decoded tens of thousands of arrays, each with 1520 sequences represented at approximately 30-fold redundancy by up to approximately 50,000 beads, with a median error rate of <1 x 10(-4) per bead. The approach makes use of error checking codes and provides, for the first time, a direct functional quality control of every element of each array that is manufactured. The algorithm can be applied to any spatially fixed collection of objects or molecules that are associated with specific DNA sequences.

Algorithms↗
PubMed2003

DNA book.

We propose herein a new method of DNA distribution, whereby DNA clones or PCR products are printed directly onto the pages of books and delivered to users along with relevant scientific information. DNA sheets, comprising water-soluble paper onto which DNA is spotted, can be bound into books. Readers can easily extract the DNA fragments from DNA sheets and amplify them using PCR. We show that DNA sheets can withstand various conditions that may be experienced during bookbinding and delivery, such as high temperatures and humidity. Almost all genes (95%-100% of randomly selected RIKEN mouse cDNA clones) were recovered successfully by use of PCR. Readers can start their experiments after a 2-h PCR amplification without waiting for the delivery of DNA clones. The DNA Book thus provides a novel method for delivering DNA in a timely and cost-effective manner. A sample DNA sheet (carrying RIKEN mouse cDNA clones encoding genes of enzymes for the TCA cycle) is included in this issue for field-testing. We would greatly appreciate it if readers could attempt to extract DNA and report the results and whether the DNA sheet was shipped to readers in good condition.

Animals↗
PubMed2004

Accumulation of carotenoids and expression of carotenoid biosynthetic genes during maturation in citrus fruit.

The relationship between carotenoid accumulation and the expression of carotenoid biosynthetic genes during fruit maturation was investigated in three citrus varieties, Satsuma mandarin (Citrus unshiu Marc.), Valencia orange (Citrus sinensis Osbeck), and Lisbon lemon (Citrus limon Burm.f.). We cloned the cDNAs for phytoene synthase (CitPSY), phytoene desaturase (CitPDS), zeta-carotene (car) desaturase (CitZDS), carotenoid isomerase (CitCRTISO), lycopene beta-cyclase (CitLCYb), beta-ring hydroxylase (CitHYb), zeaxanthin (zea) epoxidase (CitZEP), and lycopene epsilon-cyclase (CitLCYe) from Satsuma mandarin, which shared high identities in nucleotide sequences with Valencia orange, Lisbon lemon, and other plant species. With the transition of peel color from green to orange, the change from beta,epsilon-carotenoid (alpha-car and lutein) accumulation to beta,beta-carotenoid (beta-car, beta-cryptoxanthin, zea, and violaxanthin) accumulation was observed in the flavedos of Satsuma mandarin and Valencia orange, accompanying the disappearance of CitLCYe transcripts and the increase in CitLCYb transcripts. Even in green fruit, high levels of beta,epsilon-carotenoids and CitLCYe transcripts were not observed in the juice sacs. As fruit maturation progressed in Satsuma mandarin and Valencia orange, a simultaneous increase in the expression of genes (CitPSY, CitPDS, CitZDS, CitLCYb, CitHYb, and CitZEP) led to massive beta,beta-xanthophyll (beta-cryptoxanthin, zea, and violaxanthin) accumulation in both the flavedo and juice sacs. The gene expression of CitCRTISO was kept low or decreased in the flavedo during massive beta,beta-xanthophyll accumulation. In the flavedo of Lisbon lemon and Satsuma mandarin, massive accumulation of phytoene was observed with a decrease in the transcript level for CitPDS. Thus, the carotenoid accumulation during citrus fruit maturation was highly regulated by the coordination of the expression among carotenoid biosynthetic genes. In this paper, the mechanism leading to diversity in beta,beta-xanthophyll compositions between Satsuma mandarin and Valencia orange was also discussed on the basis of the substrate specificity of beta-ring hydroxylase and the balance of expression between upstream synthesis genes (CitPSY, CitPDS, CitZDS, and CitLCYb) and downstream synthesis genes (CitHYb and CitZEP).

Alkyl and Aryl Transferases↗
PubMedDate not supplied

Constructing and analyzing a large-scale gene-to-gene regulatory network--lasso-constrained inference and biological validation.

We construct a gene-to-gene regulatory network from time-series data of expression levels for the whole genome of the yeast Saccharomyces cerevisae, in a case where the number of measurements is much smaller than the number of genes in the network. This network is analyzed with respect to present biological knowledge of all genes (according to the Gene Ontology database), and we find some of its large-scale properties to be in accordance with known facts about the organism. The linear modeling employed here has been explored several times, but due to lack of any validation beyond investigating individual genes, it has been seriously questioned with respect to its applicability to biological systems. Our results show the adequacy of the approach and make further investigations of the model meaningful.

Algorithms↗