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1

Ets oncogene-related gene Elg functions in Drosophila oogenesis.  

PubMed Central

Members of the ets gene family encode transcription factors that regulate the expression of a variety of cellular and viral genes including several protooncogenes. We have utilized Drosophila to elucidate the in vivo function of one family member. We show by complementation rescue and sequence analysis that the female sterile mutant tiny eggs (tne) is an allele of the Drosophila Ets-related gene Elg (also called D-elg). The mutation of a highly conserved tyrosine residue in the ETS DNA-binding domain of the Elg gene product demonstrates that normal gene function is required for proper follicle cell migration, chorion formation, and nurse cell-chromosome decondensation during Drosophila oogenesis. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5

Schulz, R A; The, S M; Hogue, D A; Galewsky, S; Guo, Q

1993-01-01

2

Transcription of functionally related constitutive genes is not coordinated.  

PubMed

Expression of an individual gene can vary considerably among genetically identical cells because of stochastic fluctuations in transcription. However, proteins comprising essential complexes or pathways have similar abundances and lower variability. It is not known whether coordination in the expression of subunits of essential complexes occurs at the level of transcription, mRNA abundance or protein expression. To directly measure the level of coordination in the expression of genes, we used highly sensitive fluorescence in situ hybridization (FISH) to count individual mRNAs of functionally related and unrelated genes within single Saccharomyces cerevisiae cells. Our results revealed that transcript levels of temporally induced genes are highly correlated in individual cells. In contrast, transcription of constitutive genes encoding essential subunits of complexes is not coordinated because of stochastic fluctuations. The coordination of these functional complexes therefore must occur post-transcriptionally, and likely post-translationally. PMID:21131977

Gandhi, Saumil J; Zenklusen, Daniel; Lionnet, Timothée; Singer, Robert H

2010-12-05

3

Functional modules by relating protein interaction networks and gene expression  

Microsoft Academic Search

Genes and proteins are organized on the basis of their particular mutual relations or according to their interactions in cellular and genetic networks. These include metabolic or signaling pathways and protein interaction, regulatory or co-expression net- works. Integrating the information from the different types of networks may lead to the notion of a func- tional network and functional modules. To

Sabine Tornow; H. W. Mewes

2003-01-01

4

miRNA-Mediated Functional Changes through Co-Regulating Function Related Genes  

Microsoft Academic Search

BackgroundmicroRNAs play important roles in various biological processes involving fairly complex mechanism. Analysis of genome-wide miRNA microarray demonstrate that a single miRNA can regulate hundreds of genes, but the regulative extent on most individual genes is surprisingly mild so that it is difficult to understand how a miRNA provokes detectable functional changes with such mild regulation.ResultsTo explore the internal mechanism

Jie He; Jin-Fang Zhang; Can Yi; Qing Lv; Wei-Dong Xie; Jian-Na Li; Gang Wan; Kai Cui; Hsiang-Fu Kung; Jennifer Yang; Burton B. Yang; Yaou Zhang; Fatah Kashanchi

2010-01-01

5

Dynamic resolution of functionally related gene sets in response to acute heat stress  

Microsoft Academic Search

BACKGROUND: Using a gene clustering strategy we determined intracellular pathway relationships within skeletal myotubes in response to an acute heat stress stimuli. Following heat shock, the transcriptome was analyzed by microarray in a temporal fashion to characterize the dynamic relationship of signaling pathways. RESULTS: Bioinformatics analyses exposed coordination of functionally-related gene sets, depicting mechanism-based responses to heat shock. Protein turnover-related

Joseph D Szustakowski; Penelope A Kosinski; Christine A Marrese; Jee-Hyung Lee; Stephen J Elliman; Nanguneri Nirmala; Daniel M Kemp

2007-01-01

6

Screening of osteoprotegerin-related feature genes in osteoporosis and functional analysis with DNA microarray  

PubMed Central

Background Osteoporosis affects 200 million people worldwide and places an enormous economic burden on society. We aim to identify the feature genes that are related to osteoprotegerin in osteoporosis and to perform function analysis with DNA microarray from human bone marrow. Methods We downloaded the gene expression profile GSE35957 from Gene Expression Omnibus database including nine gene chips from bone marrow mesenchymal stem cells of five osteoporotic and four non-osteoporotic subjects. The differentially expressed genes between normal and disease samples were identified by LIMMA package in R language. The interactions among the osteoprotegerin gene (OPG) and differentially expressed genes were searched and visualized by Cytoscape. MCODE and Bingo were used to perform module analysis. Finally, GENECODIS was used to obtain enriched pathways of genes in an interaction network. Results A total of 656 genes were identified as differentially expressed genes between osteoporotic and non-osteoporotic samples. IL17RC, COL1A1, and ESR1 were identified to interact with OPG directly from the protein-protein interaction network. A module containing ERS1 was screened out, and this module was most significantly enriched in organ development. Pathway enrichment analysis suggested genes in the interaction network were related to focal adhesion. Conclusions The expression pattern of IL17RC, COL1A1, and ESR1 can be useful in osteoporosis detection, which may help in identifying those populations at high risk for osteoporosis, and in directing treatment of osteoporosis.

2013-01-01

7

Regulation of Langerhans cell function by nerves containing calcitonin gene-related peptide  

Microsoft Academic Search

SEVERAL observations suggest interactions between the immune and nervous systems1,2. Psoriasis and atopic dermatitis may worsen with anxiety and have been associated with anomalous neuropeptide regulation2. Neurotransmitters affect lymphocyte function1-4 and lymphoid organs are innervated5-9. Calcitonin gene-related peptide (CGRP) is a neuropeptide and vasodilator10 that modulates some macrophage functions, including antigen presentation in vitro11. CGRP is associated with Langerhans cells

J. Hosoi; G. F. Murphy; C. L. Egan; E. A. Lerner; S. Grabbe; A. Asahina; R. D. Granstein

1993-01-01

8

Relating gene expression data on two-component systems to functional annotations in Escherichia coli  

PubMed Central

Background Obtaining physiological insights from microarray experiments requires computational techniques that relate gene expression data to functional information. Traditionally, this has been done in two consecutive steps. The first step identifies important genes through clustering or statistical techniques, while the second step assigns biological functions to the identified groups. Recently, techniques have been developed that identify such relationships in a single step. Results We have developed an algorithm that relates patterns of gene expression in a set of microarray experiments to functional groups in one step. Our only assumption is that patterns co-occur frequently. The effectiveness of the algorithm is demonstrated as part of a study of regulation by two-component systems in Escherichia coli. The significance of the relationships between expression data and functional annotations is evaluated based on density histograms that are constructed using product similarity among expression vectors. We present a biological analysis of three of the resulting functional groups of proteins, develop hypotheses for further biological studies, and test one of these hypotheses experimentally. A comparison with other algorithms and a different data set is presented. Conclusion Our new algorithm is able to find interesting and biologically meaningful relationships, not found by other algorithms, in previously analyzed data sets. Scaling of the algorithm to large data sets can be achieved based on a theoretical model.

Denton, Anne M; Wu, Jianfei; Townsend, Megan K; Sule, Preeti; Pruss, Birgit M

2008-01-01

9

The Ash-1, Ash-2 and Trithorax Genes of Drosophila Melanogaster Are Functionally Related  

PubMed Central

Mutations in the ash-1 and ash-2 genes of Drosophila melanogaster cause a wide variety of homeotic transformations that are similar to the transformations caused by mutations in the trithorax gene. Based on this similar variety of transformations, it was hypothesized that these genes are members of a functionally related set. Three genetic tests were employed here to evaluate that hypothesis. The first test was to examine interactions of ash-1, ash-2 and trithorax mutations with each other. Double and triple heterozygotes of recessive lethal alleles express characteristic homeotic transformations. For example, double heterozygotes of a null allele of ash-1 and a deletion of trithorax have partial transformations of their first and third legs to second legs and of their halteres to wings. The penetrance of these transformations is reduced by a duplication of the bithorax complex. The second test was to examine interactions with a mutation in the female sterile (1) homeotic gene. The penetrance of the homeotic phenotype in progeny from mutant mothers is increased by heterozygosis for alleles of ash-1 or ash-2 as well as for trithorax alleles. The third test was to examine the interaction with a mutation of the Polycomb gene. The extra sex combs phenotype caused by heterozygosis for a deletion of Polycomb is suppressed by heterozygosis for ash-1, ash-2 or trithorax alleles. The fact that mutations in each of the three genes gave rise to similar results in all three tests represents substantial evidence that ash-1, ash-2 and trithorax are members of a functionally related set of genes.

Shearn, A.

1989-01-01

10

Developmental and functional expression of miRNA-stability related genes in the nervous system.  

PubMed

In the nervous system, control of gene expression by microRNAs (miRNAs) has been investigated in fundamental processes, such as development and adaptation to ambient demands. The action of these short nucleotide sequences on specific genes depends on intracellular concentration, which in turn reflects the balance of biosynthesis and degradation. Whereas mechanisms underlying miRNA biogenesis has been investigated in recent studies, little is known about miRNA-stability related proteins. We first detected two genes in the retina that have been associated to miRNA stability, XRN2 and PAPD4. These genes are highly expressed during retinal development, however with distinct subcellular localization. We investigated whether these proteins are regulated during specific phases of the cell cycle. Combined analyses of nuclei position in neuroblastic layer and labeling using anti-cyclin D1 revealed that both proteins do not accumulate in S or M phases of the cell cycle, being poorly expressed in progenitor cells. Indeed, XRN2 and PAPD4 were observed mainly after neuronal differentiation, since low expression was also observed in astrocytes, endothelial and microglial cells. XRN2 and PAPD4 are expressed in a wide variety of neurons, including horizontal, amacrine and ganglion cells. To evaluate the functional role of both genes, we carried out experiments addressed to the retinal adaptation in response to different ambient light conditions. PAPD4 is upregulated after 3 and 24 hours of dark- adaptation, revealing that accumulation of this protein is governed by ambient light levels. Indeed, the fast and functional regulation of PAPD4 was not related to changes in gene expression, disclosing that control of protein levels occurs by post-transcriptional mechanisms. Furthermore, we were able to quantify changes in PAPD4 in specific amacrine cells after dark -adaptation, suggesting for circuitry-related roles in visual perception. In summary, in this study we first described the ontogenesis and functional expression of these two miRNA-stability related proteins in the retina. PMID:23700402

de Sousa, Érica; Walter, Lais Takata; Higa, Guilherme Shigueto Vilar; Casado, Otávio Augusto Nocera; Kihara, Alexandre Hiroaki

2013-05-20

11

Definition of historical models of gene function and their relation to students' understanding of genetics  

NASA Astrophysics Data System (ADS)

Models are often used when teaching science. In this paper historical models and students’ ideas about genetics are compared. The historical development of the scientific idea of the gene and its function is described and categorized into five historical models of gene function. Differences and similarities between these historical models are made explicit. Internal and external consistency problems between the models are identified and discussed. From the consistency analysis seven epistemological features are identified. The features vary in such ways between the historical models that it is claimed that learning difficulties might be the consequence if these features are not explicitly addressed when teaching genetics. Students’ understanding of genetics, as described in science education literature, is then examined. The comparison shows extensive parallelism between students’ alternative understanding of genetics and the epistemological features, i.e., the claim is strengthened. It is also argued that, when teaching gene function, the outlined historical models could be useful in a combined nature of science and history of science approach. Our findings also raise the question what to teach in relation to preferred learning outcomes in genetics.

Gericke, Niklas Markus; Hagberg, Mariana

2007-08-01

12

Transcriptional and functional studies of Acidithiobacillus ferrooxidans genes related to survival in the presence of copper.  

PubMed

The acidophilic Acidithiobacillus ferrooxidans can resist exceptionally high copper (Cu) concentrations. This property is important for its use in biomining processes, where Cu and other metal levels range usually between 15 and 100 mM. To learn about the mechanisms that allow A. ferrooxidans cells to survive in this environment, a bioinformatic search of its genome showed the presence of at least 10 genes that are possibly related to Cu homeostasis. Among them are three genes coding for putative ATPases related to the transport of Cu (A. ferrooxidans copA1 [copA1(Af)], copA2(Af), and copB(Af)), three genes related to a system of the resistance nodulation cell division family involved in the extraction of Cu from the cell (cusA(Af), cusB(Af), and cusC(Af)), and two genes coding for periplasmic chaperones for this metal (cusF(Af) and copC(Af)). The expression of most of these open reading frames was studied by real-time reverse transcriptase PCR using A. ferrooxidans cells adapted for growth in the presence of high concentrations of Cu. The putative A. ferrooxidans Cu resistance determinants were found to be upregulated when this bacterium was exposed to Cu in the range of 5 to 25 mM. These A. ferrooxidans genes conferred to Escherichia coli a greater Cu resistance than wild-type cells, supporting their functionality. The results reported here and previously published data strongly suggest that the high resistance of the extremophilic A. ferrooxidans to Cu may be due to part or all of the following key elements: (i) a wide repertoire of Cu resistance determinants, (ii) the duplication of some of these Cu resistance determinants, (iii) the existence of novel Cu chaperones, and (iv) a polyP-based Cu resistance system. PMID:19666734

Navarro, Claudio A; Orellana, Luis H; Mauriaca, Cecilia; Jerez, Carlos A

2009-08-07

13

Are "functionally related polymorphisms" of renin-angiotensin-aldosterone system gene polymorphisms associated with hypertension?  

PubMed Central

Background Genotype-phenotype association studies are typically based upon polymorphisms or haplotypes comprised of multiple polymorphisms within a single gene. It has been proposed that combinations of polymorphisms in distinct genes, which functionally impact the same phenotype, may have stronger phenotype associations than those within a single gene. We have tested this hypothesis using genes encoding components of the renin-angiotensin-aldosterone system and the high blood pressure phenotype. Methods Our analysis is based on 1379 participants of the cross-sectional SUNSET study randomly selected from the population register of Amsterdam. Each subject was genotyped for the angiotensinogen M235T, the angiotensin-converting enzyme insertion/deletion and the angiotensin II type 1 receptor A1166C polymorphism. The phenotype high blood pressure was defined either as a categorical variable comparing hypertension versus normotension as in most previous studies or as a continuous variable using systolic, diastolic and mean blood pressure in a multiple regression analysis with gender, ethnicity, age, body-mass-index and antihypertensive medication as covariates. Results Genotype-phenotype relationships were explored for each polymorphism in isolation and for double and triple polymorphism combinations. At the single polymorphism level, only the A allele of the angiotensin II type 1 receptor was associated with a high blood pressure phenotype. Using combinations of polymorphisms of two or all three genes did not yield stronger/more consistent associations. Conclusions We conclude that combinations of physiologically related polymorphisms of multiple genes, at least with regard to the renin-angiotensin-aldosterone system and the hypertensive phenotype, do not necessarily offer additional benefit in analyzing genotype/phenotype associations.

2010-01-01

14

Definition of Historical Models of Gene Function and Their Relation to Students' Understanding of Genetics  

ERIC Educational Resources Information Center

Models are often used when teaching science. In this paper historical models and students' ideas about genetics are compared. The historical development of the scientific idea of the gene and its function is described and categorized into five historical models of gene function. Differences and similarities between these historical models are made…

Gericke, Niklas Markus; Hagberg, Mariana

2007-01-01

15

Functional Redundancy and Divergence within the Arabidopsis RETICULATA-RELATED Gene Family1[W][OA  

PubMed Central

A number of Arabidopsis (Arabidopsis thaliana) mutants exhibit leaf reticulation, having green veins that stand out against paler interveinal tissues, fewer cells in the interveinal mesophyll, and normal perivascular bundle sheath cells. Here, to examine the basis of leaf reticulation, we analyzed the Arabidopsis RETICULATA-RELATED (RER) gene family, several members of which cause leaf reticulation when mutated. Although transcripts of RE, RER1, and RER3 were mainly detected in the bundle sheath cells of expanded leaves, functional RER3:GREEN FLUORESCENT PROTEIN was visualized in the chloroplast membranes of all photosynthetic cells. Leaf reticulation in the re and rer3 loss-of-function mutants occurred, along with accumulation of reactive oxygen species, in a photoperiod-dependent manner. A comparison of re and rer3 leaf messenger RNA expression profiles showed more than 200 genes were similarly misexpressed in both mutants. In addition, metabolic profiles of mature leaves revealed that several biosynthetic pathways downstream of pyruvate are altered in re and rer3. Double mutant analysis showed that only re rer1 and rer5 rer6 exhibited synergistic phenotypes, indicating functional redundancy. The redundancy between RE and its closest paralog, RER1, was confirmed by overexpressing RER1 in re mutants, which partially suppressed leaf reticulation. Our results show that RER family members can be divided into four functional modules with divergent functions. Moreover, these results provide insights into the origin of the reticulated phenotype, suggesting that the RER proteins functionally interconnect photoperiodic growth, amino acid homeostasis, and reactive oxygen species metabolism during Arabidopsis leaf growth.

Perez-Perez, Jose Manuel; Esteve-Bruna, David; Gonzalez-Bayon, Rebeca; Kangasjarvi, Saijaliisa; Caldana, Camila; Hannah, Matthew A.; Willmitzer, Lothar; Ponce, Maria Rosa; Micol, Jose Luis

2013-01-01

16

Common Single Nucleotide Polymorphisms in Genes Related to Immune Function and Risk of Papillary Thyroid Cancer  

PubMed Central

Accumulating evidence suggests that alterations in immune function may be important in the etiology of papillary thyroid cancer (PTC). To identify genetic markers in immune-related pathways, we evaluated 3,985 tag single nucleotide polymorphisms (SNPs) in 230 candidate gene regions (adhesion-extravasation-migration, arachidonic acid metabolism/eicosanoid signaling, complement and coagulation cascade, cytokine signaling, innate pathogen detection and antimicrobials, leukocyte signaling, TNF/NF-kB pathway or other) in a case-control study of 344 PTC cases and 452 controls. We used logistic regression models to estimate odds ratios (OR) and calculate one degree of freedom P values of linear trend (PSNP-trend) for the association between genotype (common homozygous, heterozygous, variant homozygous) and risk of PTC. To correct for multiple comparisons, we applied the false discovery rate method (FDR). Gene region- and pathway-level associations (PRegion and PPathway) were assessed by combining individual PSNP-trend values using the adaptive rank truncated product method. Two SNPs (rs6115, rs6112) in the SERPINA5 gene were significantly associated with risk of PTC (PSNP-FDR/PSNP-trend?=?0.02/6×10?6 and PSNP-FDR/PSNP-trend?=?0.04/2×10?5, respectively). These associations were independent of a history of autoimmune thyroiditis (OR?=?6.4; 95% confidence interval: 3.0–13.4). At the gene region level, SERPINA5 was suggestively associated with risk of PTC (PRegion-FDR/PRegion?=?0.07/0.0003). Overall, the complement and coagulation cascade pathway was the most significant pathway (PPathway?=?0.02) associated with PTC risk largely due to the strong effect of SERPINA5. Our results require replication but suggest that the SERPINA5 gene, which codes for the protein C inhibitor involved in many biological processes including inflammation, may be a new susceptibility locus for PTC.

Brenner, Alina V.; Neta, Gila; Sturgis, Erich M.; Pfeiffer, Ruth M.; Hutchinson, Amy; Yeager, Meredith; Xu, Li; Zhou, Cindy; Wheeler, William; Tucker, Margaret A.; Chanock, Stephen J.; Sigurdson, Alice J.

2013-01-01

17

Functional effects of congenital myopathy-related mutations in gamma-tropomyosin gene.  

PubMed

Missense mutations in human TPM3 gene encoding ?-tropomyosin expressed in slow muscle type 1 fibers, were associated with three types of congenital myopathies-nemaline myopathy, cap disease and congenital fiber type disproportion. Functional effects of the following substitutions: Leu100Met, Ala156Thr, Arg168His, Arg168Cys, Arg168Gly, Lys169Glu, and Arg245Gly, were examined in biochemical assays using recombinant tropomyosin mutants and native proteins isolated from skeletal muscle. Most, but not all, mutations decreased the affinity of tropomyosin for actin alone and in complex with troponin (±Ca(2+)). All studied tropomyosin mutants reduced Ca-induced activation but had no effect on the inhibition of actomyosin cross-bridges. Ca(2+)-sensitivity of the actomyosin interactions, as well as cooperativity of myosin-induced activation of the thin filament was affected by individual tropomyosin mutants with various degrees. Decreased motility of the reconstructed thin filaments was a result of combined functional defects caused by myopathy-related tropomyosin mutants. We conclude that muscle weakness and structural abnormalities observed in TPM3-related congenital myopathies result from reduced capability of the thin filament to fully activate actin-myosin cross-bridges. PMID:22749829

Robaszkiewicz, Katarzyna; Dudek, El?bieta; Kasprzak, Andrzej A; Moraczewska, Joanna

2012-06-27

18

SARS-CoV Regulates Immune Function-Related Gene Expression in Human Monocytic Cells  

PubMed Central

Abstract Severe acute respiratory syndrome (SARS) is characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis, and monocytes/macrophages are the key players in the pathogenesis of SARS. In this study, we compared the transcriptional profiles of SARS coronavirus (SARS-CoV)-infected monocytic cells against that infected by coronavirus 229E (CoV-229E). Total RNA was extracted from infected DC-SIGN-transfected monocytes (THP-1-DC-SIGN) at 6 and 24?h after infection, and the gene expression was profiled in oligonucleotide-based microarrays. Analysis of immune-related gene expression profiles showed that at 24?h after SARS-CoV infection: (1) IFN-?/?-inducible and cathepsin/proteasome genes were downregulated; (2) hypoxia/hyperoxia-related genes were upregulated; and (3) TLR/TLR-signaling, cytokine/cytokine receptor-related, chemokine/chemokine receptor-related, lysosome-related, MHC/chaperon-related, and fibrosis-related genes were differentially regulated. These results elucidate that SARS-CoV infection regulates immune-related genes in monocytes/macrophages, which may be important to the pathogenesis of SARS.

Hu, Wanchung; Yen, Yu-Ting; Singh, Sher; Kao, Chuan-Liang

2012-01-01

19

Serotonin-Related Gene Polymorphisms and Central Nervous System Serotonin Function  

Microsoft Academic Search

Central nervous system (CNS) serotonergic function affects a wide range of biological and behavioral functions affecting health and disease. Our objective in this study was to determine whether functional polymorphisms of the genes that encode for the serotonin transporter promoter (5HTTLPR) and monoamine oxidase A (MAOA-uVNTR) are associated with CNS serotonin turnover—indexed by cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA)—in

Redford B Williams; Douglas A Marchuk; Kishore M Gadde; John C Barefoot; Katherine Grichnik; Michael J Helms; Cynthia M Kuhn; James G Lewis; Saul M Schanberg; Mark Stafford-Smith; Edward C Suarez; Greg L Clary; Ingrid K Svenson; Ilene C Siegler

2003-01-01

20

Match/X, A gene expression pattern recognition algorithm used to identify genes which may be related to CDC2 function and cell cycle regulation.  

PubMed

Large-scale microarray gene expression studies can provide insight into complex genetic networks and biological pathways. A comprehensive gene expression database was constructed using Affymetrix GeneChip microarrays and RNA isolated from more than 6,400 distinct normal and diseased human tissues. These individual patient samples were grouped into over 700 sample sets based on common tissue and disease morphologies, and each set contained averaged expression data for over 45,000 gene probe sets representing more than 33,000 known human genes. Sample sets were compared to each other in more than 750 normal vs. disease pairwise comparisons. Relative up or downregulation patterns of genes across these pairwise comparisons provided unique expression fingerprints that could be compared and matched to a gene of interest using the Match/X trade mark algorithm. This algorithm uses the kappa statistic to compute correlations between genes and calculate a distance score between a gene of interest and all other genes in the database. Using cdc2 as a query gene, we identified several hundred genes that had similar expression patterns and highly correlated distance scores. Most of these genes were known components of the cell cycle involved in G2/M progression, spindle function or chromosome arrangement. Some of the identified genes had unknown biological functions but may be related to cdc2 mediated mechanism based on their closely correlated distance scores. This algorithm may provide novel insights into unknown gene function based on correlation to expression profiles of known genes and can identify elements of cellular pathways and gene interactions in a high throughput fashion. PMID:15136762

Coberley, Carter; Elashoff, Michael; Mertz, Lawrence

2004-06-02

21

Expression and Functional Characterization of two Pathogenesis-Related Protein 10 Genes from Zea mays  

Technology Transfer Automated Retrieval System (TEKTRAN)

Pathogenesis-related protein 10 (PR10) is one of seventeen PR protein families and plays important roles in plant response to biotic and abiotic stresses. A novel PR10 gene (ZmPR10.1), which shares 89.8% and 85.7% identity to the previous ZmPR10 at the nucleotide and amino acid sequence level, respe...

22

MicroRNA prediction and its function in regulating drought-related genes in cowpea.  

PubMed

Cowpea has indigenous drought-tolerant characteristics, but the molecular mechanisms underlying the drought-tolerance are largely unknown. Drought sensitive and resistant cowpea have different responses regarding to drought stress. We applied homology search to predict miRNAs and their corresponding targets. The newly identified cowpea miRNAs were validated by real-time quantitative PCR in the leaves and roots of cowpea plants under drought treatment. Target gene prediction shows that a set of miRNA target genes are involved in the metabolic pathways regarding the physiological changes that are highly related to drought stress. We analyzed the expression levels of some important genes that participate in the physiological responses to drought stress and found that variations in their expression levels correspond well to the different responses of drought sensitive and resistant cowpea to drought stress. The expression levels of the target genes were negatively correlated to those of miRNAs. The same miRNA in different tissues responds differently to drought stress. Our results indicate that miRNAs play important roles in response to drought stress by regulating the expression levels of drought-related genes in cowpea. PMID:23849110

Shui, Xiao-Rong; Chen, Zhi-Wen; Li, Jian-Xiong

2013-05-13

23

Calcitonin receptor-stimulating peptide: Its evolutionary and functional relationship with calcitonin\\/calcitonin gene-related peptide based on gene structure  

Microsoft Academic Search

This review focuses on the evolutionary and functional relationship of calcitonin receptor-stimulating peptide (CRSP) with calcitonin (CT)\\/calcitonin gene-related peptide (CGRP) in mammals. CRSP shows high sequence identity with CGRP, but distinct biological properties. CRSP genes (CRSPs) have been identified in mammals such as pigs and dogs of the Laurasiatheria, but not in primates and rodents of the Euarchontoglires or in

Takeshi Katafuchi; Hiroshi Yasue; Tsukasa Osaki; Naoto Minamino

2009-01-01

24

The product of Saccharomyces cerevisiae WHIP\\/MGS1 , a gene related to replication factor C genes, interacts functionally with DNA polymerase d  

Microsoft Academic Search

The Saccharomyces cerevisiae gene WHIP\\/MGS1 encodes a protein related to the subunits of Replication Factor C (RFC). We found that the RFC-like motifs in Whip\\/Mgs1 are essential for its function. Furthermore, by screening for synthetic dosage lethality, we have shown that overexpression of MGS1 causes lethality in combination with mutations in genes that encode replication proteins such as DNA polymerase

D. Branzei; M. Seki; F. Onoda; T. Enomoto

2002-01-01

25

A genome-wide survey and functional brain imaging study identify CTNNBL1 as a memory-related gene  

PubMed Central

Unbiased genome-wide screens combined with imaging data on brain function may identify novel molecular pathways related to human cognition. Here we performed a dense genome-wide screen to identify episodic memory-related gene variants. A genomic locus encoding the brain-expressed beta-catenin-like protein 1 (CTNNBL1) was significantly (P=7 × 10?8) associated with verbal memory performance in a cognitively healthy cohort from Switzerland (n=1073) and was replicated in a second cohort from Serbia (n=524; P=0.003). Gene expression studies showed CTNNBL1 genotype-dependent differences in beta-catenin-like protein 1 mRNA levels in the human cortex. Functional magnetic resonance imaging in 322 subjects detected CTNNBL1 genotype-dependent differences in memory-related brain activations. Converging evidence from independent experiments and different methodological approaches suggests a role for CTNNBL1 in human memory.

Papassotiropoulos, A; Stefanova, E; Vogler, C; Gschwind, L; Ackermann, S; Spalek, K; Rasch, B; Heck, A; Aerni, A; Hanser, E; Demougin, P; Huynh, K-D; Luechinger, R; Klarhofer, M; Novakovic, I; Kostic, V; Boesiger, P; Scheffler, K; de Quervain, D J-F

2013-01-01

26

A genome-wide survey and functional brain imaging study identify CTNNBL1 as a memory-related gene.  

PubMed

Unbiased genome-wide screens combined with imaging data on brain function may identify novel molecular pathways related to human cognition. Here we performed a dense genome-wide screen to identify episodic memory-related gene variants. A genomic locus encoding the brain-expressed beta-catenin-like protein 1 (CTNNBL1) was significantly (P=7 × 10(-8)) associated with verbal memory performance in a cognitively healthy cohort from Switzerland (n=1073) and was replicated in a second cohort from Serbia (n=524; P=0.003). Gene expression studies showed CTNNBL1 genotype-dependent differences in beta-catenin-like protein 1 mRNA levels in the human cortex. Functional magnetic resonance imaging in 322 subjects detected CTNNBL1 genotype-dependent differences in memory-related brain activations. Converging evidence from independent experiments and different methodological approaches suggests a role for CTNNBL1 in human memory. PMID:22105620

Papassotiropoulos, A; Stefanova, E; Vogler, C; Gschwind, L; Ackermann, S; Spalek, K; Rasch, B; Heck, A; Aerni, A; Hanser, E; Demougin, P; Huynh, K-D; Luechinger, R; Klarhöfer, M; Novakovic, I; Kostic, V; Boesiger, P; Scheffler, K; de Quervain, D J-F

2011-11-22

27

Discovery of genes related to insecticide resistance in Bactrocera dorsalis by functional genomic analysis of a de novo assembled transcriptome.  

PubMed

Insecticide resistance has recently become a critical concern for control of many insect pest species. Genome sequencing and global quantization of gene expression through analysis of the transcriptome can provide useful information relevant to this challenging problem. The oriental fruit fly, Bactrocera dorsalis, is one of the world's most destructive agricultural pests, and recently it has been used as a target for studies of genetic mechanisms related to insecticide resistance. However, prior to this study, the molecular data available for this species was largely limited to genes identified through homology. To provide a broader pool of gene sequences of potential interest with regard to insecticide resistance, this study uses whole transcriptome analysis developed through de novo assembly of short reads generated by next-generation sequencing (NGS). The transcriptome of B. dorsalis was initially constructed using Illumina's Solexa sequencing technology. Qualified reads were assembled into contigs and potential splicing variants (isotigs). A total of 29,067 isotigs have putative homologues in the non-redundant (nr) protein database from NCBI, and 11,073 of these correspond to distinct D. melanogaster proteins in the RefSeq database. Approximately 5,546 isotigs contain coding sequences that are at least 80% complete and appear to represent B. dorsalis genes. We observed a strong correlation between the completeness of the assembled sequences and the expression intensity of the transcripts. The assembled sequences were also used to identify large numbers of genes potentially belonging to families related to insecticide resistance. A total of 90 P450-, 42 GST-and 37 COE-related genes, representing three major enzyme families involved in insecticide metabolism and resistance, were identified. In addition, 36 isotigs were discovered to contain target site sequences related to four classes of resistance genes. Identified sequence motifs were also analyzed to characterize putative polypeptide translational products and associate them with specific genes and protein functions. PMID:22879883

Hsu, Ju-Chun; Chien, Ting-Ying; Hu, Chia-Cheng; Chen, Mei-Ju May; Wu, Wen-Jer; Feng, Hai-Tung; Haymer, David S; Chen, Chien-Yu

2012-08-07

28

Combination Training in Aging Individuals Modifies Functional Connectivity and Cognition, and Is Potentially Affected by Dopamine-Related Genes  

PubMed Central

Background Aging is a major co-risk factor in many neurodegenerative diseases. Cognitive enrichment positively affects the structural plasticity of the aging brain. In this study, we evaluated effects of a set of structured multimodal activities (Combination Training; CT) on cognitive performances, functional connectivity, and cortical thickness of a group of healthy elderly individuals. CT lasted six months. Methodology Neuropsychological and occupational performances were evaluated before and at the end of the training period. fMRI was used to assess effects of training on resting state network (RSN) functional connectivity using Independent Component Analysis (ICA). Effects on cortical thickness were also studied. Finally, we evaluated whether specific dopamine-related genes can affect the response to training. Principal Findings Results of the study indicate that CT improves cognitive/occupational performances and reorganizes functional connectivity. Intriguingly, individuals responding to CT showed specific dopamine-related genotypes. Indeed, analysis of dopamine-related genes revealed that carriers of DRD3 ser9gly and COMT Val158Met polymorphisms had the greatest benefits from exposure to CT. Conclusions and Significance Overall, our findings support the idea that exposure to a set of structured multimodal activities can be an effective strategy to counteract aging-related cognitive decline and also indicate that significant capability of functional and structural changes are maintained in the elderly.

Pieramico, Valentina; Esposito, Roberto; Sensi, Francesca; Cilli, Franco; Mantini, Dante; Mattei, Peter A.; Frazzini, Valerio; Ciavardelli, Domenico; Gatta, Valentina; Ferretti, Antonio; Romani, Gian Luca; Sensi, Stefano L.

2012-01-01

29

Expression Profiles and Functional Analyses of Wnt-Related Genes in Human Joint Disorders  

Microsoft Academic Search

Rheumatoid arthritis (RA) and osteoarthritis (OA) are joint disorders that cause major public health prob- lems. Previous studies of the etiology of RA and OA have implicated Wnt genes, although the exact nature of their involvement remains unclear. To further clarify the relationship between RA, OA, and the Wnt gene family, gene expression analyses were per- formed on articular cartilage,

Yukio Nakamura; Masashi Nawata; Shigeyuki Wakitani

2005-01-01

30

Effects of forced running exercise on cognitive function and its relation to zinc homeostasis-related gene expression in rat hippocampus.  

PubMed

Voluntary exercise has been implicated to be beneficial for overall health and cognitive function in both clinical and experimental studies, but little is presently known about forced physical exercise on cognition and underlying molecular mechanism. We have used real-time RT-PCR to analyze gene expression in hippocampus, in the presence and absence of physical exercise, during spatial learning of rats in the Morris water maze. Our results show distinct zinc homeostasis-related gene expression profiles associated with learning and memory. Rats with physical exercise (EXP) showed a significant up-regulation of mRNA expression of zinc transporter-2 (ZnT-2), ZnT-4, ZnT-5, ZnT-6, and ZnT-7, metallothionein-1 (MT-1)-MT-3, divalent cation transporter-1, and Zrt-Irt-like proteins-7 in hippocampus when compared with control rats. In addition, spatial learning ability was improved in EXP rats compared with that in control group. This study provides the first comparative view of zinc homeostasis-related gene expression in hippocampus following forced physical exercise. These results suggested that forced physical exercise may provide a simple means to maintain brain function and promote learning capacity. Results of this study also suggest that exercise mobilizes zinc homeostasis-related gene expression profiles that would be predicted to benefit brain plasticity processes. PMID:20703826

Ni, Hong; Li, Chao; Feng, Xing; Cen, Jian-Nong

2010-08-12

31

Green tea polyphenols function as prooxidants to inhibit Pseudomonas aeruginosa and induce the expression of oxidative stress-related genes.  

PubMed

Green tea polyphenols (GTP) are widely believed to function as antioxidants and antimicrobial agents. Here we observed that GTP and epigallocatechin gallate, the most abundant catechin in GTP, could also function as prooxidants and produce hydrogen peroxide (H2O2) to inhibit the growth of Pseudomonas aeruginosa. pH value of the medium was the key factor that affected prooxidant versus antioxidant property of GTP. Under weakly acidic conditions (pH 5.5-6.5), GTP showed antioxidant activity by eliminating H2O2; whereas, under neutral and weakly alkaline conditions (pH 7.0-8.0), GTP showed prooxidant activity and inhibited the growth of P. aeruginosa. Furthermore, we studied the effects of GTP on gene expression profiles of a few oxidative stress-related genes by quantitative real-time PCR analysis. After 10 min to 1 h of exposure under weakly alkaline condition, GTP significantly up-regulated expression levels of katB, sodM, ohr, lexA, and recN gene. These findings highlight that the pH-dependent H2O2 production by GTP contributes to the antibacterial activity and can induce oxidative stress-related responses in P. aeruginosa. PMID:23054687

Liu, Xiaoxiang; Li, Jianrong; Wang, Yanbo; Li, Tingting; Zhao, Jin; Zhang, Chaohua

2012-10-10

32

Functional mutation in the promoter region of thrombomodulin gene in relation to carotid atherosclerosis  

Microsoft Academic Search

Thrombomodulin is an important endothelial anticoagulant protein that decreases thrombin activity and activates protein C. Our recent study has shown that the G-33A promoter mutation of thrombomodulin gene is associated with coronary artery disease. This study was conducted to determine whether the G-33A mutation in the promoter region of thrombomodulin gene is a genetic risk factor for ischemic stroke or

Yi-Heng Li; Chih-Hung Chen; Poh-Shiow Yeh; Huey-Juan Lin; Bi-Ing Chang; Jia-Chung Lin; How-Ran Guo; Hua-Lin Wu; Guey-Yueh Shi; Ming-Liang Lai; Jyh-Hong Chen

2001-01-01

33

Structure and Expression Analyses of SVA Elements in Relation to Functional Genes  

PubMed Central

SINE-VNTR-Alu (SVA) elements are present in hominoid primates and are divided into 6 subfamilies (SVA-A to SVA-F) and active in the human population. Using a bioinformatic tool, 22 SVA element-associated genes are identified in the human genome. In an analysis of genomic structure, SVA elements are detected in the 5' untranslated region (UTR) of HGSNAT (SVA-B), MRGPRX3 (SVA-D), HYAL1 (SVA-F), TCHH (SVA-F), and ATXN2L (SVA-F) genes, while some elements are observed in the 3'UTR of SPICE1 (SVA-B), TDRKH (SVA-C), GOSR1 (SVA-D), BBS5 (SVA-D), NEK5 (SVA-D), ABHD2 (SVA-F), C1QTNF7 (SVA-F), ORC6L (SVA-F), TMEM69 (SVA-F), and CCDC137 (SVA-F) genes. They could contribute to exon extension or supplying poly A signals. LEPR (SVA-C), ALOX5 (SVA-D), PDS5B (SVA-D), and ABCA10 (SVA-F) genes also showed alternative transcripts by SVA exonization events. Dominant expression of HYAL1_SVA appeared in lung tissues, while HYAL1_noSVA showed ubiquitous expression in various human tissues. Expression of both transcripts (TDRKH_SVA and TDRKH_noSVA) of the TDRKH gene appeared to be ubiquitous. Taken together, these data suggest that SVA elements cause transcript isoforms that contribute to modulation of gene regulation in various human tissues.

Kwon, Yun-Jeong; Choi, Yuri; Eo, Jungwoo; Noh, Yu-Na; Gim, Jeong-An; Jung, Yi-Deun; Lee, Ja-Rang

2013-01-01

34

Estrogen-related receptor {alpha} is essential for the expression of antioxidant protection genes and mitochondrial function  

SciTech Connect

Estrogen-related receptor {alpha} (ERR{alpha}) is an important mediator of mitochondrial biogenesis and function. To investigate the transcriptional network controlling these phenomena, we investigated mitochondrial gene expression in embryonic fibroblasts isolated from ERR{alpha} null mice. Peroxisome proliferator-activated receptor {gamma} coactivator-1{alpha} (PGC-1{alpha}) stimulated mitochondrial gene expression program in control cells, but not in the ERR{alpha} null cells. Interestingly, the induction of levels of mitochondrial oxidative stress protection genes in response to increased PGC-1{alpha} levels was dependent on ERR{alpha}. Furthermore, we found that the PGC-1{alpha}-mediated induction of estrogen-related receptor {gamma} and nuclear respiratory factor 2 (NRF-2), was dependent on the presence of ERR{alpha}. Basal levels of NRF-2 were decreased in the absence of ERR{alpha}. The absence of ERR{alpha} resulted in a decrease in citrate synthase enzyme activity in response to PGC-1{alpha} overexpression. Our results indicate an essential role for ERR{alpha} as a key regulator of oxidative metabolism.

Rangwala, Shamina M. [Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States)]. E-mail: shamina.rangwala@novartis.com; Li, Xiaoyan [Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States); Lindsley, Loren [Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States); Wang, Xiaomei [Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States); Shaughnessy, Stacey [Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States); Daniels, Thomas G. [Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States); Szustakowski, Joseph [Genome and Proteome Sciences, Novartis Institutes of BioMedical Research Institutes, 500 Technology Square, Cambridge, MA 02139 (United States); Nirmala, N.R. [Genome and Proteome Sciences, Novartis Institutes of BioMedical Research Institutes, 500 Technology Square, Cambridge, MA 02139 (United States); Wu, Zhidan [Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States); Stevenson, Susan C. [Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States)

2007-05-25

35

Ameliorated stress related proteins are associated with improved cardiac function by sarcoplasmic reticulum calcium ATPase gene transfer in heart failure  

PubMed Central

Background Previous studies showed that overexpression of sarco-endoplasmic reticulum calcium ATPase (SERCA2a) in a variety of heart failure (HF) models was associated with greatly enhanced cardiac performance. However, it still undefined the effect of SERCA2a overexpression on the systemic inflammatory response and neuro-hormonal factors. Methods A rapid right ventricular pacing model of experimental HF was used in beagles. Then the animals underwent recombinant adeno-associated virus 1 (rAAV1) mediated gene transfection by direct intra-myocardium injection. HF animals were randomized to receive the SERCA2a gene, enhanced green fluorescent protein (control) gene, or equivalent phosphate buffered saline. Thirty days after gene delivery, the cardiac function was evaluated by echocardiographic testing. The protein level of SERCA2a was measured by western blotting. The proteomic analysis of left ventricular (LV) sample was determined using two-dimensional (2-D) gel electrophoresis and MALDI-TOF-MS. The serum levels of the systemic inflammatory and neuro-hormonal factors were assayed using radioimmunoassay kits. Results The cardiac function improved after SERCA- 2a gene transfer due to the significantly increased SERCA2a protein level. Beagles treated with SERCA2a had significantly decreased serum levels of the inflammatory markers (interleukin-6 and tumor necrosis factor-?) and neuro-hormonal factors (brain natriuretic peptide, endothelin-1 and angiotensin II) compared with HF animals. The myocardial proteomic analysis showed that haptoglobin heavy chain, heat shock protein (alpha-crystallin-related, B6) were down-regulated, and galectin-1 was up-regulated in SERCA2a group compared with HF group, companied by up-regulated contractile proteins and NADH dehydrogenase. Conclusions These findings demonstrate that regional intramyocardial injections of rAAV1-SERCA2a vectors may improve global LV function, correlating with reverse activation of the systemic inflammatory, excessive neuroendocrine factors and the stress-associated myocardial proteins, suggesting that the beneficial effects of SERCA2a gene transfer may involve the attenuation of stress-associated reaction.

Fu, Zhi-Qing; Li, Xiao-Ying; Lu, Xiao-Chun; Mi, Ya-Fei; Liu, Tao; Ye, Wei-Hua

2012-01-01

36

Monoamine related functional gene variants and relationships to monoamine metabolite concentrations in CSF of healthy volunteers  

PubMed Central

Background Concentrations of monoamine metabolites in human cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. CSF monoamine metabolite concentrations are partly determined by genetic influences. Methods We investigated possible relationships between DNA polymorphisms in the serotonin 2C receptor (HTR2C), the serotonin 3A receptor (HTR3A), the dopamine D4 receptor (DRD4), and the dopamine ?-hydroxylase (DBH) genes and CSF concentrations of 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 90). Results The HTR3A 178 C/T variant was associated with 5-HIAA levels (p = 0.02). The DBH-1021 heterozygote genotype was associated with 5-HIAA (p = 0.0005) and HVA (p = 0.009) concentrations. Neither the HTR2C Cys23Ser variant, nor the DRD4 -521 C/T variant were significantly associated with any of the monoamine metabolites. Conclusions The present results suggest that the HTR3A and DBH genes may participate in the regulation of dopamine and serotonin turnover rates in the central nervous system.

Jonsson, Erik G; Bah, Jessica; Melke, Jonas; Abou Jamra, Rami; Schumacher, Johannes; Westberg, Lars; Ivo, Roland; Cichon, Sven; Propping, Peter; Nothen, Markus M; Eriksson, Elias; Sedvall, Goran C

2004-01-01

37

Brassica GLABRA2 genes: analysis of function related to seed oil content and development of functional markers  

Microsoft Academic Search

Regulation of seed oil accumulation in oilseed rape (Brassica napus) has important economic significance. However, few genes have been characterized that affect final seed oil content. Through\\u000a a mutant identification, the class IV homeodomain-ZIP transcription factor GLABRA2 (GL2) has been found to regulate seed oil\\u000a accumulation in Arabidopsis, in addition to its role in trichome development. In this study, we

Guohua Chai; Zetao Bai; Fang Wei; Graham J. King; Chenggang Wang; Lei Shi; Caihua Dong; Hong Chen; Shengyi Liu

2010-01-01

38

Expanding the Landscape of Chromatin Modification (CM)Related Functional Domains and Genes in Human  

Microsoft Academic Search

Chromatin modification (CM) plays a key role in regulating transcription, DNA replication, repair and recombination. However, our knowledge of these processes in humans remains very limited. Here we use computational approaches to study proteins and functional domains involved in CM in humans. We analyze the abundance and the pair-wise domain-domain co-occurrences of 25 well-documented CM domains in 5 model organisms:

Shuye Pu; Andrei L. Turinsky; James Vlasblom; Tuan On; Xuejian Xiong; Andrew Emili; Zhaolei Zhang; Jack Greenblatt; John Parkinson; Shoshana J. Wodak; Tim J. Hubbard

2010-01-01

39

Delineating the structural, functional and evolutionary relationships of sucrose phosphate synthase gene family II in wheat and related grasses  

PubMed Central

Background Sucrose phosphate synthase (SPS) is an important component of the plant sucrose biosynthesis pathway. In the monocotyledonous Poaceae, five SPS genes have been identified. Here we present a detailed analysis of the wheat SPSII family in wheat. A set of homoeologue-specific primers was developed in order to permit both the detection of sequence variation, and the dissection of the individual contribution of each homoeologue to the global expression of SPSII. Results The expression in bread wheat over the course of development of various sucrose biosynthesis genes monitored on an Affymetrix array showed that the SPS genes were regulated over time and space. SPSII homoeologue-specific assays were used to show that the three homoeologues contributed differentially to the global expression of SPSII. Genetic mapping placed the set of homoeoloci on the short arms of the homoeologous group 3 chromosomes. A resequencing of the A and B genome copies allowed the detection of four haplotypes at each locus. The 3B copy includes an unspliced intron. A comparison of the sequences of the wheat SPSII orthologues present in the diploid progenitors einkorn, goatgrass and Triticum speltoides, as well as in the more distantly related species barley, rice, sorghum and purple false brome demonstrated that intronic sequence was less well conserved than exonic. Comparative sequence and phylogenetic analysis of SPSII gene showed that false purple brome was more similar to Triticeae than to rice. Wheat - rice synteny was found to be perturbed at the SPS region. Conclusion The homoeologue-specific assays will be suitable to derive associations between SPS functionality and key phenotypic traits. The amplicon sequences derived from the homoeologue-specific primers are informative regarding the evolution of SPSII in a polyploid context.

2010-01-01

40

Potentially functional genetic variants in microRNA processing genes and risk of HBV-related hepatocellular carcinoma.  

PubMed

Genetic variations in miRNA processing genes may affect the biogenesis of miRNA, hence risk of HBV infection and hepatocellular carcinoma (HCC) development. In the present study, we hypothesized that potentially functional polymorphisms in 3'-untranslated region (UTR) of miRNA processing genes might contribute to susceptibility of HBV infection and HCC development. To test the hypothesis, we genotyped three selected SNPs (rs1057035 in DICER1, rs3803012 in RAN, and rs10773771 in PIWIL1) in a case-control study of 1300 HBV-positive HCC cancer cases, 1344 HBV persistent carriers, and 1344 HBV natural clearance subjects in Chinese. We observed that DICER1 rs1057035 CT/CC variant genotypes were associated with a significant decreased risk of HCC (adjusted OR?=?0.79, 95% CI?=?0.64-0.96) compared with wild-type TT and RAN rs3803012 AG/GG variant genotypes increased the risk of HBV persistent infection compared with AA genotype (adjusted OR?=?1.35, 95% CI?=?1.03-1.77). However, PIWIL1 rs10773771 CT/CC variant genotypes were associated with an approaching decreased risk of HCC (adjusted OR?=?0.86, 95% CI?=?0.73-1.01) and similar with RAN rs3803012 AG/GG (adjusted OR?=?0.80, 95% CI?=?0.61-1.06). Furthermore, reporter gene assays indicated that the three SNPs (rs1057035, rs3803012, and rs10773771) might change the binding ability of miRNAs to the 3'UTR of the three genes (DICER1, RAN, and PIWIL1), respectively. These findings indicated that DICER1 rs1057035, RAN rs3803012, and PIWIL1 rs10773771 might contribute to the risk of HBV-related HCC. © 2013 Wiley Periodicals, Inc. PMID:23868705

Liu, Li; An, Jiaze; Liu, Jibin; Wen, Juan; Zhai, Xiangjun; Liu, Yao; Pan, Shandong; Jiang, Jie; Wen, Yang; Liu, Zheng; Zhang, Yixin; Chen, Jianguo; Xing, Jinliang; Ji, Guozhong; Shen, Hongbing; Hu, Zhibin; Fan, Zhining

2013-07-19

41

Functional analysis of pig myostatin gene promoter with some adipogenesis- and myogenesis-related factors.  

PubMed

Myostatin (MSTN) is primarily expressed in muscle and plays an important role in muscle and fat development in pigs. However, there is little information about the regulation of pig MSTN. In order to elucidate whether pig MSTN could be regulated by muscle- and fat-related factors, the porcine MSTN promoter was amplified and cloned into pGL3-basic vector, and transfected into cells to analyze the transcriptional activity of promoter with muscle- and fat-related factors through dual-luciferase reporter assays. 5'-deletion expression showed that there was a negative-regulatory region located between nucleotides -1519 and -1236 bp, and there were some positive-regulatory regions located between -1236 and -568 bp. The longest fragment (1.7 kb) was cotransfected with muscle-related transcription factor myogenic differentiation 1 (MyoD), resulting in promoter transcriptional activity upregulation. The fragment was treated by the adipogenic agents (DIM) including dexamethasone, insulin, and isobutyl-1-methylxanthine (IBMX). We found that MSTN promoter transcriptional activity can be regulated by IBMX, but not by DIM. CCAAT/enhancer binding protein (C/EBP) ? and C/EBP?, two proteins which are induced by DIM during adipogenesis were cotransfected with the 1.7-kb fragment, respectively, resulting in promoter transcriptional activity downregulation. Treating the fragment with rosiglitazone which induce the expression of peroxisome proliferator-activated receptor ? (PPAR?), resulting in promoter transcriptional activity upregulation. Cotransfection experiments confirmed this result. Taken together, we showed that porcine MSTN could be upregulated by IBMX, MyoD, and PPAR? but downregulated by C/EBP? and C/EBP?. PMID:22160830

Deng, Bing; Wen, Jianghui; Ding, Yi; Gao, Qishuang; Huang, Haijun; Ran, Zhiping; Qian, Yunguo; Peng, Jian; Jiang, Siwen

2011-12-11

42

Effect of aging on insulin secretory function and expression of beta cell function-related genes of islets  

Microsoft Academic Search

Recently, the glucose-stimulated insulin release of isolated human islets has been shown to deteriorate progressively with advancing donor age. This decline in beta cell function with aging may contribute to the increasing development of IGT and type 2 diabetes and also to the progressive nature of the disease. This study was to see whether there is any change in expression

Sung-Hee Ihm; Hong Ju Moon; Jun Goo Kang; Cheol Young Park; Ki Won Oh; In Kyung Jeong; Yang-Seok Oh; Sung Woo Park

2007-01-01

43

Loss-of-Function of Constitutive Expresser of Pathogenesis Related Genes5 Affects Potassium Homeostasis in Arabidopsis thaliana  

PubMed Central

Here, we demonstrate that the reduction in leaf K+ observed in a mutant previously identified in an ionomic screen of fast neutron mutagenized Arabidopsis thaliana is caused by a loss-of-function allele of CPR5, which we name cpr5-3. This observation establishes low leaf K+ as a new phenotype for loss-of-function alleles of CPR5. We investigate the factors affecting this low leaf K+ in cpr5 using double mutants defective in salicylic acid (SA) and jasmonic acid (JA) signalling, and by gene expression analysis of various channels and transporters. Reciprocal grafting between cpr5 and Col-0 was used to determine the relative importance of the shoot and root in causing the low leaf K+ phenotype of cpr5. Our data show that loss-of-function of CPR5 in shoots primarily determines the low leaf K+ phenotype of cpr5, though the roots also contribute to a lesser degree. The low leaf K+ phenotype of cpr5 is independent of the elevated SA and JA known to occur in cpr5. In cpr5 expression of genes encoding various Cyclic Nucleotide Gated Channels (CNGCs) are uniquely elevated in leaves. Further, expression of HAK5, encoding the high affinity K+ uptake transporter, is reduced in roots of cpr5 grown with high or low K+ supply. We suggest a model in which low leaf K+ in cpr5 is driven primarily by enhanced shoot-to-root K+ export caused by a constitutive activation of the expression of various CNGCs. This activation may enhance K+ efflux, either indirectly via enhanced cytosolic Ca2+ and/or directly by increased K+ transport activity. Enhanced shoot-to-root K+ export may also cause the reduced expression of HAK5 observed in roots of cpr5, leading to a reduction in uptake of K+. All ionomic data presented is publically available at www.ionomicshub.org.

Borghi, Monica; Rus, Ana; Salt, David E.

2011-01-01

44

Functional Candidate Genes in Age-Related Macular Degeneration: Significant Association with VEGF, VLDLR, and LRP6  

Microsoft Academic Search

PURPOSE. Age-related macular degeneration (AMD) is a retinal degenerative disease that is the leading cause of blindness worldwide for individuals over the age of 60. Although the etiology of AMD remains largely unknown, numerous studies have suggested that both genes and environmental risk factors significantly influence the risk of developing AMD. Identifica- tion of the underlying genes has been difficult,

Jonathan L. Haines; Nathalie Schnetz-Boutaud; Silke Schmidt; William K. Scott; Anita Agarwal; Eric A. Postel; Lana Olson; Shannon J. Kenealy; Michael Hauser; John R. Gilbert; Margaret A. Pericak-Vance

2006-01-01

45

Parallel re-modeling of EF-1? function: divergent EF-1? genes co-occur with EFL genes in diverse distantly related eukaryotes  

PubMed Central

Background Elongation factor-1? (EF-1?) and elongation factor-like (EFL) proteins are functionally homologous to one another, and are core components of the eukaryotic translation machinery. The patchy distribution of the two elongation factor types across global eukaryotic phylogeny is suggestive of a ‘differential loss’ hypothesis that assumes that EF-1? and EFL were present in the most recent common ancestor of eukaryotes followed by independent differential losses of one of the two factors in the descendant lineages. To date, however, just one diatom and one fungus have been found to have both EF-1? and EFL (dual-EF-containing species). Results In this study, we characterized 35 new EF-1?/EFL sequences from phylogenetically diverse eukaryotes. In so doing we identified 11 previously unreported dual-EF-containing species from diverse eukaryote groups including the Stramenopiles, Apusomonadida, Goniomonadida, and Fungi. Phylogenetic analyses suggested vertical inheritance of both genes in each of the dual-EF lineages. In the dual-EF-containing species we identified, the EF-1? genes appeared to be highly divergent in sequence and suppressed at the transcriptional level compared to the co-occurring EFL genes. Conclusions According to the known EF-1?/EFL distribution, the differential loss process should have occurred independently in diverse eukaryotic lineages, and more dual-EF-containing species remain unidentified. We predict that dual-EF-containing species retain the divergent EF-1? homologues only for a sub-set of the original functions. As the dual-EF-containing species are distantly related to each other, we propose that independent re-modelling of EF-1? function took place in multiple branches in the tree of eukaryotes.

2013-01-01

46

Determination of the Relative Importance of Gene Function or Taxonomic Grouping to Codon Usage Bias Using Cluster Analysis and SVMs  

Microsoft Academic Search

The codon usage patterns of 2,552 major histocompatibility complex (MHC) sequences from 33 primate species, and the consequent subsets of sequences obtained by removing species with most abundant sequences was observed. The correlation between function and species with regards to MHC codon usage patterns was analyzed using cluster analysis and support vector machines (SVMs). The results show that gene function

Jianmin Ma; Minh Ngoc Nguyen; Gary B. Fogel; Jagath C. Rajapakse

2006-01-01

47

EPConDB: a web resource for gene expression related to pancreatic development, beta-cell function and diabetes.  

PubMed

EPConDB (http://www.cbil.upenn.edu/EPConDB) is a public web site that supports research in diabetes, pancreatic development and beta-cell function by providing information about genes expressed in cells of the pancreas. EPConDB displays expression profiles for individual genes and information about transcripts, promoter elements and transcription factor binding sites. Gene expression results are obtained from studies examining tissue expression, pancreatic development and growth, differentiation of insulin-producing cells, islet or beta-cell injury, and genetic models of impaired beta-cell function. The expression datasets are derived using different microarray platforms, including the BCBC PancChips and Affymetrix gene expression arrays. Other datasets include semi-quantitative RT-PCR and MPSS expression studies. For selected microarray studies, lists of differentially expressed genes, derived from PaGE analysis, are displayed on the site. EPConDB provides database queries and tools to examine the relationship between a gene, its transcriptional regulation, protein function and expression in pancreatic tissues. PMID:17071715

Mazzarelli, Joan M; Brestelli, John; Gorski, Regina K; Liu, Junmin; Manduchi, Elisabetta; Pinney, Deborah F; Schug, Jonathan; White, Peter; Kaestner, Klaus H; Stoeckert, Christian J

2006-10-27

48

Functional analysis of four processing products from multiple precursors encoded by a lebocin-related gene from Manduca sexta.  

PubMed

Antimicrobial peptides (AMPs) are a crucial component of the natural immune system in insects. Five types of AMPs have been identified in the tobacco hornworm Manduca sexta, including attacin, cecropin, moricin, gloverin, and lebocin. Here we report the isolation of lebocin-related cDNA clones and antibacterial activity of their processed protein products. The 17 cDNA sequences are composed of a constant 5' end and a variable 3' region containing 3-16 copies of an 81-nucleotide repeat. The sequence of the corresponding gene isolated from a M. sexta genomic library and Southern blotting results indicated that the gene lacks introns and exists as a single copy in the genome. The genomic sequence contained 13 complete and one partial copy of the 81-nucleotide repeat. Northern blot analysis revealed multiple transcripts with major size differences. The mRNA level of M. sexta lebocin increased substantially in fat body after larvae had been injected with bacteria. The RXXR motifs in the protein sequences led us to postulate that the precursors are processed by an intracellular convertase to form four bioactive peptides. To test this hypothesis, we chemically synthesized the peptides and examined their antibacterial activity. Peptide 1 killed Gram-positive and Gram-negative bacteria. Peptide 2, similar in sequence to a Galleria mellonella AMP, did not affect the bacterial growth. Peptide 3 was inactive but peptide 3 with an extra Arg at the carboxyl terminus was active against Escherichia coli at a high minimum inhibitory concentration. Peptide 4, encoded by the 81-bp repeat, was inactive in the antibacterial tests. The hypothesis that posttranslational processing of the precursor proteins produces multiple bioactive peptides for defense purposes was validated by identification of peptides 1, 2, and 3 from larval hemolymph via liquid chromatography and tandem mass spectrometry. Comparison with the orthologs from other lepidopteran insects indicates that the same mechanism may be used to generate several functional products from a single precursor. PMID:20096726

Rayaprolu, Subrahmanyam; Wang, Yang; Kanost, Michael R; Hartson, Steven; Jiang, Haobo

2010-01-28

49

Functional analysis of four processing products from multiple precursors encoded by a lebocin-related gene from Manduca sexta  

PubMed Central

Antimicrobial peptides (AMPs) are a crucial component of the natural immune system in insects. Five types of AMPs have been identified in the tobacco hornworm Manduca sexta, including attacin, cecropin, moricin, gloverin, and lebocin. Here we report the isolation of lebocin-related cDNA clones and antibacterial activity of their processed protein products. The seventeen cDNA sequences are composed of a constant 5? end and a variable 3? region containing 3?16 copies of an 81-nucleotide repeat. The sequence of the corresponding gene isolated from a M. sexta genomic library and Southern blotting results indicated that the gene lacks introns and exists as a single copy in the genome. The genomic sequence contained 13 complete and one partial copy of the 81-nucleotide repeat. Northern blot analysis revealed multiple transcripts with major size differences. The mRNA level of M. sexta lebocin increased substantially in fat body after larvae had been injected with bacteria. The RXXR motifs in the protein sequences led us to postulate that the precursors are processed by an intracellular convertase to form four bioactive peptides. To test this hypothesis, we chemically synthesized the peptides and examined their antibacterial activity. Peptide 1 killed Gram-positive and Gram-negative bacteria. Peptide 2, similar in sequence to a Galleria mellonella AMP, did not affect the bacterial growth. Peptide 3 was inactive but peptide 3 with an extra Arg at the carboxyl terminus was active against E. coli at a high minimum inhibitory concentration. Peptide 4, encoded by the 81-bp repeat, was inactive in the antibacterial tests. The hypothesis that posttranslational processing of the precursor proteins produces multiple bioactive peptides for defense purposes was validated by identification of peptides 1, 2, and 3 from larval hemolymph via liquid chromatography and tandem mass spectrometry. Comparison with the orthologs from other lepidopteran insects indicates that the same mechanism may be used to generate several functional products from a single precursor.

Rayaprolu, Subrahmanyam; Wang, Yang; Kanost, Michael R.; Hartson, Steven; Jiang, Haobo

2010-01-01

50

Experiments in text-based mining and analysis of biological information from MEDLINE on functionally-related genes  

Microsoft Academic Search

Technological advancements such as microarrays have enabled biologists to generate unprecedented quantities of data about biological entities. This has lead to the development of a large number of algorithms for processing and analysis of biological data. Challenges however remain; for instance, genes that function cooperatively need not have similar expression patterns. This suggests the use of non-numerical sources of information

Naureen Moon; Rahul Singh

2005-01-01

51

Characterization of the Mas-related gene family: structural and functional conservation of human and rhesus MrgX receptors.  

PubMed

Recently, a large family of G-protein-coupled receptors called Mas-related genes (Mrgs), which is selectively expressed in small-diameter sensory neurons of dorsal root ganglia, was described. A subgroup of human Mrg receptors (MrgX1-X4) is not found in rodents and this has hampered efforts to define the physiological roles of these receptors. MrgX receptors were cloned from rhesus monkey and functionally characterized alongside their human orthologs. Most of the human and rhesus MrgX receptors displayed high constitutive activity in a cellular proliferation assay. Proliferative responses mediated by human or rhesus MrgX1, or rhesus MrgX2 were partially blocked by pertussis toxin (PTX). Proliferative responses mediated by rhesus MrgX3 and both human and rhesus MrgX4 were PTX insensitive. These results indicate that human and rhesus MrgX1 and MrgX2 receptors activate both Gq- and Gi-regulated pathways, while MrgX3 and MrgX4 receptors primarily stimulate Gq-regulated pathways. Peptides known to activate human MrgX1 and MrgX2 receptors activated the corresponding rhesus receptors in cellular proliferation assays, Ca(2+)-mobilization assays, and GTP-gammaS-binding assays. Cortistatin-14 was selective for human and rhesus MrgX2 receptors over human and rhesus MrgX1 receptors. BAM22 and related peptides strongly activated human MrgX1 receptors, but weakly activated rhesus MrgX1, human MrgX2, and rhesus MrgX2 receptors. These data suggest that the rhesus monkey may be a suitable animal model for exploring the physiological roles of the MrgX receptors. PMID:16284629

Burstein, Ethan S; Ott, Thomas R; Feddock, Michele; Ma, Jian-Nong; Fuhs, Steve; Wong, Steven; Schiffer, Hans H; Brann, Mark R; Nash, Norman R

2006-01-01

52

Characterization of the Mas-related gene family: structural and functional conservation of human and rhesus MrgX receptors  

PubMed Central

Recently, a large family of G-protein-coupled receptors called Mas-related genes (Mrgs), which is selectively expressed in small-diameter sensory neurons of dorsal root ganglia, was described. A subgroup of human Mrg receptors (MrgX1–X4) is not found in rodents and this has hampered efforts to define the physiological roles of these receptors. MrgX receptors were cloned from rhesus monkey and functionally characterized alongside their human orthologs. Most of the human and rhesus MrgX receptors displayed high constitutive activity in a cellular proliferation assay. Proliferative responses mediated by human or rhesus MrgX1, or rhesus MrgX2 were partially blocked by pertussis toxin (PTX). Proliferative responses mediated by rhesus MrgX3 and both human and rhesus MrgX4 were PTX insensitive. These results indicate that human and rhesus MrgX1 and MrgX2 receptors activate both Gq- and Gi-regulated pathways, while MrgX3 and MrgX4 receptors primarily stimulate Gq-regulated pathways. Peptides known to activate human MrgX1 and MrgX2 receptors activated the corresponding rhesus receptors in cellular proliferation assays, Ca2+-mobilization assays, and GTP-?S-binding assays. Cortistatin-14 was selective for human and rhesus MrgX2 receptors over human and rhesus MrgX1 receptors. BAM22 and related peptides strongly activated human MrgX1 receptors, but weakly activated rhesus MrgX1, human MrgX2, and rhesus MrgX2 receptors. These data suggest that the rhesus monkey may be a suitable animal model for exploring the physiological roles of the MrgX receptors.

Burstein, Ethan S; Ott, Thomas R; Feddock, Michele; Ma, Jian-Nong; Fuhs, Steve; Wong, Steven; Schiffer, Hans H; Brann, Mark R; Nash, Norman R

2005-01-01

53

Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function.  

PubMed

In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10(-9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10(-4)-2.2 × 10(-7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general. PMID:22962313

Chasman, Daniel I; Fuchsberger, Christian; Pattaro, Cristian; Teumer, Alexander; Böger, Carsten A; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; O'Seaghdha, Conall M; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D; Gierman, Hinco J; Feitosa, Mary F; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Lambert, Jean-Charles; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tőnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Coassin, Stefan; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; de Andrade, Mariza; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Meisinger, Christa; Gieger, Christian; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S; van Duijn, Cornelia M; Borecki, Ingrid B; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Parsa, Afshin; Bochud, Murielle; Heid, Iris M; Kao, W H Linda; Fox, Caroline S; Köttgen, Anna

2012-09-08

54

Gene Expression Changes Related to Endocrine Function and Decline in Reproduction in Fathead Minnow (Pimephales promelas) after Dietary Methylmercury Exposure  

PubMed Central

Background Methylmercury (MeHg) is a known neurotoxic agent, but the mechanisms by which MeHg may act on reproductive pathways are relatively unknown. Several studies have indicated potential changes in hormone levels as well as declines in vertebrates with increasing dietary MeHg exposure. Objectives The purpose of this study was to identify alterations in gene expression associated with MeHg exposure, specifically those associated with previously observed changes in reproduction and reproductive biomarkers. Fathead minnows, Pimephales promelas, were fed one of three diets that were similar to documented concentrations of MeHg in the diets of wild invertivorous and piscivorous fish. We used a commercial macroarray in conjunction with quantitative polymerase chain reaction to examine gene expression in fish in relation to exposure to these environmentally relevant doses of MeHg. Results Expression of genes commonly associated with endocrine disruption was altered with Hg exposure. Specifically, we observed a marked up-regulation in vitellogenin mRNA in individual Hg-exposed males and a significant decline in vitellogenin gene expression in female fish with increasing Hg concentrations. Other genes identified by the macroarray experiment included those associated with egg fertilization and development, sugar metabolism, apoptosis, and electron transport. We also observed differences in expression patterns between male and female fish not related to genes specifically associated with reproduction, indicating a potential physiological difference in the reaction of males and females to MeHg. Conclusion Gene expression data may provide insight into the mechanisms by which MeHg affects reproduction in fish and indicate how MeHg differs in its effect from other heavy metals and endocrine-disrupting compounds.

Klaper, Rebecca; Rees, Christopher B.; Drevnick, Paul; Weber, Daniel; Sandheinrich, Mark; Carvan, Michael J.

2006-01-01

55

Gene expression analysis distinguishes tissue-specific and gender-related functions among adult Ascaris suum tissues.  

PubMed

Over a billion people are infected by Ascaris spp. intestinal parasites. To clarify functional differences among tissues of adult A. suum, we compared gene expression by various tissues of these worms by expression microarray methods. The A. suum genome was sequenced and assembled to allow generation of microarray elements. Expression of over 40,000 60-mer elements was investigated in a variety of tissues from both male and female adult worms. Nearly 50 percent of the elements for which signal was detected exhibited differential expression among different tissues. The unique profile of transcripts identified for each tissue clarified functional distinctions among tissues, such as chitin binding in the ovary and peptidase activity in the intestines. Interestingly, hundreds of gender-specific elements were characterized in multiple non-reproductive tissues of female or male worms, with most prominence of gender differences in intestinal tissue. A. suum genes from the same family were frequently expressed differently among tissues. Transcript abundance for genes specific to A. suum, by comparison to Caenorhabditis elegans, varied to a greater extent among tissues than for genes conserved between A. suum and C. elegans. Analysis using C. elegans protein interaction data identified functional modules conserved between these two nematodes, resulting in identification of functional predictions of essential subnetworks of protein interactions and how these networks may vary among nematode tissues. A notable finding was very high module similarity between adult reproductive tissues and intestine. Our results provide the most comprehensive assessment of gene expression among tissues of a parasitic nematode to date. PMID:23572074

Wang, Zhengyuan; Gao, Xin; Martin, John; Yin, Yong; Abubucker, Sahar; Rash, Amy C; Li, Ben-Wen; Nash, Bill; Hallsworth-Pepin, Kym; Jasmer, Douglas P; Mitreva, Makedonka

2013-04-10

56

Transient expression of ?C1 protein differentially regulates host genes related to stress response, chloroplast and mitochondrial functions  

PubMed Central

Background Geminiviruses are emerging plant pathogens that infect a wide variety of crops including cotton, cassava, vegetables, ornamental plants and cereals. The geminivirus disease complex consists of monopartite begomoviruses that require betasatellites for the expression of disease symptoms. These complexes are widespread throughout the Old World and cause economically important diseases on several crops. A single protein encoded by betasatellites, termed ?C1, is a suppressor of gene silencing, inducer of disease symptoms and is possibly involved in virus movement. Studies of the interaction of ?C1 with hosts can provide useful insight into virus-host interactions and aid in the development of novel control strategies. We have used the differential display technique to isolate host genes which are differentially regulated upon transient expression of the ?C1 protein of chili leaf curl betasatellite (ChLCB) in Nicotiana tabacum. Results Through differential display analysis, eight genes were isolated from Nicotiana tabacum, at two and four days after infitration with ?C1 of ChLCB, expressed under the control of the Cauliflower mosaic virus 35S promoter. Cloning and sequence analysis of differentially amplified products suggested that these genes were involved in ATP synthesis, and acted as electron carriers for respiration and photosynthesis processes. These differentially expressed genes (DEGs) play an important role in plant growth and development, cell protection, defence processes, replication mechanisms and detoxification responses. Kegg orthology based annotation system analysis of these DEGs demonstrated that one of the genes, coding for polynucleotide nucleotidyl transferase, is involved in purine and pyrimidine metabolic pathways and is an RNA binding protein which is involved in RNA degradation. Conclusion ?C1 differentially regulated genes are mostly involved in chloroplast and mitochondrial functions. ?C1 also increases the expression of those genes which are involved in purine and pyrimidine metabolism. This information gives a new insight into the interaction of ?C1 with the host and can be used to understand host-virus interactions in follow-up studies.

2010-01-01

57

Ionotropic glutamate receptor gene GRIK3 SER310ALA functional polymorphism is related to delirium tremens in alcoholics  

Microsoft Academic Search

Upregulation of glutamatergic neurotransmission resulting from chronic ethanol intoxication may cause a hyperexcitable state during alcohol withdrawal, which may lead to seizures and delirium tremens. The aim of our study was to evaluate the association between a history of alcohol withdrawal-induced seizures and delirium tremens, and a functional polymorphism (Ser310Ala) of the GRIK3 gene coding for the glutamatergic kainate receptor

U W Preuss; P Zill; G Koller; B Bondy; V Hesselbrock; M Soyka

2006-01-01

58

Relation of Candidate Genes that Encode for Endothelial Function to Migraine and Stroke: The Stroke Prevention in Young Women Study  

PubMed Central

Background and Purpose Migraine with aura is a risk factor for ischemic stroke but the mechanism by which these disorders are associated remains unclear. Both disorders exhibit familial clustering, which may imply a genetic influence on migraine and stroke risk. Genes encoding for endothelial function are promising candidate genes for migraine and stroke susceptibility because of the importance of endothelial function in regulating vascular tone and cerebral blood flow. Methods Using data from the Stroke Prevention in Young Women (SPYW) study, a population-based case-control study including 297 women aged 15–49 years with ischemic stroke and 422 women without stroke, we evaluated whether polymorphisms in genes regulating endothelial function, including endothelin-1 (EDN), endothelin receptor type B (EDNRB), and nitric oxide synthase-3 (NOS3), confer susceptibility to migraine and stroke. Results EDN SNPs rs1800542 and rs10478723 were associated with increased stroke susceptibility in Caucasians, (OR = 2.1 (95% CI, 1.1 to 4.2) and OR = 2.2 (95% CI, 1.1 to 4.4); p = 0.02 and 0.02, respectively) as were EDNRB SNPs rs4885493 and rs10507875, (OR = 1.7 (95% CI, 1.1 to 2.7) and OR = 2.4 (95% CI, 1.4 to 4.3); p = 0.01 and 0.002, respectively). Only one of the tested SNPs (NOS3 - rs3918166) was associated with both migraine and stroke. Conclusions In our study population, variants in EDN and EDNRB were associated with stroke susceptibility in Caucasian but not in African-American women. We found no evidence that these genes mediate the association between migraine and stroke.

MacClellan, Leah R.; Howard, Timothy D.; Cole, John W.; Stine, O. Colin; Giles, Wayne H.; O'Connell, Jeffery R.; Wozniak, Marcella A.; Stern, Barney J.; Mitchell, Braxton D.; Kittner, Steven J.

2009-01-01

59

Possible Regulatory Roles of Promoter G-Quadruplexes in Cardiac Function-Related Genes - Human TnIc as a Model  

PubMed Central

G-quadruplexes (G4s) are four-stranded DNA secondary structures, which are involved in a diverse range of biological processes. Although the anti-cancer potential of G4s in oncogene promoters has been thoroughly investigated, the functions of promoter G4s in non-cancer-related genes are not well understood. We have explored the possible regulatory roles of promoter G4s in cardiac function-related genes using both computational and a wide range of experimental approaches. According to our bioinformatics results, it was found that potential G4-forming sequences are particularly enriched in the transcription regulatory regions (TRRs) of cardiac function-related genes. Subsequently, the promoter of human cardiac troponin I (TnIc) was chosen as a model, and G4s found in this region were subjected to biophysical characterisations. The chromosome 19 specific minisatellite G4 sequence (MNSG4) and near transcription start site (TSS) G4 sequence (?80 G4) adopt anti-parallel and parallel structures respectively in 100 mM KCl, with stabilities comparable to those of oncogene G4s. It was also found that TnIc G4s act cooperatively as enhancers in gene expression regulation in HEK293 cells, when stabilised by a synthetic G4-binding ligand. This study provides the first evidence of the biological significance of promoter G4s in cardiac function-related genes. The feasibility of using a single ligand to target multiple G4s in a particular gene has also been discussed.

Zhou, Wenhua; Suntharalingam, Kogularamanan; Brand, Nigel J.; Barton, Paul J. R.; Vilar, Ramon; Ying, Liming

2013-01-01

60

Human Cripto-Related Gene.  

National Technical Information Service (NTIS)

The invention relates, in general, to a human CRIPTO-related gene. In particular, the invention relates to a DNA segment encoding a human CRIPTO-related gene; polypeptides encoded by said DNA segment; recombinant DNA molecules containing the DNA segment; ...

D. Salomom M. Persico

1991-01-01

61

Expression of vasa ( vas)-related genes in germ cells and specific interference with gene functions by double-stranded RNA in the monogenean, Neobenedenia girellae  

Microsoft Academic Search

Neobenedenia girellae, a monogenean, is an important pathogen in marine cultured fish such as yellowtail and amberjack. An effective control method is required but none has yet been established. Aiming to establish a new control method by interfering with the gametogenesis of N. girellae, we focused on vasa (vas)-related genes that are expressed exclusively in the germline granules in Drosophila,

Hiroshi Ohashi; Naoko Umeda; Noritaka Hirazawa; Yuichi Ozaki; Chiemi Miura; Takeshi Miura

2007-01-01

62

Relating genes to function: identifying enriched transcription factors using the ENCODE ChIP-Seq significance tool  

PubMed Central

Motivation: Biological analysis has shifted from identifying genes and transcripts to mapping these genes and transcripts to biological functions. The ENCODE Project has generated hundreds of ChIP-Seq experiments spanning multiple transcription factors and cell lines for public use, but tools for a biomedical scientist to analyze these data are either non-existent or tailored to narrow biological questions. We present the ENCODE ChIP-Seq Significance Tool, a flexible web application leveraging public ENCODE data to identify enriched transcription factors in a gene or transcript list for comparative analyses. Implementation: The ENCODE ChIP-Seq Significance Tool is written in JavaScript on the client side and has been tested on Google Chrome, Apple Safari and Mozilla Firefox browsers. Server-side scripts are written in PHP and leverage R and a MySQL database. The tool is available at http://encodeqt.stanford.edu. Contact: abutte@stanford.edu Supplementary information: Supplementary material is available at Bioinformatics online.

Auerbach, Raymond K.; Chen, Bin; Butte, Atul J.

2013-01-01

63

Differential regulation of gene products in newly synthesized Brassica napus allotetraploids is not related to protein function nor subcellular localization  

Microsoft Academic Search

Background  Allopolyploidy is a preeminent process in plant evolution that results from the merger of distinct genomes in a common nucleusviainter-specific hybridization. Allopolyploid formation is usually related to genome-wide structural and functional changes\\u000a though the underlying mechanisms operating during this \\

Warren Albertin; Karine Alix; Thierry Balliau; Philippe Brabant; Marlčne Davanture; Christian Malosse; Benoît Valot; Hervé Thiellement

2007-01-01

64

DEFOG: Discrete Enrichment of Functionally Organized Genes  

PubMed Central

High-throughput biological experiments commonly result in a list of genes or proteins of interest. In order to understand the observed changes of the genes and to generate new hypotheses, one needs to understand the functions and roles of the genes and how those functions relate to the experimental conditions. Typically, statistical tests are performed in order to detect enriched Gene Ontology categories or Pathways, i.e. the categories are observed in the genes of interest more often than is expected by chance. Depending on the number of genes and the complexity and quantity of functions in which they are involved, such an analysis can easily result in hundreds of enriched terms. To this end we developed DEFOG, a web-based application that facilitates the functional analysis of gene sets by hierarchically organizing the genes into functionally related modules. Our computational pipeline utilizes three powerful tools to achieve this goal: (1) GeneMANIA creates a functional consensus network of the genes of interest based on gene-list-specific data fusion of hundreds of genomic networks from publicly available sources; (2) Transitivity Clustering organizes those genes into a clear hierarchy of functionally related groups, and (3) Ontologizer performs a Gene Ontology enrichment analysis on the resulting gene clusters. DEFOG integrates this computational pipeline within an easy-to-use web interface, thus allowing for a novel visual analysis of gene sets that aids in the discovery of potentially important biological mechanisms and facilitates the creation of new hypotheses. DEFOG is available at http://www.mooneygroup.org/defog.

Wittkop, Tobias; Berman, Ari E.; Fleisch, K. Mathew; Mooney, Sean D.

2012-01-01

65

Identification of diterpene biosynthetic gene clusters and functional analysis of labdane-related diterpene cyclases in Phomopsis amygdali.  

PubMed

Two diterpene biosynthesis gene clusters in the fusicoccin-producing fungus, Phomopsis amygdali, were identified by genome walking from PaGGS1 and PaGGS4 which encode the geranylgeranyl diphosphate (GGDP) synthases. The diterpene cyclase-like genes, PaDC1 and PaDC2, were respectively located proximal to PaGGS1 and PaGGS4. The amino acid sequences of these two enzymes were similar to those of fungal labdane-related diterpene cyclases. Recombinant PaDC1 converted GGDP mainly into phyllocladan-16 alpha-ol via (+)-copalyl diphosphate (CDP) and trace amounts of several labdane-related hydrocarbons which had been identified from the P. amygdali F6 mycelia. Since phyllocladan-16 alpha-ol had not been identified in P. amygdali F6 mycelia, we isolated phyllocladan-16 alpha-ol from the mycelia. Recombinant PaDC2 converted GGDP into (+)-CDP. Furthermore, we isolated the novel diterpenoid, phyllocladan-11 alpha,16 alpha,18-triol, which is a possible metabolite of phyllocladan-16 alpha-ol in the mycelia. We propose that genome walking offers a useful strategy for the discovery of novel natural products in fungi. PMID:18391465

Toyomasu, Tomonobu; Niida, Rie; Kenmoku, Hiromichi; Kanno, Yuri; Miura, Shigeyoshi; Nakano, Chiaki; Shiono, Yoshihito; Mitsuhashi, Wataru; Toshima, Hiroaki; Oikawa, Hideaki; Hoshino, Tsutomu; Dairi, Tohru; Kato, Nobuo; Sassa, Takeshi

2008-04-07

66

The fate of duplicated genes: loss or new function?  

Microsoft Academic Search

Summary Gene duplication events are important sources of novel gene functions. However, more often than not, a duplicate gene may lose its function and become a pseudogene. What is the relative frequency of these two scenarios: functional divergence versus gene loss? Given that most non-neutral mutations are deleteri- ous, gene loss should be far more frequent than divergence. However, a

Andreas Wagner

1998-01-01

67

Lack of association between a functional variant of the BRCA-1 related associated protein (BRAP) gene and ischemic stroke  

PubMed Central

Background Atherosclerosis shares common pathogenic features with myocardial infarction (MI) and ischemic stroke. BRCA-1 associated protein (BRAP), a newly identified risk gene for MI, aggravates the inflammatory response in atherosclerosis. The aim of this study was to test the association between the BRAP gene and stroke in a Taiwanese population. Methods A total of 1,074 stroke patients and 1,936 controls were genotyped for the functional SNP rs11066001. In our previous studies, the rare allele of this SNP has been repeatedly shown to exert a recessive effect. Therefore, in the current study, we tested for the same recessive model. First, the genotype distributions between all the controls and all the stroke cases were compared. Then to reduce heterogeneity, we explored several population subsets by selecting young stroke subjects (using 45 years of age as the cutoff point), age- and sex-comparable controls, plaque-free controls, and stroke subtypes. Results We did not find any significant association for the entire data set (OR = 0.94, p = 0.74) or for the subset analyses using age- and sex-comparable controls (p = 0.70) and plaque-free controls (p = 0.91). Analyses of the four stroke subtypes also failed to show any significant associations (p = 0.42 – 0.98). For both young and old subjects, the GG genotype of rs11066001 was similar in the stroke cases and unmatched controls (8.1% vs. 9.4% in young subjects and 8.0% vs. 7.8% in old subjects). Comparing stroke cases with plaque-free controls also failed to find any significant association. Conclusions The BRAP polymorphism may not play an important role in ischemic stroke in the studied population.

2013-01-01

68

FunGene: the functional gene pipeline and repository  

PubMed Central

Ribosomal RNA genes have become the standard molecular markers for microbial community analysis for good reasons, including universal occurrence in cellular organisms, availability of large databases, and ease of rRNA gene region amplification and analysis. As markers, however, rRNA genes have some significant limitations. The rRNA genes are often present in multiple copies, unlike most protein-coding genes. The slow rate of change in rRNA genes means that multiple species sometimes share identical 16S rRNA gene sequences, while many more species share identical sequences in the short 16S rRNA regions commonly analyzed. In addition, the genes involved in many important processes are not distributed in a phylogenetically coherent manner, potentially due to gene loss or horizontal gene transfer. While rRNA genes remain the most commonly used markers, key genes in ecologically important pathways, e.g., those involved in carbon and nitrogen cycling, can provide important insights into community composition and function not obtainable through rRNA analysis. However, working with ecofunctional gene data requires some tools beyond those required for rRNA analysis. To address this, our Functional Gene Pipeline and Repository (FunGene; http://fungene.cme.msu.edu/) offers databases of many common ecofunctional genes and proteins, as well as integrated tools that allow researchers to browse these collections and choose subsets for further analysis, build phylogenetic trees, test primers and probes for coverage, and download aligned sequences. Additional FunGene tools are specialized to process coding gene amplicon data. For example, FrameBot produces frameshift-corrected protein and DNA sequences from raw reads while finding the most closely related protein reference sequence. These tools can help provide better insight into microbial communities by directly studying key genes involved in important ecological processes.

Fish, Jordan A.; Chai, Benli; Wang, Qiong; Sun, Yanni; Brown, C. Titus; Tiedje, James M.; Cole, James R.

2013-01-01

69

FunGene: the functional gene pipeline and repository.  

PubMed

Ribosomal RNA genes have become the standard molecular markers for microbial community analysis for good reasons, including universal occurrence in cellular organisms, availability of large databases, and ease of rRNA gene region amplification and analysis. As markers, however, rRNA genes have some significant limitations. The rRNA genes are often present in multiple copies, unlike most protein-coding genes. The slow rate of change in rRNA genes means that multiple species sometimes share identical 16S rRNA gene sequences, while many more species share identical sequences in the short 16S rRNA regions commonly analyzed. In addition, the genes involved in many important processes are not distributed in a phylogenetically coherent manner, potentially due to gene loss or horizontal gene transfer. While rRNA genes remain the most commonly used markers, key genes in ecologically important pathways, e.g., those involved in carbon and nitrogen cycling, can provide important insights into community composition and function not obtainable through rRNA analysis. However, working with ecofunctional gene data requires some tools beyond those required for rRNA analysis. To address this, our Functional Gene Pipeline and Repository (FunGene; http://fungene.cme.msu.edu/) offers databases of many common ecofunctional genes and proteins, as well as integrated tools that allow researchers to browse these collections and choose subsets for further analysis, build phylogenetic trees, test primers and probes for coverage, and download aligned sequences. Additional FunGene tools are specialized to process coding gene amplicon data. For example, FrameBot produces frameshift-corrected protein and DNA sequences from raw reads while finding the most closely related protein reference sequence. These tools can help provide better insight into microbial communities by directly studying key genes involved in important ecological processes. PMID:24101916

Fish, Jordan A; Chai, Benli; Wang, Qiong; Sun, Yanni; Brown, C Titus; Tiedje, James M; Cole, James R

2013-10-01

70

Startle response related genes  

Microsoft Academic Search

The startle reaction (also known as the startle response, the startle reflex, or the alarm reaction) is the psychological and physiological response to a sudden unexpected stimulus, such as a flash of light, a loud noise (acoustic startle reflex), or a quick movement near the face. Abnormalities of startle response have been observed in many stress-related mental disorders, such as

Lei Zhang; Xian-Zhang Hu; He Li; Xiaoxia Li; David M. Benedek; Robert Ursano

2011-01-01

71

The functional landscape of mouse gene expression  

Microsoft Academic Search

ABSTRACT: BACKGROUND: Large-scale quantitative analysis of transcriptional co-expression has been used to dissect regulatory networks and to predict the functions of new genes discovered by genome sequencing in model organisms such as yeast. Although the idea that tissue-specific expression is indicative of gene function in mammals is widely accepted, it has not been objectively tested nor compared with the related

Wen Zhang; Quaid D Morris; Richard Chang; Ofer Shai; Malina A Bakowski; Nicholas Mitsakakis; Naveed Mohammad; Mark D Robinson; Ralph Zirngibl; Eszter Somogyi; Nancy Laurin; Eftekhar Eftekharpour; Eric Sat; Jörg Grigull; Qun Pan; Wen-Tao Peng; Nevan Krogan; Jack Greenblatt; Michael Fehlings; Derek van der Kooy; Jane Aubin; Benoit G Bruneau; Janet Rossant; Benjamin J Blencowe; Brendan J Frey; Timothy R Hughes

2004-01-01

72

An investigation of modifying effects of single nucleotide polymorphisms in metabolism-related genes on the relationship between peripheral nerve function and mercury levels in urine and hair.  

PubMed

Mercury (Hg) is a potent neurotoxicant. We hypothesized that single nucleotide polymorphisms (SNPs) in genes coding glutathione-related proteins, selenoproteins and metallothioneins may modify the relationship of mercury biomarkers with changes in peripheral nerve function. Dental professionals (n=515) were recruited in 2009 and 2010. Sensory nerve function (onset latency, peak latency and amplitude) of the median, ulnar and sural nerves was recorded. Samples of urine, hair and DNA were collected. Covariates related to demographics, nerve function and elemental and methyl-mercury exposure were also collected. Subjects included 244 dentists (47.4%) and 269 non-dentists (52.2%; mostly dental hygienists and dental assistants). The mean mercury levels in urine (1.06 ?g/L) and hair (0.51 ?g/g) were not significantly different from the US general population (0.95 ?g/L and 0.47 ?g/g, respectively). In multivariate linear models predicting nerve function adjusting for covariates, only 3 out of a total of 504 models showed stable and statistically significant interaction of SNPs with mercury biomarkers. Overall, given the possibility of false positives, the results suggested little evidence of effect modification of the SNPs on the relationship between mercury biomarkers with peripheral nerve function at exposure levels that are relevant to the general US population. PMID:22236634

Wang, Yi; Goodrich, Jaclyn M; Werner, Robert; Gillespie, Brenda; Basu, Niladri; Franzblau, Alfred

2012-01-10

73

The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists  

PubMed Central

The DAVID Gene Functional Classification Tool uses a novel agglomeration algorithm to condense a list of genes or associated biological terms into organized classes of related genes or biology, called biological modules. This organization is accomplished by mining the complex biological co-occurrences found in multiple sources of functional annotation. It is a powerful method to group functionally related genes and terms into a manageable number of biological modules for efficient interpretation of gene lists in a network context.

Huang, Da Wei; Sherman, Brad T; Tan, Qina; Collins, Jack R; Alvord, W Gregory; Roayaei, Jean; Stephens, Robert; Baseler, Michael W; Lane, H Clifford; Lempicki, Richard A

2007-01-01

74

Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia  

PubMed Central

Background Schizophrenia is characterized by complex gene expression changes. The transcriptome alterations in the prefrontal cortex have been the subject of several recent postmortem studies which yielded both convergent and divergent findings. Methods To increase measurement precision, we used a custom-designed DNA microarray platform with long oligonucleotides and multiple probes with replicates. The platform was designed to assess the expression of >1,800 genes specifically chosen because of their hypothesized roles in the pathophysiology of schizophrenia. The gene expression differences in dorsolateral prefrontal cortex samples from 14 matched pairs of schizophrenia and control subjects were analyzed using two technical replicates and four data mining approaches. Results In addition to replicating many expression changes in synaptic, oligodendrocyte and signal transduction genes, we uncovered and validated a robust immune/chaperone transcript upregulation in the schizophrenia samples. Conclusions We speculate that the overexpression of SERPINA3, IFITM1, IFITM2, IFITM3, CHI3L1, MT2A, CD14, HSPB1, HSPA1B and HSPA1A in schizophrenia subjects represents a long-lasting and correlated signature of an early environmental insult during development that actively contributes to the pathophysiology of prefrontal dysfunction.

Arion, Dominique; Unger, Travis; Lewis, David A.; Levitt, Pat; Mirnics, Karoly

2007-01-01

75

Closely Related Archaeal Haloarcula hispanica Icosahedral Viruses HHIV-2 and SH1 Have Nonhomologous Genes Encoding Host Recognition Functions  

PubMed Central

Studies on viral capsid architectures and coat protein folds have revealed the evolutionary lineages of viruses branching to all three domains of life. A widespread group of icosahedral tailless viruses, the PRD1-adenovirus lineage, was the first to be established. A double ?-barrel fold for a single major capsid protein is characteristic of these viruses. Similar viruses carrying genes coding for two major capsid proteins with a more complex structure, such as Thermus phage P23-77 and haloarchaeal virus SH1, have been isolated. Here, we studied the host range, life cycle, biochemical composition, and genomic sequence of a new isolate, Haloarcula hispanica icosahedral virus 2 (HHIV-2), which resembles SH1 despite being isolated from a different location. Comparative analysis of these viruses revealed that their overall architectures are very similar except that the genes for the receptor recognition vertex complexes are unrelated even though these viruses infect the same hosts.

Jaakkola, Salla T.; Penttinen, Reetta K.; Vilen, Silja T.; Jalasvuori, Matti; Ronnholm, Gunilla; Bamford, Jaana K. H.; Bamford, Dennis H.

2012-01-01

76

The utility of functional gene arrays for assessing community composition, relative abundance, and distribution of ammonia-oxidizing bacteria and archaea.  

PubMed

Ammonia-oxidizing bacteria (AOB) and archaea (AOA) transform ammonium to nitrite, an essential step in the complete mineralization of organic matter, leading to the accumulation of nitrate in oxic environments. The diversity and community composition of both groups have been extensively explored by sequence analysis of both 16S rRNA and amoA (encoding the critical enzyme, ammonia monooxygenase subunit A) genes. In this chapter, the power of the amoA gene as a phylogenetic marker for both AOB and AOA is extended to the development and application of DNA microarrays. Functional gene microarrays provide high throughput, relatively high resolution data on community composition and relative abundance, which is especially useful for comparisons among environments, and between samples in time and space, targeting the microbial group that is responsible for a biogeochemical transformation of interest, such as nitrification. In this chapter, the basic approaches to the design of probes to represent the target groups AOB and AOA are described, and the protocols for preparing hybridization targets from environmental samples are provided. Factors that influence the hybridization results and determine the sensitivity and specificity of the assays are discussed. A few examples of recent applications of amoA microarrays to explore temporal and spatial patterns in AOB and AOA community composition in estuaries and the ocean are presented. Array data are lower resolution than sequencing, but much higher throughput, thus allowing robust statistics and reproducibility that are not possible with large clone libraries. For specific functional groups, arrays provide more direct information in a more economical format than is possible with next generation sequencing. PMID:21514472

Ward, B B; Bouskill, N J

2011-01-01

77

Mining phenotypes for gene function prediction  

PubMed Central

Background Health and disease of organisms are reflected in their phenotypes. Often, a genetic component to a disease is discovered only after clearly defining its phenotype. In the past years, many technologies to systematically generate phenotypes in a high-throughput manner, such as RNA interference or gene knock-out, have been developed and used to decipher functions for genes. However, there have been relatively few efforts to make use of phenotype data beyond the single genotype-phenotype relationships. Results We present results on a study where we use a large set of phenotype data – in textual form – to predict gene annotation. To this end, we use text clustering to group genes based on their phenotype descriptions. We show that these clusters correlate well with several indicators for biological coherence in gene groups, such as functional annotations from the Gene Ontology (GO) and protein-protein interactions. We exploit these clusters for predicting gene function by carrying over annotations from well-annotated genes to other, less-characterized genes in the same cluster. For a subset of groups selected by applying objective criteria, we can predict GO-term annotations from the biological process sub-ontology with up to 72.6% precision and 16.7% recall, as evaluated by cross-validation. We manually verified some of these clusters and found them to exhibit high biological coherence, e.g. a group containing all available antennal Drosophila odorant receptors despite inconsistent GO-annotations. Conclusion The intrinsic nature of phenotypes to visibly reflect genetic activity underlines their usefulness in inferring new gene functions. Thus, systematically analyzing these data on a large scale offers many possibilities for inferring functional annotation of genes. We show that text clustering can play an important role in this process.

Groth, Philip; Weiss, Bertram; Pohlenz, Hans-Dieter; Leser, Ulf

2008-01-01

78

Isolation rearing induces social and emotional function abnormalities and alters glutamate and neurodevelopment-related gene expression in rats  

Microsoft Academic Search

Isolation rearing induces various cognitive abnormalities such as reversal learning deficits and reduced prepulse inhibition in rats. However, there are few reports in the literature on its effects on social and emotional functions. In the current study we aimed to address these issues and demonstrated that isolation rearing induced aggression and impaired social recognition, produced moderate anxiogenic effects in the

Xiaohong Zhao; Lei Sun; Hongxiao Jia; Qingxuan Meng; Si Wu; Nanxin Li; Shuchang He

2009-01-01

79

Hammondia hammondi, an avirulent relative of Toxoplasma gondii, has functional orthologs of known T. gondii virulence genes  

Technology Transfer Automated Retrieval System (TEKTRAN)

Toxoplasma gondii is a ubiquitous protozoan parasite capable of infecting all warm-blooded animals, including humans. Its closest extant relative, Hammondia hammondi, has never been found to infect humans and in contrast to T. gondii is highly attenuated in mice. To better understand the genetic bas...

80

Isolation rearing induces social and emotional function abnormalities and alters glutamate and neurodevelopment-related gene expression in rats.  

PubMed

Isolation rearing induces various cognitive abnormalities such as reversal learning deficits and reduced prepulse inhibition in rats. However, there are few reports in the literature on its effects on social and emotional functions. In the current study we aimed to address these issues and demonstrated that isolation rearing induced aggression and impaired social recognition, produced moderate anxiogenic effects in the elevated-plus maze, and resulted in hyperactivity in a novel open field. We also found NR2A, NR2B, PSD-95 and SAP-102 mRNA expression were significantly up-regulated in the hippocampus while NR2B was down-regulated in prefrontal cortex in response to isolation rearing. This study advances the use of social isolation as an animal model for studying etiological mechanisms of various neuropsychiatric disorders. PMID:19563853

Zhao, Xiaohong; Sun, Lei; Jia, Hongxiao; Meng, Qingxuan; Wu, Si; Li, Nanxin; He, Shuchang

2009-06-27

81

GOToolBox: functional analysis of gene datasets based on Gene Ontology  

Microsoft Academic Search

We have developed methods and tools based on the Gene Ontology (GO) resource allowing the identification of statistically over- or under-represented terms in a gene dataset; the clustering of functionally related genes within a set; and the retrieval of genes sharing annotations with a query gene. GO annotations can also be constrained to a slim hierarchy or a given level

David Martin; Christine Brun; Elisabeth Remy; Pierre Mouren; Denis Thieffry; Bernard Jacq

2004-01-01

82

Inference of the japonica rice domestication process from the distribution of six functional nucleotide polymorphisms of domestication-related genes in various landraces and modern cultivars.  

PubMed

Crop domestication can serve as a model of plant evolutionary processes. It involves a series of selection events from standing natural variation and newly occurring mutations and combinations of mutations as a result of natural crossings in populations during local adaptation and propagation of plant lines to other cultivation areas. Our earlier identification of three functional nucleotide polymorphisms (FNPs) of distinct genes involved in the rice domestication process led us to propose a model of the japonica rice domestication process. Here, we examined three more FNPs in two domestication-related genes involved in pigment synthesis during the development of seed pericarp color (Rc and Rd) in 91 landraces (and some modern cultivars) of japonica rice collected from throughout the area of distribution of rice. These polymorphisms were assigned by using genome-wide patterns of restriction fragment length polymorphisms (RFLPs) and the local origins of the landraces. The results led us to infer the process of japonica rice domestication in more detail and propose a more refined model of the japonica domestication process. In this model, the critical role of the Rc FNP at an early step of the domestication process was highlighted. Independent artificial selections of two defective Rd alleles were found, suggesting a role for Rd other than in pigment synthesis during rice domestication. PMID:18701522

Konishi, Saeko; Ebana, Kaworu; Izawa, Takeshi

2008-08-12

83

A novel functional low-density lipoprotein receptor-related protein 6 gene alternative splice variant is associated with Alzheimer's disease.  

PubMed

We previously found that single nucleotide polymorphisms in the low-density lipoprotein receptor-related protein 6 (LRP6) gene are associated with Alzheimer's disease (AD). Here, we studied the posttranscriptional metabolism of the LRP6 message scanning sequentially the 23 LRP6 exons in human tissues and found a novel LRP6 isoform that completely skips exon 3 (LRP6?3) in all tissues examined and was also conserved in mice. Expression levels of the LRP6 isoforms were determined in 47 cortical brain messenger (m)RNA samples including 22 AD cases, 11 control subjects, and 14 individuals with other neurological disorders. LRP6?3 mRNA levels were significantly augmented in AD brains compared with controls (1.6-fold; p = 0.037) or other pathological samples (2-fold; p = 0.007). Functional analysis in Wnt/?-catenin signaling assays revealed that skipping of exon 3 reduced significantly the signaling activity of the LRP6 coreceptor. We conclude that the LRP6?3 isoform is a novel splice variant, which shows diminished Wnt/?-catenin signaling activity and might have a functional role in individuals with AD. PMID:23218566

Alarcón, Marcelo A; Medina, Matías A; Hu, Qubai; Avila, Miguel E; Bustos, Bernabé I; Pérez-Palma, Eduardo; Peralta, Alexis; Salazar, Paulina; Ugarte, Giorgia D; Reyes, Ariel E; Martin, George M; Opazo, Carlos; Moon, Randall T; De Ferrari, Giancarlo V

2012-12-06

84

Spatial learning and memory function-related gene expression in the hippocampus of mouse exposed to nanoparticle-rich diesel exhaust.  

PubMed

Diesel exhaust particles are a major constituent of ambient particulate matter, and most particles emitted directly from diesel exhaust are smaller than 1microm in diameter. Recently, the toxicity of diesel engine-derived nanoparticles has come to be recognized as an emerging social issue. In the present study, we investigated spatial learning ability and memory function-related gene expressions in mouse hippocampus after the exposure of animals to nanoparticle-rich diesel exhaust (NRDE) with or without a bacterial cell wall component. Lipoteichoic acid (LTA), a cell wall component derived from Staphylococcus aureus, was used to induce systemic inflammation. Male BALB/c mice were exposed to clean air (particle concentration, 4.58microg/m(3)) or NRDE (148.86microg/m(3)) for 5h per day on 5 days of the week for 4 weeks in an exposure chamber, with or without the weekly intraperitoneal injection of LTA. On the day after the final day of exposure, we used a Morris water maze apparatus to examine the ability of the animals to perform a spatial learning task. After the completion of the test, the animals were sacrificed and the hippocampus was collected from each mouse; the expressions of NMDA receptor subunits (NR1, NR2A and NR2B), proinflammatory cytokines (IL-1beta and TNF-alpha) and the oxidative stress marker heme oxygenase 1 were then investigated using real-time RT-PCR. In the Morris water maze task, NRDE/LTA (+) group took a longer time to reach the hidden platform than clear air/LTA (-) group. However, NRDE exposure alone did not affect it. The relative mRNA levels of the NMDA receptor subunits and proinflammatory cytokines were higher in hippocampus of NRDE/LTA (+) group compared to clear air/LTA (-) group. These results indicate that co-exposure of NRDE and LTA could affect spatial learning and memory function-related gene expressions in mouse hippocampus. PMID:18926851

Win-Shwe, Tin-Tin; Yamamoto, Shoji; Fujitani, Yuji; Hirano, Seishiro; Fujimaki, Hidekazu

2008-09-24

85

LB-AUT7, a Novel Symbiosis-Regulated Gene from an Ectomycorrhizal Fungus, Laccaria bicolor, Is Functionally Related to Vesicular Transport and Autophagocytosis  

PubMed Central

We have identified LB-AUT7, a gene differentially expressed 6 h after ectomycorrhizal interaction between Laccaria bicolor and Pinus resinosa. LB-Aut7p can functionally complement its Saccharomyces cerevisiae homolog, which is involved in the attachment of autophagosomes to microtubules. Our findings suggest the induction of an autophagocytosis-like vesicular transport process during ectomycorrhizal interaction.

Kim, Sung-Jae; Bernreuther, Daniela; Thumm, Michael; Podila, Gopi K.

1999-01-01

86

Identifying gene functions using functional expression profiles obtained by voxelation  

Microsoft Academic Search

Gene expression profiles have been widely used in functional genomic studies. However, not much work in traditional gene expression profiling takes into account the location information of a gene's expressions in the brain. Gene expression maps, which contain spatial information regarding the expression of genes in mice's brain, are obtained by combining voxelation and microarrays. Based on the idea that

Li An; Desmond J. Smith; Hongbo Xie; Vasileios Megalooikonomou; Zoran Obradovic

2010-01-01

87

Population differences in major functional polymorphisms of pharmacokinetics/pharmacodynamics-related genes in Eastern Asians and Europeans: implications in the clinical trials for novel drug development.  

PubMed

Drug lag, recently discussed extensively in Japan, can be divided into two phases: clinical development time and application review time. The former factor is still an important problem that might be improved by promoting multi-regional clinical trials and considering the results from other similar populations with Japanese, such as Koreans and Chinese. In this review, we compare the allelic or genotype frequencies of 30 relatively common functional alleles mainly between Eastern Asians and Europeans as well as among 3 major populations in Eastern Asian countries, Japan, Korea, and China, in 12 pharmacokinetics (PK)/pharmacodynamics (PD)-related genes; CYP2C9 (*2 and *3), CYP2C19 (*2, *3 and *17), 13 CYP2D6 haplotypes including *4, *5 and *10, CYP3A5 (*3), UGT1A1 (*28 and *6), NAT2 (*5, *6 and *7), GSTM1 and GSTT1 null genotypes, SLCO1B1 521T>C, ABCG2 421C>A, and HLA-A*31:01 and HLA-B*58:01. In this review, differences in allele frequencies (AFs) or genotype frequencies (GFs) less than 0.1 (in the cases of highest AF (GF) ?0.1) or less than 0.05 (in the cases of lowest AF (GF) <0.1) were regarded as similar. Between Eastern Asians and Europeans, AFs (or GFs) are regarded as being different for many alleles such as CYP2C9 (*2), CYP2C19 (*2, *3 and *17), CYP2D6 (*4 and *10), CYP3A5 (*3), UGT1A1 (*28 and *6), NAT2 (*5*7), GSTT1 null and ABCG2 421C>A. Among the 3 Eastern Asian populations, however, only AFs of CYP2C19*3, CYP2D6*10, HLA-A*31:01 and HLA-B*58:01 are regarded as dissimilar. For CYP2C19*3, the total functional impact on CYP2C19 could be small if the frequencies of the two null alleles CYP2C19*2 and *3 are combined. Regarding CYP2D6*10, frequency difference over 0.1 is observed only between Japanese and Chinese (0.147). Although environmental factors should be considered for PK/PD differences, we could propose that among Japan, Korea, and China, genetic differences are very small for the analyzed common PK-related gene polymorphisms. On the other hand, AFs of the two HLA alleles important for cutaneous adverse drug reactions are diverse even among Eastern Asians and thus should be taken into account. PMID:22123129

Kurose, Kouichi; Sugiyama, Emiko; Saito, Yoshiro

2011-11-29

88

Analysis of Gene Order Conservation in Eukaryotes Identifies Transcriptionally and Functionally Linked Genes  

PubMed Central

The order of genes in eukaryotes is not entirely random. Studies of gene order conservation are important to understand genome evolution and to reveal mechanisms why certain neighboring genes are more difficult to separate during evolution. Here, genome-wide gene order information was compiled for 64 species, representing a wide variety of eukaryotic phyla. This information is presented in a browser where gene order may be displayed and compared between species. Factors related to non-random gene order in eukaryotes were examined by considering pairs of neighboring genes. The evolutionary conservation of gene pairs was studied with respect to relative transcriptional direction, intergenic distance and functional relationship as inferred by gene ontology. The results show that among gene pairs that are conserved the divergently and co-directionally transcribed genes are much more common than those that are convergently transcribed. Furthermore, highly conserved pairs, in particular those of fungi, are characterized by a short intergenic distance. Finally, gene pairs of metazoa and fungi that are evolutionary conserved and that are divergently transcribed are much more likely to be related by function as compared to poorly conserved gene pairs. One example is the ribosomal protein gene pair L13/S16, which is unusual as it occurs both in fungi and alveolates. A specific functional relationship between these two proteins is also suggested by the fact that they are part of the same operon in both eubacteria and archaea. In conclusion, factors associated with non-random gene order in eukaryotes include relative gene orientation, intergenic distance and functional relationships. It seems likely that certain pairs of genes are conserved because the genes involved have a transcriptional and/or functional relationship. The results also indicate that studies of gene order conservation aid in identifying genes that are related in terms of transcriptional control.

Davila Lopez, Marcela; Martinez Guerra, Juan Jose; Samuelsson, Tore

2010-01-01

89

Relational Descriptive Analysis of Gene Expression Data  

Microsoft Academic Search

This paper presents a method that uses gene ontologies, to- gether with the paradigm of relational subgroup discovery, to help nd description of groups of genes dieren tialy expressed in specic can- cers. The descriptions are represented by means of relational features, extracted from publicly available gene ontology information, and are straightforwardly interpretable by medical\\/biology researchers. We ap- plied the

Igor Trajkovski; Filip Zelezný; Nada Lavrac; Jakub Tolar

2006-01-01

90

Function of the DISC1 Gene  

NSDL National Science Digital Library

As a result of the human genome project, we now know largely where our genes are, and what structure they have. The search to uncover each gene's function, on the other hand, is only in its infancy. Functional genomics is an area of research dedicated to studying what protein is produced by a gene, and what happens in the body when it is activated. Understanding gene function is the next major hurdle in genomic research, which holds the key to developing revolutionary therapeutics.

2009-04-14

91

Presence, diversity and enumeration of functional genes (bssA and bamA) relating to toluene degradation across a range of redox conditions and inoculum sources.  

PubMed

The study investigates two functional genes for toluene degradation across three redox conditions (nitrate and sulfate amended and methanogenic). The genes targeted include benzylsuccinate synthase ?-subunit (bssA) and a gene recently identified as being a strong indicator of anaerobic aromatic degradation, called 6-oxocylcohex-1-ene-1-carbonyl-CoA hydrolase (bamA). In all, sixteen different anaerobic toluene degrading microcosms were investigated using several primers sets targeting bssA and one primer set targeting bamA. One bssA primer set (7772f/8546r) was the most successful in producing a strong amplicon (eight from sixteen) with the other bssA primers sets producing strong amplicons in six or less samples. In contrast, the bamA primer set (bam-sp9 and bam-asp1) produced a strong amplicon in DNA extracted from all except one microcosm. Partial bssA and bamA sequences were obtained for a number of samples and compared to those available in GenBank. The partial bssA sequences (from nitrate amended and methanogenic microcosms) were most similar to Thauera sp. DNT-1, Thauera aromatica, Aromatoleum aromaticum EbN1 and bssA clones from a study involving sulfate reducing toluene degradation. The bamA sequences obtained could be placed into five previously defined clades (bamA-clade 1, Georgfuchsia/Azoarcus, Magnetospirillum/Thauera Syntrophus and Geobacter clades), with the placement generally depending on redox conditions. Gene numbers were also correlated with toluene degradation and the final gene number for both genes differed considerably between the range of redox conditions. The work is the first in depth investigation of bamA diversity over a range of redox conditions and inoculum sources. PMID:23728713

Sun, Weimin; Sun, Xiaxuo; Cupples, Alison M

2013-06-01

92

Distribution of typical denitrifying functional genes and diversity of the nirS-encoding bacterial community related to environmental characteristics of river sediments  

NASA Astrophysics Data System (ADS)

Denitrification in river sediments leads to nitrate removal from the aquatic system; therefore, it is necessary to understand functional diversity of denitrifier communities in the system. Sediment samples (0-25 cm depth) were collected from three typical locations along the Pearl River. The real-time PCR approach was used to measure the abundance of nitrate (narG), nitrite (nirS, nirK and nrfA), and nitrous oxide (nosZ) reductase genes from the sediment samples. Assemblages of nirS, nirK and nosZ indicated that complete denitrification occurred in sediment cores, with the greatest number of gene copies from 5-15 cm depth. Dissimilatory nitrate reduction appeared to be important below 15 cm depth, based on increasing gene copies of narG and nrfA with sediment depth. There was a close match (78-94 %) between the nirS sequences recovered from Pearl River sediment and those detected in estuarine and marine sediments as well as active sludge, suggesting that domestic sewage inputs and irregular tides. Canonical correspondence analysis indicated that the spatial distribution of denitrifying bacteria was highly correlated with dissolved inorganic N (DIN: NH4+, NO2genes and the nirS-encoding denitrifier community in the river sediment. Our results also reveal a variety of novel denitrifying bacteria in the river sediment.

Huang, S.; Chen, C.; Wu, Q.; Zhang, R.; Yang, X.

2011-05-01

93

From single-SNP to wide-locus: genome-wide association studies identifying functionally related genes and intragenic regions in small sample studies  

PubMed Central

Background Genome-wide association studies (GWAS) have had limited success when applied to complex diseases. Analyzing SNPs individually requires several large studies to integrate the often divergent results. In the presence of epistasis, multivariate approaches based on the linear model (including stepwise logistic regression) often have low sensitivity and generate an abundance of artifacts. Methods Recent advances in distributed and parallel processing spurred methodological advances in nonparametric statistics. U-statistics for structured multivariate data (?Stat) are not confounded by unrealistic assumptions (e.g., linearity, independence). Results By incorporating knowledge about relationships between SNPs, ?GWAS (GWAS based on ?Stat) can identify clusters of genes around biologically relevant pathways and pinpoint functionally relevant regions within these genes. Conclusion With this computational biostatistics approach increasing power and guarding against artifacts, personalized medicine and comparative effectiveness will advance while subgroup analyses of Phase III trials can now suggest risk factors for ad verse events and novel directions for drug development.

Wittkowski, Knut M; Sonakya, Vikas; Song, Tingting; Seybold, Martin P; Keddache, Mehdi; Durner, Martina

2013-01-01

94

Novel Genes from Formation to Function  

PubMed Central

The study of the evolution of novel genes generally focuses on the formation of new coding sequences. However, equally important in the evolution of novel functional genes are the formation of regulatory regions that allow the expression of the genes and the effects of the new genes in the organism as well. Herein, we discuss the current knowledge on the evolution of novel functional genes, and we examine in more detail the youngest genes discovered. We examine the existing data on a very recent and rapidly evolving cluster of duplicated genes, the Sdic gene cluster. This cluster of genes is an excellent model for the evolution of novel genes, as it is very recent and may still be in the process of evolving.

Ponce, Rita; Martinsen, Lene; Vicente, Luis M.; Hartl, Daniel L.

2012-01-01

95

Distribution of typical denitrifying functional genes and diversity of the nirS-encoding bacterial community related to environmental characteristics of river sediments  

NASA Astrophysics Data System (ADS)

Denitrification in river sediments leads to nitrate removal from the aquatic system; therefore, it is necessary to understand functional diversity of denitrifier communities in the system. Sediment samples (0-25 cm depth) were collected from three typical locations along the Pearl River. The real-time PCR approach was used to measure the abundance of nitrate (narG), nitrite (nirS, nirK and nrfA), and nitrous oxide (nosZ) reductase genes from the sediment samples. Assemblages of nirS, nirK and nosZ indicated that complete denitrification occurred in sediment cores, with the greatest number of gene copies from 5-15 cm depth. Dissimilatory nitrate reduction appeared to be important below 15 cm depth, based on increasing gene copies of narG and nrfA with sediment depth. There was a close match (78-94 %) between the nirS sequences recovered from the Pearl River sediment and those detected in estuarine and marine sediments as well as active sludge, suggesting that the nitrogen source in the Pearl River sediment was affected by domestic sewage inputs and irregular tides. Canonical correspondence analysis indicated that the spatial distribution of denitrifying bacteria was highly correlated with dissolved inorganic nitrogen (including NH4+, NO2- and NO3-) concentrations in sediment. It was concluded that the difference in dissolved inorganic nitrogen concentrations along the sediment profile influenced the distribution of denitrifying genes and the nirS-encoding denitrifier community in the river sediment. In addition, a variety of novel denitrifying bacteria were revealed in the river sediment.

Huang, S.; Chen, C.; Yang, X.; Wu, Q.; Zhang, R.

2011-10-01

96

Functional analysis of the Trichoderma harzianum nox1 gene, encoding an NADPH oxidase, relates production of reactive oxygen species to specific biocontrol activity against Pythium ultimum.  

PubMed

The synthesis of reactive oxygen species (ROS) is one of the first events following pathogenic interactions in eukaryotic cells, and NADPH oxidases are involved in the formation of such ROS. The nox1 gene of Trichoderma harzianum was cloned, and its role in antagonism against phytopathogens was analyzed in nox1-overexpressed transformants. The increased levels of nox1 expression in these transformants were accompanied by an increase in ROS production during their direct confrontation with Pythium ultimum. The transformants displayed an increased hydrolytic pattern, as determined by comparing protease, cellulase, and chitinase activities with those for the wild type. In confrontation assays against P. ultimum the nox1-overexpressed transformants were more effective than the wild type, but not in assays against Botrytis cinerea or Rhizoctonia solani. A transcriptomic analysis using a Trichoderma high-density oligonucleotide (HDO) microarray also showed that, compared to gene expression for the interaction of wild-type T. harzianum and P. ultimum, genes related to protease, cellulase, and chitinase activities were differentially upregulated in the interaction of a nox1-overexpressed transformant with this pathogen. Our results show that nox1 is involved in T. harzianum ROS production and antagonism against P. ultimum. PMID:21421791

Montero-Barrientos, M; Hermosa, R; Cardoza, R E; Gutiérrez, S; Monte, E

2011-03-18

97

Functional Genes and Proteins of Clonorchis sinensis  

PubMed Central

During the past several decades, researches on parasite genetics have progressed from biochemical and serodiagnostic studies to protein chemistry, molecular biology, and functional gene studies. Nowadays, bioinformatics, genomics, and proteomics approaches are being applied by Korean parasitology researchers. As for Clonorchis sinensis, investigations have been carried out to identify its functional genes using forward and reverse genetic approaches and to characterize the biochemical and biological properties of its gene products. The authors review the proteins of cloned genes, which include antigenic proteins, physiologic and metabolic enzymes, and the gene expression profile of Clonorchis sinensis.

Kim, Tae Im; Na, Byoung-Kuk

2009-01-01

98

Analysis of the functions of recombination-related genes in the generation of large chromosomal deletions by loop-out recombination in Aspergillus oryzae.  

PubMed

Loop-out-type recombination is a type of intrachromosomal recombination followed by the excision of a chromosomal region. The detailed mechanism underlying this recombination and the genes involved in loop-out recombination remain unknown. In the present study, we investigated the functions of ku70, ligD, rad52, rad54, and rdh54 in the construction of large chromosomal deletions via loop-out recombination and the effect of the position of the targeted chromosomal region on the efficiency of loop-out recombination in Aspergillus oryzae. The efficiency of generation of large chromosomal deletions in the near-telomeric region of chromosome 3, including the aflatoxin gene cluster, was compared with that in the near-centromeric region of chromosome 8, including the tannase gene. In the ?ku70 and ?ku70-rdh54 strains, only precise loop-out recombination occurred in the near-telomeric region. In contrast, in the ?ligD, ?ku70-rad52, and ?ku70-rad54 strains, unintended chromosomal deletions by illegitimate loop-out recombination occurred in the near-telomeric region. In addition, large chromosomal deletions via loop-out recombination were efficiently achieved in the near-telomeric region, but barely achieved in the near-centromeric region, in the ?ku70 strain. Induction of DNA double-strand breaks by I-SceI endonuclease facilitated large chromosomal deletions in the near-centromeric region. These results indicate that ligD, rad52, and rad54 play a role in the generation of large chromosomal deletions via precise loop-out-type recombination in the near-telomeric region and that loop-out recombination between distant sites is restricted in the near-centromeric region by chromosomal structure. PMID:22286092

Takahashi, Tadashi; Ogawa, Masahiro; Koyama, Yasuji

2012-01-27

99

Analysis of the Functions of Recombination-Related Genes in the Generation of Large Chromosomal Deletions by Loop-Out Recombination in Aspergillus oryzae  

PubMed Central

Loop-out-type recombination is a type of intrachromosomal recombination followed by the excision of a chromosomal region. The detailed mechanism underlying this recombination and the genes involved in loop-out recombination remain unknown. In the present study, we investigated the functions of ku70, ligD, rad52, rad54, and rdh54 in the construction of large chromosomal deletions via loop-out recombination and the effect of the position of the targeted chromosomal region on the efficiency of loop-out recombination in Aspergillus oryzae. The efficiency of generation of large chromosomal deletions in the near-telomeric region of chromosome 3, including the aflatoxin gene cluster, was compared with that in the near-centromeric region of chromosome 8, including the tannase gene. In the ?ku70 and ?ku70-rdh54 strains, only precise loop-out recombination occurred in the near-telomeric region. In contrast, in the ?ligD, ?ku70-rad52, and ?ku70-rad54 strains, unintended chromosomal deletions by illegitimate loop-out recombination occurred in the near-telomeric region. In addition, large chromosomal deletions via loop-out recombination were efficiently achieved in the near-telomeric region, but barely achieved in the near-centromeric region, in the ?ku70 strain. Induction of DNA double-strand breaks by I-SceI endonuclease facilitated large chromosomal deletions in the near-centromeric region. These results indicate that ligD, rad52, and rad54 play a role in the generation of large chromosomal deletions via precise loop-out-type recombination in the near-telomeric region and that loop-out recombination between distant sites is restricted in the near-centromeric region by chromosomal structure.

Ogawa, Masahiro; Koyama, Yasuji

2012-01-01

100

Functional Genetic Polymorphisms in CYP2C19 Gene in Relation to Cardiac Side Effects and Treatment Dose in a Methadone Maintenance Cohort.  

PubMed

Abstract Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan. The steady-state plasma concentrations of both methadone and its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was significantly associated with the corrected QT interval (QTc) change in the electrocardiogram (p=0.021), and the Treatment Emergent Symptom Scale (TESS) total score (p=0.021) in patients who continued using heroin, as demonstrated with a positive urine opiate test. Using the gene dose (GD) models where the CYP2C19 SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and extensive (2 GD) metabolizers, we found that the extensive metabolizers required a higher dose of methadone (p=0.035), and showed a lower plasma R-methadone/methadone dose ratio (p=0.007) in urine opiate test negative patients, as well as a greater QTc change (p=0.008) and higher total scores of TESS (p=0.018) in urine opiate test positive patients, than poor metabolizers. These results in a large study sample from Taiwan suggest that the gene dose of CYP2C19 may potentially serve as an indicator for the plasma R-methadone/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy. Further studies of pharmacogenetic variation in methadone pharmacokinetics and pharmacodynamics are warranted in different world populations. PMID:24016178

Wang, Sheng-Chang; Ho, Ing-Kang; Tsou, Hsiao-Hui; Liu, Sheng-Wen; Hsiao, Chin-Fu; Chen, Chia-Hui; Tan, Happy Kuy-Lok; Lin, Linen; Wu, Chi-Shin; Su, Lien-Wen; Huang, Chieh-Liang; Yang, Yi-Hong; Liu, Ming-Lun; Lin, Keh-Ming; Liu, Shu Chih; Wu, Hsiao-Yu; Kuo, Hsiang-Wei; Chen, Andrew C H; Chang, Yao-Sheng; Liu, Yu-Li

2013-09-09

101

Identification and Functional Analysis of Light-Responsive Unique Genes and Gene Family Members in Rice  

Microsoft Academic Search

Functional redundancy limits detailed analysis of genes in many organisms. Here, we report a method to efficiently overcome this obstacle by combining gene expression data with analysis of gene-indexed mutants. Using a rice NSF45K oligo-microarray to compare 2-week-old light- and dark-grown rice leaf tissue, we identified 365 genes that showed significant 8-fold or greater induction in the light relative to

Ki-Hong Jung; Jinwon Lee; Chris Dardick; Young-Su Seo; Peijian Cao; Patrick Canlas; Jirapa Phetsom; Xia Xu; Shu Ouyang; Kyungsook An; Yun-Ja Cho; Geun-Cheol Lee; Yoosook Lee; Gynheung An; Pamela C. Ronald

2008-01-01

102

A protein required for RNA processing and splicing in Neurospora mitochondria is related to gene products involved in cell cycle protein phosphatase functions.  

PubMed

The Neurospora crassa cyt-4 mutants have pleiotropic defects in mitochondrial RNA splicing, 5' and 3' end processing, and RNA turnover. Here, we show that the cyt-4+ gene encodes a 120-kDa protein with significant similarity to the SSD1/SRK1 protein of Saccharomyces cerevisiae and the DIS3 protein of Schizosaccharomyces pombe, which have been implicated in protein phosphatase functions that regulate cell cycle and mitotic chromosome segregation. The CYT-4 protein is present in mitochondria and is truncated or deficient in two cyt-4 mutants. Assuming that the CYT-4 protein functions in a manner similar to the SSD1/SRK1 and DIS3 proteins, we infer that the mitochondrial RNA splicing and processing reactions defective in the cyt-4 mutants are regulated by protein phosphorylation and that the defects in the cyt-4 mutants result from failure to normally regulate this process. Our results provide evidence that RNA splicing and processing reactions may be regulated by protein phosphorylation. PMID:1311848

Turcq, B; Dobinson, K F; Serizawa, N; Lambowitz, A M

1992-03-01

103

Combining evidence, biomedical literature and statistical dependence: new insights for functional annotation of gene sets  

Microsoft Academic Search

BACKGROUND: Large-scale genomic studies based on transcriptome technologies provide clusters of genes that need to be functionally annotated. The Gene Ontology (GO) implements a controlled vocabulary organised into three hierarchies: cellular components, molecular functions and biological processes. This terminology allows a coherent and consistent description of the knowledge about gene functions. The GO terms related to genes come primarily from

Marc Aubry; Annabelle Monnier; Celine Chicault; Marie De Tayrac; Marie-dominique Galibert; Anita Burgun; Jean Mosser

2006-01-01

104

Full Length cDNA Cloning, Promoter Sequence, and Genomic Organization of the Human Adrenoleukodystrophy Related (ALDR) Gene Functionally Redundant to the Gene Responsible for X-Linked Adrenoleukodystrophy  

Microsoft Academic Search

X-linked adrenoleukodystrophy (X-ALD) is a functional defect of the ALD Protein (ALDP), an ABC half-transporter localized in the peroxisomal membrane. It is characterized by defective, very long chain fatty acid (VLCFA) ?-oxidation, resulting in progressive cerebral demyelination. Since individual mutations in the ALD gene may result in a variety of clinical phenotypes, the existence of modifying genetic factors has been

Andreas Holzinger; Peter Mayerhofer; Johannes Berger; Peter Lichtner; Stefan Kammerer; Adelbert A. Roscher

1999-01-01

105

Recursion Relations and Functional Equations for the Riemann Zeta Function  

Microsoft Academic Search

New recursion relations for the Riemann zeta function are introduced. Their derivation started from the standard functional equation. The new functional equations have both real and imaginary increment versions and can be applied over the whole complex plane. We have developed various versions of the recursion relations eliminating each of the coefficient functions, leaving plain zeta functions

Henrik Stenlund

2011-01-01

106

A method for finding communities of related genes  

PubMed Central

We present a method for creating a network of gene co-occurrences from the literature and partitioning it into communities of related genes. The way in which our method identifies communities makes it likely that the component genes of each community will be related by their function. The method processes a large database of article abstracts, synthesizing information from many sources to shed light on groups of genes that have been shown to interact. It is a tool to be used by researchers in the biomedical sciences to swiftly search for known interactions and to provide insight into unexplored connections. The partitioning procedure is designed to be particularly applicable to large networks in which individual nodes may play a role in more than one community. In this paper, we explain the details of the method, in particular the partitioning process. We also apply the method to produce communities of genes related to colon cancer and show that the results are useful.

Wilkinson, Dennis M.; Huberman, Bernardo A.

2004-01-01

107

Antagonistic functional duality of cancer genes.  

PubMed

Cancer evolution is a stochastic process both at the genome and gene levels. Most of tumors contain multiple genetic subclones, evolving in either succession or in parallel, either in a linear or branching manner, with heterogeneous genome and gene alterations, extensively rewired signaling networks, and addicted to multiple oncogenes easily switching with each other during cancer progression and medical intervention. Hundreds of discovered cancer genes are classified according to whether they function in a dominant (oncogenes) or recessive (tumor suppressor genes) manner in a cancer cell. However, there are many cancer "gene-chameleons", which behave distinctly in opposite way in the different experimental settings showing antagonistic duality. In contrast to the widely accepted view that mutant NADP(+)-dependent isocitrate dehydrogenases 1/2 (IDH1/2) and associated metabolite 2-hydroxyglutarate (R)-enantiomer are intrinsically "the drivers" of tumourigenesis, mutant IDH1/2 inhibited, promoted or had no effect on cell proliferation, growth and tumorigenicity in diverse experiments. Similar behavior was evidenced for dozens of cancer genes. Gene function is dependent on genetic network, which is defined by the genome context. The overall changes in karyotype can result in alterations of the role and function of the same genes and pathways. The diverse cell lines and tumor samples have been used in experiments for proving gene tumor promoting/suppressive activity. They all display heterogeneous individual karyotypes and disturbed signaling networks. Consequently, the effect and function of gene under investigation can be opposite and versatile in cells with different genomes that may explain antagonistic duality of cancer genes and the cell type- or the cellular genetic/context-dependent response to the same protein. Antagonistic duality of cancer genes might contribute to failure of chemotherapy. Instructive examples of unexpected activity of cancer genes and "paradoxical" effects of different anticancer drugs depending on the cellular genetic context/signaling network are discussed. PMID:23933273

Stepanenko, A A; Vassetzky, Y S; Kavsan, V M

2013-08-09

108

Functional identity of the gamma tropomyosin gene  

PubMed Central

The actin filament system is fundamental to cellular functions including regulation of shape, motility, cytokinesis, intracellular trafficking and tissue organization. Tropomyosins (Tm) are highly conserved components of actin filaments which differentially regulate filament stability and function. The mammalian Tm family consists of four genes; ?Tm, ?Tm, ?Tm and ?Tm. Multiple Tm isoforms (>40) are generated by alternative splicing and expression of these isoforms is highly regulated during development. In order to further identify the role of Tm isoforms during development, we tested the specificity of function of products from the ?Tm gene family in mice using a series of gene knockouts. Ablation of all ?Tm gene cytoskeletal products results in embryonic lethality. Elimination of just two cytoskeletal products from the ?Tm gene (NM1,2) resulted in a 50% reduction in embryo viability. It was also not possible to generate homozygous knockout ES cells for the targets which eliminated or reduced embryo viability in mice. In contrast, homozygous knockout ES cells were generated for a different set of isoforms (NM3,5,6,8,9,11) which were not required for embryogenesis. We also observed that males hemizygous for the knockout of all cytoskeletal products from the ?Tm gene preferentially transmitted the minus allele with 80–100% transmission. Since all four Tm genes are expressed in early embryos, ES cells and sperm, we conclude that isoforms of the ?Tm gene are functionally unique in their role in embryogenesis, ES cell viability and sperm function.

Hook, Jeff; Lemckert, Frances; Schevzov, Galina; Fath, Thomas

2011-01-01

109

VIRGO: computational prediction of gene functions.  

PubMed

Dramatic advances in sequencing technology and sophisticated experimental assays that interrogate the cell, combined with the public availability of the resulting data, herald the era of systems biology. However, the biological functions of more than 40% of the genes in sequenced genomes are unknown, posing a fundamental barrier to progress in systems biology. The large scale and diversity of available data requires the development of techniques that can automatically utilize these datasets to make quantified and robust predictions of gene function that can be experimentally verified. We present a service called the VIRtual Gene Ontology (VIRGO) that (i) constructs a functional linkage network (FLN) from gene expression and molecular interaction data, (ii) labels genes in the FLN with their functional annotations in the Gene Ontology and (iii) systematically propagates these labels across the FLN in order to precisely predict the functions of unlabelled genes. VIRGO assigns confidence estimates to predicted functions so that a biologist can prioritize predictions for further experimental study. For each prediction, VIRGO also provides an informative 'propagation diagram' that traces the flow of information in the FLN that led to the prediction. VIRGO is available at http://whipple.cs.vt.edu:8080/virgo. PMID:16845022

Massjouni, Naveed; Rivera, Corban G; Murali, T M

2006-07-01

110

Assembly of Inflammation-Related Genes for Pathway-Focused Genetic Analysis  

Microsoft Academic Search

Recent identifications of associations between novel variants in inflammation-related genes and several common diseases emphasize the need for systematic evaluations of these genes in disease susceptibility. Considering that many genes are involved in the complex inflammation responses and many genetic variants in these genes have the potential to alter the functions and expression of these genes, we assembled a list

Matthew J. Loza; Charles E. McCall; Liwu Li; William B. Isaacs; Jianfeng Xu; Bao-Li Chang; Jeffrey Gold

2007-01-01

111

Association of functional GITR gene polymorphisms related to expression of glucocorticoid-induced tumour necrosis factor-receptor (GITR) molecules with prognosis of autoimmune thyroid disease  

PubMed Central

The glucocorticoid-induced tumour necrosis factor (TNF)-receptor (GITR) affects the functions of regulatory T (Treg) and effector T (Teff) cells, but the significance of this phenomenon is still unclear. To examine the association of single nucleotide polymorphisms (SNPs) in the GITR gene with the expression of GITR molecules on T cells and with the pathological conditions in patients with autoimmune thyroid disease (AITD), we examined the frequencies of four candidate SNPs in AITD patients and healthy volunteers by restriction enzyme analysis and direct sequence analyses. We also analysed the GITR expression on peripheral Treg and Teff cells in AITD patients by three-colour flow cytometry. The CC genotype in the rs3753348 C/G SNP was significantly more frequent in patients with mild Hashimoto's disease (HD) than in those with severe HD [P = 0·0117, odds ratio (OR) = 3·13]. The AA genotype in the rs2298213 A/G SNP was significantly more frequent in patients with mild HD than in patients with severe HD (P = 0·010, OR = 4·43). All patients and healthy individuals had the GG genotype in rs60038293 A/G and rs11466696 A/G SNPs. The proportions of GITR+ cells in Treg and Teff cells were significantly higher in AITD patients with the CC genotype of the rs3753348 SNP than in those with the GG genotype (P = 0·004 and P = 0·011, respectively). In conclusion, the rs3753348 C/G SNP in the GITR is associated with HD prognosis and expression on Treg and Teff cells.

Tomizawa, R; Watanabe, M; Inoue, N; Takemura, K; Hidaka, Y; Akamizu, T; Hayakawa, K; Iwatani, Y

2011-01-01

112

The CDY-related gene family: coordinated evolution in copy number, expression profile and protein sequence  

Microsoft Academic Search

Theories predict that the long-term survival of duplicated genes requires their functional diversification, which can be accomplished by either subfunctionalization (the partitioning of ancestral functions among duplicates) or neofunctionalization (the acquisition of novel function). Here, we characterize the CDY-related mammalian gene family, focusing on three aspects of its evolution: gene copy number, tissue expression profile and amino acid sequence. We

Steve Dorus; Sandra L. Gilbert; Michele L. Forster; Robert J. Barndt; Bruce T. Lahn

2003-01-01

113

NOD1 gene polymorphisms in relation to aggressive periodontitis  

Microsoft Academic Search

Background: NOD proteins are part of innate immunity mechanisms. They play a role in epithelial barrier functions and inflammatory responses to bacteria. Single nucleotide polymorphisms (SNPs) in the NOD1 gene have proven to be associated with inflammatory bowel disease (IBD) and asthma.Objective: To investigate SNPs in the NOD1 gene in relation to aggressive periodontitis (AgP), a multifactorial, inflammatory disease of

B. G. Loos; A. Fiebig; M. Nothnagel; S. Jepsen; B. Groessner-Schreiber; A. Franke; P. M. Jervře-Storm; K. Schenck; U. van der Velden; S. Schreiber

2009-01-01

114

Cloning arbuscule-related genes from mycorrhizas  

Microsoft Academic Search

Until recently little was known about the identity of the genes expressed in the arbuscules of mycorrhizas, due in part to\\u000a problems associated with cloning genes from the tissues of an obligate symbiont. However, the combination of advanced molecular\\u000a techniques, innovative use of the materials available and fortuitous cloning has resulted in the recent identification of\\u000a a number of arbuscule-related

S. Burleigh

2000-01-01

115

Functional bias of positively selected genes in Streptococcus genomes  

PubMed Central

Rates of nonsynonymous substitution (dN) significantly higher than rates of synonymous substitution (dS) have been used as evidence of positive selection for the fixation of advantageous point mutations. It has been suggested that positive selection contributes to the evolution of virulence factors and certain functional categories in bacterial pathogens. The genus Streptococcus contains a number of important human and agricultural pathogens. Here we assessed positive selection across 13 Streptococcus species, and their relationship with virulence factors and functional categories. We found that known virulence genes were subject to positive selection pressure as much as other genes. After false discovery rate correction for multiple comparisons, no functional categories were significantly over- or underrepresented in positively selected genes relative to other genes. Our results suggest that within the genus Streptococcus positive selection based on dN/dS ratios is not distributed with bias across biological functions.

Suzuki, Haruo; Stanhope, Michael J.

2012-01-01

116

Genes for Chlorogenate and Hydroxycinnamate Catabolism (hca) Are Linked to Functionally Related Genes in the dca-pca-qui-pob-hca Chromosomal Cluster of Acinetobacter sp. Strain ADP1  

PubMed Central

Hydroxycinnamates are ubiquitous in the environment because of their contributions to the structure and defense mechanisms of plants. Additional plant products, many of which are formed in response to stress, support the growth of Acinetobacter sp. strain ADP1 through pathways encoded by genes in the dca-pca-qui-pob chromosomal cluster. In an appropriate genetic background, it was possible to select for an Acinetobacter strain that had lost the ability to grow with caffeate, a commonly occurring hydroxycinnamate. The newly identified mutation was shown to be a deletion in a gene designated hcaC and encoding a ligase required for conversion of commonly occurring hydroxycinnamates (caffeate, ferulate, coumarate, and 3,4-dihydroxyphenylpropionate) to thioesters. Linkage analysis showed that hcaC is linked to pobA. Downstream from hcaC and transcribed in the direction opposite the direction of pobA transcription are open reading frames designated hcaDEFG. Functions of these genes were inferred from sequence comparisons and from the properties of knockout mutants. HcaD corresponded to an acyl coenzyme A (acyl-CoA) dehydrogenase required for conversion of 3,4-dihydroxyphenylpropionyl-CoA to caffeoyl-CoA. HcaE appears to encode a member of a family of outer membrane proteins known as porins. Knockout mutations in hcaF confer no discernible phenotype. Knockout mutations in hcaG indicate that this gene encodes a membrane-associated esterase that hydrolyzes chlorogenate to quinate, which is metabolized in the periplasm, and caffeate, which is metabolized by intracellular enzymes. The chromosomal location of hcaG, between hcaC (required for growth with caffeate) and quiA (required for growth with quinate), provided the essential clue that led to the genetic test of HcaG as the esterase that produces caffeate and quinate from chlorogenate. Thus, in this study, organization within what is now established as the dca-pca-qui-pob-hca chromosomal cluster provided essential information about the function of genes in the environment.

Smith, Michael A.; Weaver, Valerie B.; Young, David M.; Ornston, L. Nicholas

2003-01-01

117

Drug target-gene signatures that predict teratogenicity are enriched for developmentally related genes  

PubMed Central

Drugs prescribed during pregnancy affect two populations simultaneously: fetuses and their mothers. Drug-induced fetal injury (teratogenicity) has a significant impact on current and future public health. Teratogenic risk designation of many drugs relies on associating rare fetal events with rare environmental exposures. Therefore we aim to develop preclinical predictive models of clinical teratogenicity. We collated public databases for drug-target-gene relationships for 619 drugs spanning the 5 pregnancy risk classes. Genes targeted by high risk but not low risk drugs demonstrated 79% accuracy (p<0.0001 vs. random) for predicting high vs. low fetal risk on cross validation. Functional enrichment analysis revealed that target genes of drugs known to be safe in pregnancy contained no developmentally related terms, while target genes of known teratogens contained 85 developmentally related terms. Drug target gene signatures that are enriched for known developmental genes may provide valuable preclinical predictive information regarding drug pregnancy risk.

Schachter, Asher D.; Kohane, Isaac S.

2010-01-01

118

HLA Immune Function Genes in Autism  

PubMed Central

The human leukocyte antigen (HLA) genes on chromosome 6 are instrumental in many innate and adaptive immune responses. The HLA genes/haplotypes can also be involved in immune dysfunction and autoimmune diseases. It is now becoming apparent that many of the non-antigen-presenting HLA genes make significant contributions to autoimmune diseases. Interestingly, it has been reported that autism subjects often have associations with HLA genes/haplotypes, suggesting an underlying dysregulation of the immune system mediated by HLA genes. Genetic studies have only succeeded in identifying autism-causing genes in a small number of subjects suggesting that the genome has not been adequately interrogated. Close examination of the HLA region in autism has been relatively ignored, largely due to extraordinary genetic complexity. It is our proposition that genetic polymorphisms in the HLA region, especially in the non-antigen-presenting regions, may be important in the etiology of autism in certain subjects.

Torres, Anthony R.; Westover, Jonna B.; Rosenspire, Allen J.

2012-01-01

119

Systematic prediction of gene function in Arabidopsis thaliana using a probabilistic functional gene network  

PubMed Central

AraNet is a functional gene network for the reference plant Arabidopsis and has been constructed in order to identify new genes associated with plant traits. It is highly predictive for diverse biological pathways and can be used to prioritize genes for functional screens. Moreover, AraNet provides a web-based tool with which plant biologists can efficiently discover novel functions of Arabidopsis genes (http://www.functionalnet.org/aranet/). This protocol explains how to conduct network-based prediction of gene functions using AraNet and how to interpret the prediction results. Functional discovery in plant biology is facilitated by combining candidate prioritization by AraNet with focused experimental tests.

Hwang, Sohyun; Rhee, Seung Y; Marcotte, Edward M; Lee, Insuk

2012-01-01

120

Convergence in pigmentation at multiple levels: mutations, genes and function.  

PubMed

Convergence--the independent evolution of the same trait by two or more taxa--has long been of interest to evolutionary biologists, but only recently has the molecular basis of phenotypic convergence been identified. Here, we highlight studies of rapid evolution of cryptic coloration in vertebrates to demonstrate that phenotypic convergence can occur at multiple levels: mutations, genes and gene function. We first show that different genes can be responsible for convergent phenotypes even among closely related populations, for example, in the pale beach mice inhabiting Florida's Gulf and Atlantic coasts. By contrast, the exact same mutation can create similar phenotypes in distantly related species such as mice and mammoths. Next, we show that different mutations in the same gene need not be functionally equivalent to produce similar phenotypes. For example, separate mutations produce divergent protein function but convergent pale coloration in two lizard species. Similarly, mutations that alter the expression of a gene in different ways can, nevertheless, result in similar phenotypes, as demonstrated by sister species of deer mice. Together these studies underscore the importance of identifying not only the genes, but also the precise mutations and their effects on protein function, that contribute to adaptation and highlight how convergence can occur at different genetic levels. PMID:20643733

Manceau, Marie; Domingues, Vera S; Linnen, Catherine R; Rosenblum, Erica Bree; Hoekstra, Hopi E

2010-08-27

121

Convergence in pigmentation at multiple levels: mutations, genes and function  

PubMed Central

Convergence—the independent evolution of the same trait by two or more taxa—has long been of interest to evolutionary biologists, but only recently has the molecular basis of phenotypic convergence been identified. Here, we highlight studies of rapid evolution of cryptic coloration in vertebrates to demonstrate that phenotypic convergence can occur at multiple levels: mutations, genes and gene function. We first show that different genes can be responsible for convergent phenotypes even among closely related populations, for example, in the pale beach mice inhabiting Florida's Gulf and Atlantic coasts. By contrast, the exact same mutation can create similar phenotypes in distantly related species such as mice and mammoths. Next, we show that different mutations in the same gene need not be functionally equivalent to produce similar phenotypes. For example, separate mutations produce divergent protein function but convergent pale coloration in two lizard species. Similarly, mutations that alter the expression of a gene in different ways can, nevertheless, result in similar phenotypes, as demonstrated by sister species of deer mice. Together these studies underscore the importance of identifying not only the genes, but also the precise mutations and their effects on protein function, that contribute to adaptation and highlight how convergence can occur at different genetic levels.

Manceau, Marie; Domingues, Vera S.; Linnen, Catherine R.; Rosenblum, Erica Bree; Hoekstra, Hopi E.

2010-01-01

122

Flik, a Chick Follistatin-Related Gene, Functions in Gastrular Dorsalisation\\/Neural Induction and in Subsequent Maintenance of Midline Sonic Hedgehog Signalling  

Microsoft Academic Search

We have targetted the chick gene Flik with antisense oligodeoxynucleotide treatment at gastrular stages, when it is expressed in organiser-derived structures of the midline (K. Patel et al., 1996, Dev. Biol. 178, 327–342). A specific syndrome of deficient axial patterning and holoprosencephaly is produced. Most aspects of this syndrome can be understood as due to attenuation of dorsalising and neural-inducing

Paula Towers; Ketan Patel; Sarah Withington; Alison Isaac; Jonathan Cooke

1999-01-01

123

Inflammation and neurological disease-related genes are differentially expressed in depressed patients with mood disorders and correlate with morphometric and functional imaging abnormalities.  

PubMed

Depressed patients show evidence of both proinflammatory changes and neurophysiological abnormalities such as increased amygdala reactivity and volumetric decreases of the hippocampus and ventromedial prefrontal cortex (vmPFC). However, very little is known about the relationship between inflammation and neuroimaging abnormalities in mood disorders. A whole genome expression analysis of peripheral blood mononuclear cells yielded 12 protein-coding genes (ADM, APBB3, CD160, CFD, CITED2, CTSZ, IER5, NFKBIZ, NR4A2, NUCKS1, SERTAD1, TNF) that were differentially expressed between 29 unmedicated depressed patients with a mood disorder (8 bipolar disorder, 21 major depressive disorder) and 24 healthy controls (HCs). Several of these genes have been implicated in neurological disorders and/or apoptosis. Ingenuity Pathway Analysis yielded two genes networks, one centered around TNF with NFK?, TGF?, and ERK as connecting hubs, and the second network indicating cell cycle and/or kinase signaling anomalies. fMRI scanning was conducted using a backward-masking task in which subjects were presented with emotionally-valenced faces. Compared with HCs, the depressed subjects displayed a greater hemodynamic response in the right amygdala, left hippocampus, and the ventromedial prefrontal cortex to masked sad versus happy faces. The mRNA levels of several genes were significantly correlated with the hemodynamic response of the amygdala, vmPFC and hippocampus to masked sad versus happy faces. Differentially-expressed transcripts were significantly correlated with thickness of the left subgenual ACC, and volume of the hippocampus and caudate. Our results raise the possibility that molecular-level immune dysfunction can be mapped onto macro-level neuroimaging abnormalities, potentially elucidating a mechanism by which inflammation leads to depression. PMID:23064081

Savitz, Jonathan; Frank, Mark Barton; Victor, Teresa; Bebak, Melissa; Marino, Julie H; Bellgowan, Patrick S F; McKinney, Brett A; Bodurka, Jerzy; Kent Teague, T; Drevets, Wayne C

2012-10-12

124

Computational identification of Cis-regulatory elements associated with groups of functionally related genes in Saccharomyces cerevisiae 1 1 Edited by F. E. Cohen  

Microsoft Academic Search

AlignACE is a Gibbs sampling algorithm for identifying motifs that are over-represented in a set of DNA sequences. When used to search upstream of apparently coregulated genes, AlignACE finds motifs that often correspond to the DNA binding preferences of transcription factors. We previously used AlignACE to analyze whole genome mRNA expression data. Here, we present a more detailed study of

Jason D Hughes; Preston W Estep; Saeed Tavazoie; George M Church

2000-01-01

125

High-throughput comparison of gene fitness among related bacteria  

PubMed Central

Background The contribution of a gene to the fitness of a bacterium can be assayed by whether and to what degree the bacterium tolerates transposon insertions in that gene. We use this fact to compare the fitness of syntenic homologous genes among related Salmonella strains and thereby reveal differences not apparent at the gene sequence level. Results A transposon Tn5 derivative was used to construct mutants in Salmonella Typhimurium ATCC14028 (STM1) and Salmonella Typhi Ty2 (STY1), which were then grown in rich media. The locations of 234,152 and 53,556 integration sites, respectively, were mapped by sequencing. These data were compared to similar data available for a different Ty2 isolate (STY2) and essential genes identified in E. coli K-12 (ECO). Of 277 genes considered essential in ECO, all had syntenic homologs in STM1, STY1, and STY2, and all but nine genes were either devoid of transposon insertions or had very few. For three of these nine genes, part of the annotated gene lacked transposon integrations (yejM, ftsN and murB). At least one of the other six genes, trpS, had a potentially functionally redundant gene encoded elsewhere in Salmonella but not in ECO. An additional 165 genes were almost entirely devoid of transposon integrations in all three Salmonella strains examined, including many genes associated with protein and DNA synthesis. Four of these genes (STM14_1498, STM14_2872, STM14_3360, and STM14_5442) are not found in E. coli. Notable differences in the extent of gene selection were also observed among the three different Salmonella isolates. Mutations in hns, for example, were selected against in STM1 but not in the two STY strains, which have a defect in rpoS rendering hns nonessential. Conclusions Comparisons among transposon integration profiles from different members of a species and among related species, all grown in similar conditions, identify differences in gene contributions to fitness among syntenic homologs. Further differences in fitness profiles among shared genes can be expected in other selective environments, with potential relevance for comparative systems biology.

2012-01-01

126

Functional gene-mining for salt-tolerance genes with the power of Arabidopsis  

PubMed Central

Summary Here we report on a functional gene-mining method developed to isolate stress tolerance genes without any prior knowledge of the genome or genetic mapping of the source germplasms. The feasibility of this approach was demonstrated by isolating novel salt stress tolerance genes from salt cress (Thellungiella halophila), an extremophile that is adapted to a harsh saline environment and a close relative of the model plant Arabidopsis thaliana. This gene-mining method is based on the expression of salt cress cDNA libraries in Arabidopsis. A cDNA expression library of the source germplasm, salt cress, was constructed and used to transform Arabidopsis via Agrobacterium-mediated gene transfer. A transgenic seed library consisting of >125 000 independent lines was generated and screened for salt-tolerant lines via a high-throughput genetic screen. A number of salt-tolerant lines were isolated, and the salt cress cDNAs were identified by PCR amplification and sequencing. Among the genes isolated, several novel small protein-encoding genes were discovered. The homologs of these genes in Arabidopsis have not been experimentally analyzed, and their functions remain unknown. The function of two genes isolated by this method, ST6-66 and ST225, and their Arabidopsis homologs, were investigated in Arabidopsis using gain- and loss-of-function analyses, and their importance in salt tolerance was demonstrated. Thus, our functional gene-mining method was validated by these results. Our method should be applicable for the functional mining of stress tolerance genes from various germplasms. Future improvements of the method are also discussed.

Du, Jin; Huang, Yue-Ping; Xi, Jing; Cao, Min-Jie; Ni, Wan-Song; Chen, Xi; Zhu, Jian-Kang; Oliver, David J.; Xiang, Cheng-Bin

2010-01-01

127

Conservation of gene function in behaviour  

PubMed Central

Behaviour genetic research has shown that a given gene or gene pathway can influence categorically similar behaviours in different species. Questions about the conservation of gene function in behaviour are increasingly tractable. This is owing to the surge of DNA and 'omics data, bioinformatic tools, as well as advances in technologies for behavioural phenotyping. Here, we discuss how gene function, as a hierarchical biological phenomenon, can be used to examine behavioural homology across species. The question can be addressed independently using different levels of investigation including the DNA sequence, the gene's position in a genetic pathway, spatial–temporal tissue expression and neural circuitry. Selected examples from the literature are used to illustrate this point. We will also discuss how qualitative and quantitative comparisons of the behavioural phenotype, its function and the importance of environmental and social context should be used in cross-species comparisons. We conclude that (i) there are homologous behaviours, (ii) they are hard to define and (iii) neurogenetics and genomics investigations should help in this endeavour.

Reaume, Christopher J.; Sokolowski, Marla B.

2011-01-01

128

Replication timing-related and gene body-specific methylation of active human genes.  

PubMed

Understanding how the epigenetic blueprint of the genome shapes human phenotypes requires systematic evaluation of the complex interplay between gene activity and the different layers of the epigenome. Utilizing microarray-based techniques, we explored the relationships between DNA methylation, DNA replication timing and gene expression levels across a variety of human tissues and cell lines. The analyses revealed unequal methylation levels among early- and late-replicating fractions of the genome: late-replicating DNA was hypomethylated compared with early-replicating DNA. Moreover, late-replicating regions were gradually demethylated with cell divisions, whereas the methylation of early-replicating regions was better maintained. As active genes concentrate at early-replicating regions, they are overall hypermethylated relative to inactive genes. Accordingly, we show that the previously reported positive correlation between gene-body methylation (methylation of the transcribed portion of genes) and gene expression is restricted to proliferative tissues and cell lines, whereas in tissues containing few proliferating cells, active and inactive genes have similar methylation levels. We further show that active gene bodies are hypermethylated not only compared with inactive gene bodies, but also compared with their flanking sequences. This specific hypermethylation of the active gene bodies is severely disrupted in cells of an immunodeficiency, centromeric region instability, facial anomalies (ICF) syndrome patient bearing mutated DNA methyltransferase 3B (DNMT3B). Our data show that a high methylation level is preferentially maintained in active gene bodies through independent cellular processes. Rather than serving as a distinctive mark between active and inactive genes, gene-body methylation appears to serve a vital, currently unknown function in active genes. PMID:21112978

Aran, Dvir; Toperoff, Gidon; Rosenberg, Michael; Hellman, Asaf

2010-11-26

129

Identification of Mycoparasitism-Related Genes in Trichoderma atroviride ? † ‡  

PubMed Central

A high-throughput sequencing approach was utilized to carry out a comparative transcriptome analysis of Trichoderma atroviride IMI206040 during mycoparasitic interactions with the plant-pathogenic fungus Rhizoctonia solani. In this study, transcript fragments of 7,797 Trichoderma genes were sequenced, 175 of which were host responsive. According to the functional annotation of these genes by KOG (eukaryotic orthologous groups), the most abundant group during direct contact was “metabolism.” Quantitative reverse transcription (RT)-PCR confirmed the differential transcription of 13 genes (including swo1, encoding an expansin-like protein; axe1, coding for an acetyl xylan esterase; and homologs of genes encoding the aspartyl protease papA and a trypsin-like protease, pra1) in the presence of R. solani. An additional relative gene expression analysis of these genes, conducted at different stages of mycoparasitism against Botrytis cinerea and Phytophthora capsici, revealed a synergistic transcription of various genes involved in cell wall degradation. The similarities in expression patterns and the occurrence of regulatory binding sites in the corresponding promoter regions suggest a possible analog regulation of these genes during the mycoparasitism of T. atroviride. Furthermore, a chitin- and distance-dependent induction of pra1 was demonstrated.

Reithner, Barbara; Ibarra-Laclette, Enrique; Mach, Robert L.; Herrera-Estrella, Alfredo

2011-01-01

130

Hepatocyte nuclear factor-1 alpha, GATA-4, and caudal related homeodomain protein Cdx2 interact functionally to modulate intestinal gene transcription. Implication for the developmental regulation of the sucrase-isomaltase gene.  

PubMed

Sucrase-isomaltase (SI), an intestine-specific gene, is induced in the differentiated small intestinal villous epithelium during the suckling-weaning transition in mice. We have previously identified cis-acting elements within a short evolutionarily conserved SI promoter. However, the nature and profile of expression of the interacting proteins have not been fully characterized during this developmental transition. Herein, we show that hepatocyte nuclear factor-1 alpha (HNF-1 alpha), GATA-4, and caudal related homeodomain proteins Cdx2 and Cdx1 are the primary transcription factors from the adult mouse intestinal epithelium to interact with the SIF3, GATA, and SIF1 elements of the SI promoter. We wanted to study whether HNF-1 alpha, GATA-4, and Cdx2 can cooperate in the regulation of SI gene expression. Immunolocalization experiments revealed that HNF-1 alpha is detected in rare epithelial cells of suckling mice and becomes progressively more expressed in the villous epithelial cells during the suckling-weaning transition. GATA-4 protein is expressed exclusively in villous differentiated epithelial cells of the proximal small intestine, decreases in expression in the ileum, and becomes undetectable in the colon. HNF-1 alpha, GATA-4, and Cdx2 interact in vitro and in vivo. These factors activate SI promoter activity in cotransfection experiments where GATA-4 requires the presence of both HNF-1 alpha and Cdx2. These findings imply a combinatory role of HNF-1 alpha, Cdx2, and GATA-4 for the time- and position-dependent regulation of SI transcription during development. PMID:12060663

Boudreau, François; Rings, Edmond H H M; van Wering, Herbert M; Kim, Richard K; Swain, Gary P; Krasinski, Stephen D; Moffett, Jennifer; Grand, Richard J; Suh, Eun Ran; Traber, Peter G

2002-06-11

131

Visually Relating Gene Expression and in vivo DNA Binding Data  

SciTech Connect

Gene expression and in vivo DNA binding data provide important information for understanding gene regulatory networks: in vivo DNA binding data indicate genomic regions where transcription factors are bound, and expression data show the output resulting from this binding. Thus, there must be functional relationships between these two types of data. While visualization and data analysis tools exist for each data type alone, there is a lack of tools that can easily explore the relationship between them. We propose an approach that uses the average expression driven by multiple of ciscontrol regions to visually relate gene expression and in vivo DNA binding data. We demonstrate the utility of this tool with examples from the network controlling early Drosophila development. The results obtained support the idea that the level of occupancy of a transcription factor on DNA strongly determines the degree to which the factor regulates a target gene, and in some cases also controls whether the regulation is positive or negative.

Huang, Min-Yu; Mackey, Lester; Ker?; nen, Soile V. E.; Weber, Gunther H.; Jordan, Michael I.; Knowles, David W.; Biggin, Mark D.; Hamann, Bernd

2011-09-20

132

Molecular and Functional Characterization of Broccoli EMBRYONIC FLOWER 2 Genes  

PubMed Central

Polycomb group (PcG) proteins regulate major developmental processes in Arabidopsis. EMBRYONIC FLOWER 2 (EMF2), the VEFS domain-containing PcG gene, regulates diverse genetic pathways and is required for vegetative development and plant survival. Despite widespread EMF2-like sequences in plants, little is known about their function other than in Arabidopsis and rice. To study the role of EMF2 in broccoli (Brassica oleracea var. italica cv. Elegance) development, we identified two broccoli EMF2 (BoEMF2) genes with sequence homology to and a similar gene expression pattern to that in Arabidopsis (AtEMF2). Reducing their expression in broccoli resulted in aberrant phenotypes and gene expression patterns. BoEMF2 regulates genes involved in diverse developmental and stress programs similar to AtEMF2 in Arabidopsis. However, BoEMF2 differs from AtEMF2 in the regulation of flower organ identity, cell proliferation and elongation, and death-related genes, which may explain the distinct phenotypes. The expression of BoEMF2.1 in the Arabidopsis emf2 mutant (Rescued emf2) partially rescued the mutant phenotype and restored the gene expression pattern to that of the wild type. Many EMF2-mediated molecular and developmental functions are conserved in broccoli and Arabidopsis. Furthermore, the restored gene expression pattern in Rescued emf2 provides insights into the molecular basis of PcG-mediated growth and development.

Chen, Long-Fang O.; Lin, Chun-Hung; Lai, Ying-Mi; Huang, Jia-Yuan; Sung, Zinmay Renee

2012-01-01

133

Mutualistic polydnaviruses share essential replication gene functions with pathogenic ancestors.  

PubMed

Viruses are usually thought to form parasitic associations with hosts, but all members of the family Polydnaviridae are obligate mutualists of insects called parasitoid wasps. Phylogenetic data founded on sequence comparisons of viral genes indicate that polydnaviruses in the genus Bracovirus (BV) are closely related to pathogenic nudiviruses and baculoviruses. However, pronounced differences in the biology of BVs and baculoviruses together with high divergence of many shared genes make it unclear whether BV homologs still retain baculovirus-like functions. Here we report that virions from Microplitis demolitor bracovirus (MdBV) contain multiple baculovirus-like and nudivirus-like conserved gene products. We further show that RNA interference effectively and specifically knocks down MdBV gene expression. Coupling RNAi knockdown methods with functional assays, we examined the activity of six genes in the MdBV conserved gene set that are known to have essential roles in transcription (lef-4, lef-9), capsid assembly (vp39, vlf-1), and envelope formation (p74, pif-1) during baculovirus replication. Our results indicated that MdBV produces a baculovirus-like RNA polymerase that transcribes virus structural genes. Our results also supported a conserved role for vp39, vlf-1, p74, and pif-1 as structural components of MdBV virions. Additional experiments suggested that vlf-1 together with the nudivirus-like gene int-1 also have novel functions in regulating excision of MdBV proviral DNAs for packaging into virions. Overall, these data provide the first experimental insights into the function of BV genes in virion formation. PMID:23671417

Burke, Gaelen R; Thomas, Sarah A; Eum, Jai H; Strand, Michael R

2013-05-09

134

Norrie disease gene: Characterization of deletions and possible function  

SciTech Connect

Positional cloning experiments have resulted recently in the isolation of a candidate gene for Norrie disease (pseudoglioma; NDP), a severe X-linked neuro-developmental disorder. Here the authors report the isolation and analysis of human genomic DNA clones encompassing the NDP gene. The gene spans 28 kb and consists of 3 exons, the first of which is entirely contained within the 5{prime} untranslated region. Detailed analysis of genomic deletions in Norrie patients shows that they are heterogeneous, both in size and in position. By PCR analysis, they found that expression of the NDP gene was not confined to the eye or to the brain. An extensive DNA and protein sequence comparison between the human NDP gene and related genes from the database revealed homology with cysteine-rich protein-binding domains of immediate--early genes implicated in the regulation of cell proliferation. They propose that NDP is a molecule related in function to these genes and may be involved in a pathway that regulates neural cell differentiation and proliferation. 19 refs., 2 figs.

Chen, Z.Y.; Battinelli, E.M.; Hendriks, R.W.; Craig, I.W. [Univ. of Oxford (United Kingdom); Powell, J.F. [Institute of Psychiatry, London (United Kingdom); Middleton-Price, H. [Univ. of London (United Kingdom); Sims, K.B.; Breakefield, X.O. [Massachusetts General Hospital, Charlestown, MA (United States)

1993-05-01

135

A global view of pleiotropy and phenotypically derived gene function in yeast  

Microsoft Academic Search

Pleiotropy, the ability of a single mutant gene to cause multiple mutant phenotypes, is a relatively common but poorly understood phenomenon in biology. Perhaps the greatest challenge in the analysis of pleiotropic genes is determining whether phenotypes associated with a mutation result from the loss of a single function or of multiple functions encoded by the same gene. Here we

Aimée Marie Dudley; Daniel Maarten Janse; Amos Tanay; Ron Shamir; George McDonald Church

2005-01-01

136

Action comprehension: deriving spatial and functional relations.  

PubMed

A perceived action can be understood only when information about the action carried out and the objects used are taken into account. It was investigated how spatial and functional information contributes to establishing these relations. Participants observed static frames showing a hand wielding an instrument and a potential target object of the action. The 2 elements could either match or mismatch, spatially or functionally. Participants were required to judge only 1 of the 2 relations while ignoring the other. Both irrelevant spatial and functional mismatches affected judgments of the relevant relation. Moreover, the functional relation provided a context for the judgment of the spatial relation but not vice versa. The results are discussed in respect to recent accounts of action understanding. PMID:15982126

Bach, Patric; Knoblich, Günther; Gunter, Thomas C; Friederici, Angela D; Prinz, Wolfgang

2005-06-01

137

Cellular functions of genetically imprinted genes in human and mouse as annotated in the gene ontology.  

PubMed

By analyzing the cellular functions of genetically imprinted genes as annotated in the Gene Ontology for human and mouse, we found that imprinted genes are often involved in developmental, transport and regulatory processes. In the human, paternally expressed genes are enriched in GO terms related to the development of organs and of anatomical structures. In the mouse, maternally expressed genes regulate cation transport as well as G-protein signaling processes. Furthermore, we investigated if imprinted genes are regulated by common transcription factors. We identified 25 TF families that showed an enrichment of binding sites in the set of imprinted genes in human and 40 TF families in mouse. In general, maternally and paternally expressed genes are not regulated by different transcription factors. The genes Nnat, Klf14, Blcap, Gnas and Ube3a contribute most to the enrichment of TF families. In the mouse, genes that are maternally expressed in placenta are enriched for AP1 binding sites. In the human, we found that these genes possessed binding sites for both, AP1 and SP1. PMID:23226257

Hamed, Mohamed; Ismael, Siba; Paulsen, Martina; Helms, Volkhard

2012-11-30

138

Cellular Functions of Genetically Imprinted Genes in Human and Mouse as Annotated in the Gene Ontology  

PubMed Central

By analyzing the cellular functions of genetically imprinted genes as annotated in the Gene Ontology for human and mouse, we found that imprinted genes are often involved in developmental, transport and regulatory processes. In the human, paternally expressed genes are enriched in GO terms related to the development of organs and of anatomical structures. In the mouse, maternally expressed genes regulate cation transport as well as G-protein signaling processes. Furthermore, we investigated if imprinted genes are regulated by common transcription factors. We identified 25 TF families that showed an enrichment of binding sites in the set of imprinted genes in human and 40 TF families in mouse. In general, maternally and paternally expressed genes are not regulated by different transcription factors. The genes Nnat, Klf14, Blcap, Gnas and Ube3a contribute most to the enrichment of TF families. In the mouse, genes that are maternally expressed in placenta are enriched for AP1 binding sites. In the human, we found that these genes possessed binding sites for both, AP1 and SP1.

Hamed, Mohamed; Ismael, Siba; Paulsen, Martina; Helms, Volkhard

2012-01-01

139

Age-Related Changes in Task Related Functional Network Connectivity  

PubMed Central

Aging has a multi-faceted impact on brain structure, brain function and cognitive task performance, but the interaction of these different age-related changes is largely unexplored. We hypothesize that age-related structural changes alter the functional connectivity within the brain, resulting in altered task performance during cognitive challenges. In this neuroimaging study, we used independent components analysis to identify spatial patterns of coordinated functional activity involved in the performance of a verbal delayed item recognition task from 75 healthy young and 37 healthy old adults. Strength of functional connectivity between spatial components was assessed for age group differences and related to speeded task performance. We then assessed whether age-related differences in global brain volume were associated with age-related differences in functional network connectivity. Both age groups used a series of spatial components during the verbal working memory task and the strength and distribution of functional network connectivity between these components differed across the age groups. Poorer task performance, i.e. slower speed with increasing memory load, in the old adults was associated with decreases in functional network connectivity between components comprised of the supplementary motor area and the middle cingulate and between the precuneus and the middle/superior frontal cortex. Advancing age also led to decreased brain volume; however, there was no evidence to support the hypothesis that age-related alterations in functional network connectivity were the result of global brain volume changes. These results suggest that age-related differences in the coordination of neural activity between brain regions partially underlie differences in cognitive performance.

Steffener, Jason; Habeck, Christian G.; Stern, Yaakov

2012-01-01

140

A widespread class of reverse transcriptase-related cellular genes  

PubMed Central

Reverse transcriptases (RTs) polymerize DNA on RNA templates. They fall into several structurally related but distinct classes and form an assemblage of RT-like enzymes that, in addition to RTs, also includes certain viral RNA-dependent RNA polymerases (RdRP) synthesizing RNA on RNA templates. It is generally believed that most RT-like enzymes originate from retrotransposons or viruses and have no specific function in the host cell, with telomerases being the only notable exception. Here we report on the discovery and properties of a unique class of RT-related cellular genes collectively named rvt. We present evidence that rvts are not components of retrotransposons or viruses, but single-copy genes with a characteristic domain structure that may contain introns in evolutionarily conserved positions, occur in syntenic regions, and evolve under purifying selection. These genes can be found in all major taxonomic groups including protists, fungi, animals, plants, and even bacteria, although they exhibit patchy phylogenetic distribution in each kingdom. We also show that the RVT protein purified from one of its natural hosts, Neurospora crassa, exists in a multimeric form and has the ability to polymerize NTPs as well as dNTPs in vitro, with a strong preference for NTPs, using Mn2+ as a cofactor. The existence of a previously unknown class of single-copy RT-related genes calls for reevaluation of the current views on evolution and functional roles of RNA-dependent polymerases in living cells.

Gladyshev, Eugene A.; Arkhipova, Irina R.

2011-01-01

141

Pathogenesis-related proteins and their genes in cereals  

Microsoft Academic Search

Pathogenesis-related proteins (PR-proteins) are induced in plants in response to attack by microbial or insect pests. They\\u000a have been classified into several groups (PR-1 through PR-14 at present) based on their amino acid sequences and biochemical\\u000a functions. Many of these proteins that have been purified from infected plants or seed extracts possess antifungal or insecticidal\\u000a activity. Genes and cDNA clones

S. Muthukrishnan; George H. Liang; Harold N. Trick; Bikram S. Gill

2001-01-01

142

Relating equivalence relations to equivalence relations: A relational framing model of complex human functioning  

PubMed Central

The current study aimed to develop a behavior-analytic model of analogical reasoning. In Experiments 1 and 2 subjects (adults and children) were trained and tested for the formation of four, three-member equivalence relations using a delayed matching-to-sample procedure. All subjects (Experiments 1 and 2) were exposed to tests that examined relations between equivalence and non-equivalence relations. For example, on an equivalence-equivalence relation test, the complex sample B1/C1 and the two complex comparisons B3/C3 and B3/C4 were used, and on a nonequivalence-nonequivalence relation test the complex sample B1/C2 was presented with the same two comparisons. All subjects consistently related equivalence relations to equivalence relations and nonequivalence relations to nonequivalence relations (e.g., picked B3/C3 in the presence of B1/C1 and picked B3/C4 in the presence of B1/C2). In Experiment 3, the equivalence responding, the equivalence-equivalence responding, and the nonequivalence-nonequivalence responding was successfully brought under contextual control. Finally, it was shown that the contextual cues could function successfully as comparisons, and the complex samples and comparisons could function successfully as contextual cues and samples, respectively. These data extend the equivalence paradigm and contribute to a behaviour-analytic interpretation of analogical reasoning and complex human functioning, in general.

Barnes, Dermot; Hegarty, Neil; Smeets, Paul M.

1997-01-01

143

Polyploidization altered gene functions in cotton (Gossypium spp.).  

PubMed

Cotton (Gossypium spp.) is an important crop plant that is widely grown to produce both natural textile fibers and cottonseed oil. Cotton fibers, the economically more important product of the cotton plant, are seed trichomes derived from individual cells of the epidermal layer of the seed coat. It has been known for a long time that large numbers of genes determine the development of cotton fiber, and more recently it has been determined that these genes are distributed across At and Dt subgenomes of tetraploid AD cottons. In the present study, the organization and evolution of the fiber development genes were investigated through the construction of an integrated genetic and physical map of fiber development genes whose functions have been verified and confirmed. A total of 535 cotton fiber development genes, including 103 fiber transcription factors, 259 fiber development genes, and 173 SSR-contained fiber ESTs, were analyzed at the subgenome level. A total of 499 fiber related contigs were selected and assembled. Together these contigs covered about 151 Mb in physical length, or about 6.7% of the tetraploid cotton genome. Among the 499 contigs, 397 were anchored onto individual chromosomes. Results from our studies on the distribution patterns of the fiber development genes and transcription factors between the At and Dt subgenomes showed that more transcription factors were from Dt subgenome than At, whereas more fiber development genes were from At subgenome than Dt. Combining our mapping results with previous reports that more fiber QTLs were mapped in Dt subgenome than At subgenome, the results suggested a new functional hypothesis for tetraploid cotton. After the merging of the two diploid Gossypium genomes, the At subgenome has provided most of the genes for fiber development, because it continues to function similar to its fiber producing diploid A genome ancestor. On the other hand, the Dt subgenome, with its non-fiber producing D genome ancestor, provides more transcription factors that regulate the expression of the fiber genes in the At subgenome. This hypothesis would explain previously published mapping results. At the same time, this integrated map of fiber development genes would provide a framework to clone individual full-length fiber genes, to elucidate the physiological mechanisms of the fiber differentiation, elongation, and maturation, and to systematically study the functional network of these genes that interact during the process of fiber development in the tetraploid cottons. PMID:21179551

Xu, Zhanyou; Yu, John Z; Cho, Jaemin; Yu, Jing; Kohel, Russell J; Percy, Richard G

2010-12-16

144

Functional Status After Childbirth and Related Concepts  

Microsoft Academic Search

The purpose of this study was to explore relationships between functional status after childbirth and related concepts. The sample consisted of 177 women. The Personal Resource Questionnaire (PRQ) 85—Part 2, the State Trait Anxiety Inventory (STAI), and the Inventory of Functional Status After Childbirth (IFSAC) were used to measure variables. Data were collected during the third trimester of pregnancy and

Nadine M. Aktan

2010-01-01

145

X gene-related sequences in the core gene of duck and heron hepatitis B viruses.  

PubMed Central

The genomes of all known mammalian hepadnaviruses contain an open reading frame (ORF), designated X, located just upstream from the gene encoding the major viral nucleocapsid polypeptide. This gene is believed to have one or more roles central to the life cycle of these viruses. Consequently, it is surprising that avian hepadnaviruses appear to lack this ORF. However, the observation that the size and position of the core gene in the duck hepatitis B virus (DHBV) genome and the heron hepatitis B virus (HHBV) genome is comparable to the combined X and core genes of the mammalian hepadnaviruses suggests that X function(s) may be performed by the major nucleocapsid polypeptide of DHBV and HHBV. Computer-assisted analyses were carried out to test the hypothesis that the primary and secondary structural characteristics of the X gene product are also present in the major core gene product of the duck (DHBcAg) and heron (HHBcAg) viruses. Primary sequence comparison of the major core-associated polypeptides encoded by the avian and mammalian hepadnaviruses demonstrates considerable homology at both the amino- and carboxyl-terminal regions of these components. However, the middle portion of the DHBcAg and HHBcAg polypeptide, spanning about half the molecule, is unique. Comparison of this region with the carboxyl-terminal half of the X gene sequences from mammalian hepadnaviruses demonstrates similarities in both primary sequence and secondary structural characteristics. These results suggest that X-like gene product sequences are present in the core gene products of DHBV and HHBV. In addition, a sequence of about two dozen residues at the amino terminus of the mammalian X gene product, overlapping the polymerase gene product, is found in the corresponding position in DHBV. This is consistent with the conclusion that the relationship between the DHBV and HHBV core genes compared to the X and core genes of the mammalian hepadnaviruses may be explained by one or more translocations in the this region of the viral genome. The previous finding of X antigen determinants associated with one or more core-related polypeptides in the mammalian hepadnaviruses, combined with the results of this study, suggests that X gene product function is conserved among these viruses.

Feitelson, M A; Miller, R H

1988-01-01

146

Inferring gene transcriptional modulatory relations: a genetical genomics approach  

SciTech Connect

Bayesian network modeling is a promising approach to define and evaluate gene expression circuits in diverse tissues and cell types under different experimental conditions. The power and practicality of this approach can be improved by restricting the number of potential interactions among genes and by defining causal relations before evaluating posterior probabilities for billions of networks. A newly developed genetical genomics method that combines transcriptome profiling with complex trait analysis now provides strong constraints on network architecture. This method detects those chromosomal intervals responsible for differences in mRNA expression using quantitative trait locus (QTL) mapping. We have developed an efficient Bayesian approach that exploits the genetical genomics method to focus computational effort on the most plausible gene modulatory networks. We exploit a dense marker map for a genetic reference population (GRP) that consists of 32 BXD strains of mice made by intercrossing two progenitor strains- C57BL/6J and DBA/2J. These progenitors differ at 1.3 million known single nucleotide polymorphisms (SNPs), all of which can be exploited to estimate the probability that a gene contains functional polymorphisms that segregate within the GRP. We constructed 66 candidate networks that include all the candidate modulator genes located in the 209 statistically significant trans-acting QTL regions. SNPs that distinguish between the two progenitor strains were used to further winnow the list of candidate modulators. Bayesian network was then used to identify the genetic modulatory relations that best explain the microarray data.

Li, Hongqiang [University of Tennessee Health Science Center, Memphis; Lu, Lu [University of Tennessee Health Science Center, Memphis; Manly, Kenneth [University of Tennessee Health Science Center, Memphis; Chesler, Elissa J [ORNL; Bao, Lei [University of Tennessee Health Science Center, Memphis; Wang, Jintao [University of Tennessee Health Science Center, Memphis; Zhou, Mi [University of Tennessee Health Science Center, Memphis; Williams, Robert [University of Tennessee Health Science Center, Memphis; Cui, Yan [University of Tennessee Health Science Center, Memphis

2005-01-01

147

Gene expression in placentation of farm animals: an overview of gene function during development.  

PubMed

Eutherian mammals share a common ancestor that evolved into two main placental types, i.e., hemotrophic (e.g., human and mouse) and histiotrophic (e.g., farm animals), which differ in invasiveness. Pregnancies initiated with assisted reproductive techniques (ART) in farm animals are at increased risk of failure; these losses were associated with placental defects, perhaps due to altered gene expression. Developmentally regulated genes in the placenta seem highly phylogenetically conserved, whereas those expressed later in pregnancy are more species-specific. To elucidate differences between hemotrophic and epitheliochorial placentae, gene expression data were compiled from microarray studies of bovine placental tissues at various stages of pregnancy. Moreover, an in silico subtractive library was constructed based on homology of bovine genes to the database of zebrafish - a nonplacental vertebrate. In addition, the list of placental preferentially expressed genes for the human and mouse were collected using bioinformatics tools (Tissue-specific Gene Expression and Regulation [TiGER] - for humans, and tissue-specific genes database (TiSGeD) - for mice and humans). Humans, mice, and cattle shared 93 genes expressed in their placentae. Most of these were related to immune function (based on analysis of gene ontology). Cattle and women shared expression of 23 genes, mostly related to hormonal activity, whereas mice and women shared 16 genes (primarily sexual differentiation and glycoprotein biology). Because the number of genes expressed by the placentae of both cattle and mice were similar (based on cluster analysis), we concluded that both cattle and mice were suitable models to study the biology of the human placenta. PMID:21550103

Barreto, R S N; Bressan, F F; Oliveira, L J; Pereira, F T V; Perecin, F; Ambrósio, C E; Meirelles, F V; Miglino, M A

2011-05-07

148

A weighted power framework for integrating multisource information: gene function prediction in yeast.  

PubMed

Predicting the functions of unannotated genes is one of the major challenges of biological investigation. In this study, we propose a weighted power scoring framework, called weighted power biological score (WPBS), for combining different biological data sources and predicting the function of some of the unclassified yeast Saccharomyces cerevisiae genes. The relative power and weight coefficients of different data sources, in the proposed score, are estimated systematically by utilizing functional annotations [yeast Gene Ontology (GO)-Slim: Process] of classified genes, available from Saccharomyces Genome Database. Genes are then clustered by applying k-medoids algorithm on WPBS, and functional categories of 334 unclassified genes are predicted using a P-value cutoff 1 ×10(-5). The WPBS is available online at http://www.isical.ac.in/~ shubhra/WPBS/WPBS.html, where one can download WPBS, related files, and a MATLAB code to predict functions of unclassified genes. PMID:22318478

Ray, Shubhra Sankar; Bandyopadhyay, Sanghamitra; Pal, Sankar K

2012-02-03

149

Rabbit calcium-sensing receptor (CASR) gene: chromosome location and evidence for related genes.  

PubMed

Diverse cellular functions are regulated by the calcium-sensing receptor, encoded by the CASR gene, which plays an important role in calcium homeostasis. Here we provide the sequence for exon VII of the rabbit CASR gene and show that it is 91% identical to the human gene at the nucleotide level, and 95% identical at the amino acid level. The gene was mapped by fluorescence in situ hybridization, using a cosmid isolated from a genomic library, to chromosome 14q11 and this was confirmed independently by PCR amplification of flow sorted chromosomes. In addition, the cosmid detected sites with lower frequencies on four other chromosomes: 3q, 5p, 8p, and 13p. Two of these sites (5p and 13p) were also detected by a related but unidentical cosmid, and map to regions that are homologous to the mouse calcium-sensing receptor related sequences (Casr-rs); suggesting that they may represent CASR-related sequences in the rabbit. The data support the presence of a family of genes related to the calcium-sensing receptor in the G-protein coupled receptor (GPCR) superfamily, as well as extend the existing knowledge of homology for several human and rabbit chromosomes. PMID:10575221

Martin-DeLeon, P A; Canaff, L; Korstanje, R; Bhide, V; Selkirk, M; Hendy, G N

1999-01-01

150

Gene Profiling of Mta1 Identifies Novel Gene Targets and Functions  

PubMed Central

Background Metastasis-associated protein 1 (MTA1), a master dual co-regulatory protein is found to be an integral part of NuRD (Nucleosome Remodeling and Histone Deacetylation) complex, which has indispensable transcriptional regulatory functions via histone deacetylation and chromatin remodeling. Emerging literature establishes MTA1 to be a valid DNA-damage responsive protein with a significant role in maintaining the optimum DNA-repair activity in mammalian cells exposed to genotoxic stress. This DNA-damage responsive function of MTA1 was reported to be a P53-dependent and independent function. Here, we investigate the influence of P53 on gene regulation function of Mta1 to identify novel gene targets and functions of Mta1. Methods Gene expression analysis was performed on five different mouse embryonic fibroblasts (MEFs) samples (i) the Mta1 wild type, (ii) Mta1 knock out (iii) Mta1 knock out in which Mta1 was reintroduced (iv) P53 knock out (v) P53 knock out in which Mta1 was over expressed using Affymetrix Mouse Exon 1.0 ST arrays. Further Hierarchical Clustering, Gene Ontology analysis with GO terms satisfying corrected p-value<0.1, and the Ingenuity Pathway Analysis were performed. Finally, RT-qPCR was carried out on selective candidate genes. Significance/Conclusion This study represents a complete genome wide screen for possible target genes of a coregulator, Mta1. The comparative gene profiling of Mta1 wild type, Mta1 knockout and Mta1 re-expression in the Mta1 knockout conditions define “bona fide” Mta1 target genes. Further extensive analyses of the data highlights the influence of P53 on Mta1 gene regulation. In the presence of P53 majority of the genes regulated by Mta1 are related to inflammatory and anti-microbial responses whereas in the absence of P53 the predominant target genes are involved in cancer signaling. Thus, the presented data emphasizes the known functions of Mta1 and serves as a rich resource which could help us identify novel Mta1 functions.

Eswaran, Jeyanthy; Kumar, Rakesh

2011-01-01

151

Bacterial community assembly based on functional genes rather than species  

PubMed Central

The principles underlying the assembly and structure of complex microbial communities are an issue of long-standing concern to the field of microbial ecology. We previously analyzed the community membership of bacterial communities associated with the green macroalga Ulva australis, and proposed a competitive lottery model for colonization of the algal surface in an attempt to explain the surprising lack of similarity in species composition across different algal samples. Here we extend the previous study by investigating the link between community structure and function in these communities, using metagenomic sequence analysis. Despite the high phylogenetic variability in microbial species composition on different U. australis (only 15% similarity between samples), similarity in functional composition was high (70%), and a core of functional genes present across all algal-associated communities was identified that were consistent with the ecology of surface- and host-associated bacteria. These functions were distributed widely across a variety of taxa or phylogenetic groups. This observation of similarity in habitat (niche) use with respect to functional genes, but not species, together with the relative ease with which bacteria share genetic material, suggests that the key level at which to address the assembly and structure of bacterial communities may not be “species” (by means of rRNA taxonomy), but rather the more functional level of genes.

Burke, Catherine; Steinberg, Peter; Rusch, Doug; Kjelleberg, Staffan; Thomas, Torsten

2011-01-01

152

Maladaptive functional relations in client verbal behavior  

PubMed Central

Skinner's analysis of verbal behavior is applied in this paper to several kinds of maladaptive behavior with which clinicians must deal. Lying, denial, and poor observing skills are discussed as defective tacting repertoires. Demanding and manipulative behaviors are mands that obtain immediate reinforcement at the expense of disrupting long-term interpersonal relations. Obsessing is runaway intraverbal behavior. Variables that enter into the maladaptive functional relations are examined.

Glenn, Sigrid S.

1983-01-01

153

DNase II: genes, enzymes and function  

Microsoft Academic Search

Deoxyribonuclease (DNase) II, which was discovered more than 50 years ago, is a mammalian endonuclease that functions optimally at acid pH in the absence of divalent cations. Its lysosomal localization and ubiquitous tissue distribution suggested that this enzyme played a role in the degradation of exogenous DNA encountered by phagocytosis, although the relative importance of such a role was unknown.

Cory J. Evans; Renato J. Aguilera

2003-01-01

154

Executive Functioning and Alcohol-Related Aggression  

Microsoft Academic Search

The primary goal of this investigation was to determine whether executive functioning (EF) would moderate the alcohol-aggression relation. Participants were 310 (152 men and 158 women) healthy social drinkers between 21 and 35 years of age. EF as well as non-EF skills were measured with 13 validated neuropsychological tests. Following the consumption of either an alcoholic or a placebo beverage,

Peter R. Giancola

2004-01-01

155

Horizontal gene transfer of microbial cellulases into nematode genomes is associated with functional assimilation and gene turnover  

PubMed Central

Background Natural acquisition of novel genes from other organisms by horizontal or lateral gene transfer is well established for microorganisms. There is now growing evidence that horizontal gene transfer also plays important roles in the evolution of eukaryotes. Genome-sequencing and EST projects of plant and animal associated nematodes such as Brugia, Meloidogyne, Bursaphelenchus and Pristionchus indicate horizontal gene transfer as a key adaptation towards parasitism and pathogenicity. However, little is known about the functional activity and evolutionary longevity of genes acquired by horizontal gene transfer and the mechanisms favoring such processes. Results We examine the transfer of cellulase genes to the free-living and beetle-associated nematode Pristionchus pacificus, for which detailed phylogenetic knowledge is available, to address predictions by evolutionary theory for successful gene transfer. We used transcriptomics in seven Pristionchus species and three other related diplogastrid nematodes with a well-defined phylogenetic framework to study the evolution of ancestral cellulase genes acquired by horizontal gene transfer. We performed intra-species, inter-species and inter-genic analysis by comparing the transcriptomes of these ten species and tested for cellulase activity in each species. Species with cellulase genes in their transcriptome always exhibited cellulase activity indicating functional integration into the host's genome and biology. The phylogenetic profile of cellulase genes was congruent with the species phylogeny demonstrating gene longevity. Cellulase genes show notable turnover with elevated birth and death rates. Comparison by sequencing of three selected cellulase genes in 24 natural isolates of Pristionchus pacificus suggests these high evolutionary dynamics to be associated with copy number variations and positive selection. Conclusion We could demonstrate functional integration of acquired cellulase genes into the nematode's biology as predicted by theory. Thus, functional assimilation, remarkable gene turnover and selection might represent key features of horizontal gene transfer events in nematodes.

2011-01-01

156

Caspase Gene Expression in the Brain as a Function of the Clinical Progression of Alzheimer Disease  

Microsoft Academic Search

Background: Caspase gene expression has previously been reported in terminal Alzheimer disease (AD) brain, but, currently, little is known about the temporal pat- tern of caspase gene expression relative to the onset and clinical progression of AD. Objective: To derive a profile of caspase gene expres- sion and proapoptotic indexes as a function of the clinical and neuropathologic progression of

Patrick N. Pompl; Shrishailam Yemul; Zhongmin Xiang; Lap Ho; Varham Haroutunian; Dushyant Purohit; Richard Mohs; Giulio Maria Pasinetti

2003-01-01

157

A guide to the Lhc genes and their relatives in Arabidopsis  

Microsoft Academic Search

The Lhc super-gene family encodes the light-harvesting chlorophyll a\\/b-binding (LHC) proteins that constitute the antenna system of the photosynthetic apparatus, and also includes some relatives whose functions are more or less unknown. The Lhc super-gene family of Arabidopsis contains >30 members and the databases contain >1000 EST clones originating from these genes. This article presents an overview of these genes

Stefan Jansson

1999-01-01

158

Gain of Function Mutations for Paralogous Hox Genes: Implications for the Evolution of Hox Gene Function  

Microsoft Academic Search

To investigate the functions of paralogous Hox genes, we compared the phenotypic consequences of altering the embryonic patterns of expression of Hoxb-8 and Hoxc-8 in transgenic mice. A comparison of the phenotypic consequences of altered expression of the two paralogs in the axial skeletons of newborns revealed an array of common transformations as well as morphological changes unique to each

Robert A. Pollock; Taduru Sreenath; Lien Ngo; Charles J. Bieberich

1995-01-01

159

A subset of metzincins and related genes constitutes a marker of human solid organ fibrosis  

Microsoft Academic Search

Metzincins and functionally related genes play important roles in extracellular matrix remodeling both in healthy and fibrotic\\u000a conditions. We recently presented a transcriptomic classifier consisting of 19 metzincins and related genes (MARGS) discriminating\\u000a biopsies from renal transplant patients with or without interstitial fibrosis\\/tubular atrophy (IF\\/TA) by virtue of gene expression\\u000a measurement (Roedder et al., Am J Transplant 9:517–526, 2009). Here

Silke Rödder; Andreas Scherer; Meike Körner; Hans-Peter Marti

2011-01-01

160

A family of genes related to a new expression site-associated gene in Trypanosoma equiperdum.  

PubMed Central

Two genes, belonging to a new expression site-associated gene family of six to eight members in Trypanosoma equiperdum and Trypanosoma brucei, have been cloned from a T. equiperdum variant. One of them, called ESAG-9c, is contained in the 1.78-C expression site and is found just upstream of the 5' barren region. The other one, called ESAG-9u, is unique in the family, is not telomere linked, and apparently is not expression site related. A 2-kb poly(A)+ mRNA is detected with probes for this ESAG-9 family in all T. equiperdum variants examined. By using polymerase chain reaction and restriction fragment length polymorphism techniques, it has been possible to distinguish between ESAG-9c and ESAG-9u and to show that ESAG-9c is transcribed in an expression site-specific manner. However, ESAG-9u (or another gene in the family having identical characteristics) is transcribed in all variants, regardless of the expression site used by these variants. Thus, this ESAG-9 family contains at least one gene that is under expression site control but might have other genes that are not. The function of these ESAG-9 genes is unknown. Transcripts homologous to ESAG-9 were detected in T. brucei bloodstream forms but not in procyclics. Images

Florent, I C; Raibaud, A; Eisen, H

1991-01-01

161

Bacterial genes in the aphid genome: absence of functional gene transfer from Buchnera to its host.  

PubMed

Genome reduction is typical of obligate symbionts. In cellular organelles, this reduction partly reflects transfer of ancestral bacterial genes to the host genome, but little is known about gene transfer in other obligate symbioses. Aphids harbor anciently acquired obligate mutualists, Buchnera aphidicola (Gammaproteobacteria), which have highly reduced genomes (420-650 kb), raising the possibility of gene transfer from ancestral Buchnera to the aphid genome. In addition, aphids often harbor other bacteria that also are potential sources of transferred genes. Previous limited sampling of genes expressed in bacteriocytes, the specialized cells that harbor Buchnera, revealed that aphids acquired at least two genes from bacteria. The newly sequenced genome of the pea aphid, Acyrthosiphon pisum, presents the first opportunity for a complete inventory of genes transferred from bacteria to the host genome in the context of an ancient obligate symbiosis. Computational screening of the entire A. pisum genome, followed by phylogenetic and experimental analyses, provided strong support for the transfer of 12 genes or gene fragments from bacteria to the aphid genome: three LD-carboxypeptidases (LdcA1, LdcA2,psiLdcA), five rare lipoprotein As (RlpA1-5), N-acetylmuramoyl-L-alanine amidase (AmiD), 1,4-beta-N-acetylmuramidase (bLys), DNA polymerase III alpha chain (psiDnaE), and ATP synthase delta chain (psiAtpH). Buchnera was the apparent source of two highly truncated pseudogenes (psiDnaE and psiAtpH). Most other transferred genes were closely related to genes from relatives of Wolbachia (Alphaproteobacteria). At least eight of the transferred genes (LdcA1, AmiD, RlpA1-5, bLys) appear to be functional, and expression of seven (LdcA1, AmiD, RlpA1-5) are highly upregulated in bacteriocytes. The LdcAs and RlpAs appear to have been duplicated after transfer. Our results excluded the hypothesis that genome reduction in Buchnera has been accompanied by gene transfer to the host nuclear genome, but suggest that aphids utilize a set of duplicated genes acquired from other bacteria in the context of the Buchnera-aphid mutualism. PMID:20195500

Nikoh, Naruo; McCutcheon, John P; Kudo, Toshiaki; Miyagishima, Shin-ya; Moran, Nancy A; Nakabachi, Atsushi

2010-02-26

162

Bacterial Genes in the Aphid Genome: Absence of Functional Gene Transfer from Buchnera to Its Host  

PubMed Central

Genome reduction is typical of obligate symbionts. In cellular organelles, this reduction partly reflects transfer of ancestral bacterial genes to the host genome, but little is known about gene transfer in other obligate symbioses. Aphids harbor anciently acquired obligate mutualists, Buchnera aphidicola (Gammaproteobacteria), which have highly reduced genomes (420–650 kb), raising the possibility of gene transfer from ancestral Buchnera to the aphid genome. In addition, aphids often harbor other bacteria that also are potential sources of transferred genes. Previous limited sampling of genes expressed in bacteriocytes, the specialized cells that harbor Buchnera, revealed that aphids acquired at least two genes from bacteria. The newly sequenced genome of the pea aphid, Acyrthosiphon pisum, presents the first opportunity for a complete inventory of genes transferred from bacteria to the host genome in the context of an ancient obligate symbiosis. Computational screening of the entire A. pisum genome, followed by phylogenetic and experimental analyses, provided strong support for the transfer of 12 genes or gene fragments from bacteria to the aphid genome: three LD–carboxypeptidases (LdcA1, LdcA2,?LdcA), five rare lipoprotein As (RlpA1-5), N-acetylmuramoyl-L-alanine amidase (AmiD), 1,4-beta-N-acetylmuramidase (bLys), DNA polymerase III alpha chain (?DnaE), and ATP synthase delta chain (?AtpH). Buchnera was the apparent source of two highly truncated pseudogenes (?DnaE and ?AtpH). Most other transferred genes were closely related to genes from relatives of Wolbachia (Alphaproteobacteria). At least eight of the transferred genes (LdcA1, AmiD, RlpA1-5, bLys) appear to be functional, and expression of seven (LdcA1, AmiD, RlpA1-5) are highly upregulated in bacteriocytes. The LdcAs and RlpAs appear to have been duplicated after transfer. Our results excluded the hypothesis that genome reduction in Buchnera has been accompanied by gene transfer to the host nuclear genome, but suggest that aphids utilize a set of duplicated genes acquired from other bacteria in the context of the Buchnera–aphid mutualism.

Nikoh, Naruo; McCutcheon, John P.; Kudo, Toshiaki; Miyagishima, Shin-ya; Moran, Nancy A.; Nakabachi, Atsushi

2010-01-01

163

Structure-function evolution of the Transforming acidic coiled coil genes revealed by analysis of phylogenetically diverse organisms  

Microsoft Academic Search

BACKGROUND: Examination of ancient gene families can provide an insight into how the evolution of gene structure can relate to function. Functional homologs of the evolutionarily conserved transforming acidic coiled coil (TACC) gene family are present in organisms from yeast to man. However, correlations between functional interactions and the evolution of these proteins have yet to be determined. RESULTS: We

Ivan H Still; Ananthalakshmy K Vettaikkorumakankauv; Anthony DiMatteo; Ping Liang

2004-01-01

164

Implication of synapse-related genes in bipolar disorder by linkage and gene expression analyses  

PubMed Central

Several chromosomal regions have been linked to bipolar disorder (BD). However, the search for specific genes has been hampered by inconsistent findings, partly due to genetic and phenotypic heterogeneity. We focused on lithium-responsive bipolar patients, a subgroup thought to be more homogeneous and conducted a multistage study including an initial linkage study followed up by fine mapping and gene expression. Our sample consisted of 36 families (275 genotyped individuals, 132 affected) recruited through probands who were responders to long-term lithium treatment. We conducted a genome-wide scan with 811 microsatellite markers followed by fine mapping. Gene expression studies of candidate regions were conducted on six post-mortem prefrontal brain regions of 20 individuals (8 BD and 12 controls). We identified regions 3p25, 3p14 and 14q11 as showing the highest genome-wide linkage signal (LOD 2.53, 2.04 and 3.19, respectively). Fine mapping provided further support for 3p25, while only modest support was found in the other two regions. We identified a group of synaptic, mitochondrial and apoptotic genes with altered expression patterns in BD. Analysis of an independent microarray dataset supported the implication of synapse-related and mitochondrial genes in BD. In conclusion, using two complementary strategies, we found evidence of linkage to lithium-responsive BD on 3p25, 3p14 and 14q11 as well as significantly dysregulated genes on these regions suggesting altered synaptic and mitochondrial function in BD. Further studies are warranted to demonstrate the functional role of these genes in BD.

de Lara, Catalina Lopez; Jaitovich-Groisman, Iris; Cruceanu, Cristiana; Mamdani, Firoza; Lebel, Veronique; Yerko, Volodymyr; Beck, Angus; Young, L. Trevor; Rouleau, Guy; Grof, Paul; Alda, Martin; Turecki, Gustavo

2012-01-01

165

Functional overlap between the mec-8 gene and five sym genes in Caenorhabditis elegans.  

PubMed Central

Earlier work showed that the Caenorhabditis elegans gene mec-8 encodes a regulator of alternative RNA splicing and that mec-8 null mutants have defects in sensory neurons and body muscle attachment but are generally viable and fertile. We have used a genetic screen to identify five mutations in four genes, sym-1-sym-4, that are synthetically lethal with mec-8 loss-of-function mutations. The phenotypes of sym single mutants are essentially wild type. mec-8; sym-1 embryos arrest during embryonic elongation and exhibit defects in the attachment of body muscle to extracellular cuticle. sym-1 can encode a protein containing a signal sequence and 15 contiguous leucine-rich repeats. A fusion of sym-1 and the gene for green fluorescent protein rescued the synthetic lethality of mec-8; sym-1 mutants; the fusion protein was secreted from the apical hypodermal surface of the embryo. We propose that SYM-1 helps to attach body muscle to the extracellular cuticle and that another gene that is dependent upon mec-8 for pre-mRNA processing overlaps functionally with sym-1. RNA-mediated interference experiments indicated that a close relative of sym-1 functionally overlaps both sym-1 and mec-8 in affecting muscle attachment. sym-2, sym-3, and sym-4 appear to provide additional functions that are essential in the absence of mec-8(+).

Davies, A G; Spike, C A; Shaw, J E; Herman, R K

1999-01-01

166

Gene function prediction based on genomic context clustering and discriminative learning: an application to bacteriophages  

PubMed Central

Background Existing methods for whole-genome comparisons require prior knowledge of related species and provide little automation in the function prediction process. Bacteriophage genomes are an example that cannot be easily analyzed by these methods. This work addresses these shortcomings and aims to provide an automated prediction system of gene function. Results We have developed a novel system called SynFPS to perform gene function prediction over completed genomes. The prediction system is initialized by clustering a large collection of weakly related genomes into groups based on their resemblance in gene distribution. From each individual group, data are then extracted and used to train a Support Vector Machine that makes gene function predictions. Experiments were conducted with 9 different gene functions over 296 bacteriophage genomes. Cross validation results gave an average prediction accuracy of ~80%, which is comparable to other genomic-context based prediction methods. Functional predictions are also made on 3 uncharacterized genes and 12 genes that cannot be identified by sequence alignment. The software is publicly available at . Conclusion The proposed system employs genomic context to predict gene function and detect gene correspondence in whole-genome comparisons. Although our experimental focus is on bacteriophages, the method may be extended to other microbial genomes as they share a number of similar characteristics with phage genomes such as gene order conservation.

Li, Jason; Halgamuge, Saman K; Kells, Christopher I; Tang, Sen-Lin

2007-01-01

167

Age-related regulation of genes: slow homeostatic changes and age-dimension technology  

NASA Astrophysics Data System (ADS)

Through systematic studies of pro- and anti-blood coagulation factors, we have determined molecular mechanisms involving two genetic elements, age-related stability element (ASE), GAGGAAG and age-related increase element (AIE), a unique stretch of dinucleotide repeats (AIE). ASE and AIE are essential for age-related patterns of stable and increased gene expression patterns, respectively. Such age-related gene regulatory mechanisms are also critical for explaining homeostasis in various physiological reactions as well as slow homeostatic changes in them. The age-related increase expression of the human factor IX (hFIX) gene requires the presence of both ASE and AIE, which apparently function additively. The anti-coagulant factor protein C (hPC) gene uses an ASE (CAGGAG) to produce age-related stable expression. Both ASE sequences (G/CAGAAG) share consensus sequence of the transcriptional factor PEA-3 element. No other similar sequences, including another PEA-3 consensus sequence, GAGGATG, function in conferring age-related gene regulation. The age-regulatory mechanisms involving ASE and AIE apparently function universally with different genes and across different animal species. These findings have led us to develop a new field of research and applications, which we named ``age-dimension technology (ADT)''. ADT has exciting potential for modifying age-related expression of genes as well as associated physiological processes, and developing novel, more effective prophylaxis or treatments for age-related diseases.

Kurachi, Kotoku; Zhang, Kezhong; Huo, Jeffrey; Ameri, Afshin; Kuwahara, Mitsuhiro; Fontaine, Jean-Marc; Yamamoto, Kei; Kurachi, Sumiko

2002-11-01

168

Comparative genomics of gene-family size in closely related bacteria  

PubMed Central

Background The wealth of genomic data in bacteria is helping microbiologists understand the factors involved in gene innovation. Among these, the expansion and reduction of gene families appears to have a fundamental role in this, but the factors influencing gene family size are unclear. Results The relative content of paralogous genes in bacterial genomes increases with genome size, largely due to the expansion of gene family size in large genomes. Bacteria undergoing genome reduction display a parallel process of redundancy elimination, by which gene families are reduced to one or a few members. Gene family size is also influenced by sequence divergence and physiological function. Large gene families show wider sequence divergence, suggesting they are probably older, and certain functions (such as metabolite transport mechanisms) are overrepresented in large families. The size of a given gene family is remarkably similar in strains of the same species and in closely related species, suggesting that homologous gene families are vertically transmitted and depend little on horizontal gene transfer (HGT). Conclusions The remarkable preservation of copy numbers in widely different ecotypes indicates a functional role for the different copies rather than simply a back-up role. When different genera are compared, the increase in phylogenetic distance and/or ecological specialization disrupts this preservation, albeit in a gradual manner and maintaining an overall similarity, which also supports this view. HGT can have an important role, however, in nonhomologous gene families, as exemplified by a comparison between saprophytic and enterohemorrhagic strains of Escherichia coli.

Pushker, Ravindra; Mira, Alex; Rodriguez-Valera, Francisco

2004-01-01

169

Spatial scaling of functional gene diversity across various microbial taxa.  

PubMed

Understanding the spatial patterns of organisms and the underlying mechanisms shaping biotic communities is a central goal in community ecology. One of the most well documented spatial patterns in plant and animal communities is the positive-power law relationship between species (or taxa) richness and area. Such taxa-area relationships (TARs) are one of the principal generalizations in ecology, and are fundamental to our understanding of the distribution of global biodiversity. However, TARs remain elusive in microbial communities, especially in soil habitats, because of inadequate sampling methodologies. Here, we describe TARs as gene-area relationships (GARs), at a whole-community level, across various microbial functional and phylogenetic groups in a forest soil, using a comprehensive functional gene array with >24,000 probes. Our analysis indicated that the forest soil microbial community exhibited a relatively flat gene-area relationship (slope z = 0.0624), but the z values varied considerably across different functional and phylogenetic groups (z = 0.0475-0.0959). However, the z values are several times lower than those commonly observed in plants and animals. These results suggest that the turnover in space of microorganisms may be, in general, lower than that of plants and animals. PMID:18509054

Zhou, Jizhong; Kang, Sanghoon; Schadt, Christopher W; Garten, Charles T

2008-05-28

170

Spatial scaling of functional gene diversity across various microbial taxa  

PubMed Central

Understanding the spatial patterns of organisms and the underlying mechanisms shaping biotic communities is a central goal in community ecology. One of the most well documented spatial patterns in plant and animal communities is the positive-power law relationship between species (or taxa) richness and area. Such taxa–area relationships (TARs) are one of the principal generalizations in ecology, and are fundamental to our understanding of the distribution of global biodiversity. However, TARs remain elusive in microbial communities, especially in soil habitats, because of inadequate sampling methodologies. Here, we describe TARs as gene–area relationships (GARs), at a whole-community level, across various microbial functional and phylogenetic groups in a forest soil, using a comprehensive functional gene array with >24,000 probes. Our analysis indicated that the forest soil microbial community exhibited a relatively flat gene–area relationship (slope z = 0.0624), but the z values varied considerably across different functional and phylogenetic groups (z = 0.0475–0.0959). However, the z values are several times lower than those commonly observed in plants and animals. These results suggest that the turnover in space of microorganisms may be, in general, lower than that of plants and animals.

Zhou, Jizhong; Kang, Sanghoon; Schadt, Christopher W.; Garten, Charles T.

2008-01-01

171

Using Text Analysis to Identify Functionally Coherent Gene Groups  

PubMed Central

The analysis of large-scale genomic information (such as sequence data or expression patterns) frequently involves grouping genes on the basis of common experimental features. Often, as with gene expression clustering, there are too many groups to easily identify the functionally relevant ones. One valuable source of information about gene function is the published literature. We present a method, neighbor divergence, for assessing whether the genes within a group share a common biological function based on their associated scientific literature. The method uses statistical natural language processing techniques to interpret biological text. It requires only a corpus of documents relevant to the genes being studied (e.g., all genes in an organism) and an index connecting the documents to appropriate genes. Given a group of genes, neighbor divergence assigns a numerical score indicating how “functionally coherent” the gene group is from the perspective of the published literature. We evaluate our method by testing its ability to distinguish 19 known functional gene groups from 1900 randomly assembled groups. Neighbor divergence achieves 79% sensitivity at 100% specificity, comparing favorably to other tested methods. We also apply neighbor divergence to previously published gene expression clusters to assess its ability to recognize gene groups that had been manually identified as representative of a common function.

Raychaudhuri, Soumya; Schutze, Hinrich; Altman, Russ B.

2002-01-01

172

The Duplicated Genes Database: Identification and Functional Annotation of Co-Localised Duplicated Genes across Genomes  

PubMed Central

Background There has been a surge in studies linking genome structure and gene expression, with special focus on duplicated genes. Although initially duplicated from the same sequence, duplicated genes can diverge strongly over evolution and take on different functions or regulated expression. However, information on the function and expression of duplicated genes remains sparse. Identifying groups of duplicated genes in different genomes and characterizing their expression and function would therefore be of great interest to the research community. The ‘Duplicated Genes Database’ (DGD) was developed for this purpose. Methodology Nine species were included in the DGD. For each species, BLAST analyses were conducted on peptide sequences corresponding to the genes mapped on a same chromosome. Groups of duplicated genes were defined based on these pairwise BLAST comparisons and the genomic location of the genes. For each group, Pearson correlations between gene expression data and semantic similarities between functional GO annotations were also computed when the relevant information was available. Conclusions The Duplicated Gene Database provides a list of co-localised and duplicated genes for several species with the available gene co-expression level and semantic similarity value of functional annotation. Adding these data to the groups of duplicated genes provides biological information that can prove useful to gene expression analyses. The Duplicated Gene Database can be freely accessed through the DGD website at http://dgd.genouest.org.

Bretaudeau, Anthony; Sallou, Olivier; Diot, Christian; Demeure, Olivier; Lecerf, Frederic

2012-01-01

173

Development and Evaluation of Functional Gene Arrays for Detection of Selected Genes in the Environment  

Microsoft Academic Search

To determine the potential of DNA array technology for assessing functional gene diversity and distribution, a prototype microarray was constructed with genes involved in nitrogen cycling: nitrite reductase (nirS and nirK) genes, ammonia mono-oxygenase (amoA) genes, and methane mono-oxygenase (pmoA) genes from pure cultures and those cloned from marine sediments. In experiments using glass slide microarrays, genes possessing less than

LIYOU WU; DOROTHEA K. THOMPSON; GUANGSHAN LI; RICHARD A. HURT; JAMES M. TIEDJE; JIZHONG ZHOU

2001-01-01

174

Executive functioning and alcohol-related aggression.  

PubMed

The primary goal of this investigation was to determine whether executive functioning (EF) would moderate the alcohol-aggression relation. Participants were 310 (152 men and 158 women) healthy social drinkers between 21 and 35 years of age. EF as well as non-EF skills were measured with 13 validated neuropsychological tests. Following the consumption of either an alcoholic or a placebo beverage, participants were tested on a modified version of the Taylor Aggression Paradigm (S. Taylor, 1967), in which mild electric shocks were received from, and administered to, a fictitious opponent. Aggressive behavior was operationalized as the shock intensities administered to the fictitious opponent. EF was negatively related to aggressive behavior for men, regardless of beverage group, even when controlling for non-EF skills. Furthermore, alcohol increased aggression only for men with lower EF scores. Finally, the mere belief that alcohol was consumed suppressed aggression for women but not for men. PMID:15535787

Giancola, Peter R

2004-11-01

175

Isolation of tumor suppressor genes from MEN-1 related neoplasms  

SciTech Connect

Multiple Endocrine Neoplasia type 1 (MEN 1) is a cancer predisposition syndrome marked by the development of tumors in specific endocrine tissues such as the pituitary, parathyroid and pancreatic islets. Genetic linkage studies have mapped the MEN 1 gene to 11q13, and allelic loss in related tumors suggests that the gene is a tumor suppressor. Because inactivation of tumor suppressors may be accompanied by underexpression, subtractive hybridization was used to isolate potential candidate genes underexpressed in MEN 1 tumors. cDNA was synthesized from tumor and normal parathyroid tissue by RT-PCR. Biotinylated tumor cDNA was used as a driver and normal cDNA as a tester in subtractive hybridization. Following annealing of the driver and tester amplicons, the biotinylated strands were removed with streptavidin. The subtracted material was then used as a probe to isolate clones from a normal pancreatic islet library. Screening 2 x 10{sup 5} plaques yielded 14 positive clones. Of 6 clones analyzed, 3 were confirmed to be underexpressed in parathyroid tumors. Sequence analysis identified 2 clones as human ribosomal protein S10 (RPS10, chromosome 6) and 1 as the islet amyloid polypeptide (1AP, chromosome 12). The precise function of human RPS10 is not known but the related RPS6 functions as a tumor suppressor in Drosophila. 1AP has been implicated in modulation of G protein activity. The remaining positive clones will be mapped to determine if any fall on chromosome 11q13, and additional subtractions with parathyroid and pancreatic islet neoplasms are underway.

Yavari, R.; Kinder, B.; Bale, A.E. [Yale Univ. School of Medicine, New Haven, CT (United States)

1994-09-01

176

Gene-environment interaction and male reproductive function  

PubMed Central

As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between and within populations, genetic variants might be important determinants of the individual susceptibility to the adverse effects of environment or lifestyle. Although the possible mechanisms of such interplay in relation to the reproductive system are largely unknown, some recent studies have indicated that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism, but the number of studies is still limited. This type of interaction studies may improve our understanding of normal physiology and help us to identify the risk factors to male reproductive malfunction. We also shortly discuss other aspects of gene-environment interaction specifically associated with the issue of reproduction, namely environmental and lifestyle factors as the cause of sperm DNA damage. It remains to be investigated to what extent such genetic changes, by natural conception or through the use of assisted reproductive techniques, are transmitted to the next generation, thereby causing increased morbidity in the offspring.

Axelsson, Jonatan; Bonde, Jens Peter; Giwercman, Yvonne L.; Rylander, Lars; Giwercman, Aleksander

2010-01-01

177

Tinman Function Is Essential for Vertebrate Heart Development: Elimination of Cardiac Differentiation by Dominant Inhibitory Mutants of the tinman-Related Genes, XNkx2-3and XNkx2-5  

Microsoft Academic Search

InDrosophila,thetinmangene is absolutely required for development of the dorsal vessel, the insect equivalent of the heart. In vertebrates, thetinmangene is represented by a small family oftinman-related sequences, some of which are expressed during embryonic heart development. At present however, the precise importance of this gene family for vertebrate heart development is unclear. Using theXenopusembryo, we have employed a dominant inhibitory

Matthew W Grow; Paul A Krieg

1998-01-01

178

EBV gene expression in an NPC-related tumour.  

PubMed

A nasopharyngeal carcinoma tumour (designated C15) propagated in nude mice has been used to generate a large cDNA library that we have analysed for Epstein-Barr virus (EBV) gene expression. No gross alterations exist in viral DNA from C15 relative to other human isolates and the large deletion present in the B95-8 'prototype' viral strain established in marmoset cells is not found; C15 contains no linear virion DNA. In the cDNA library, of the six EBV nuclear antigens (EBNAs) expressed in latently infected B-lymphocytes, only clones for EBNA-1 are found. These data are confirmed by immunoblotting. Sequence analysis shows the EBNA-1 mRNA splicing pattern in the carcinoma to differ from that observed in B-lymphocytes. Further, contrary to observations with B-cell lines, most viral transcription in the tumour is localized onto the 'rightmost' region of the conventional EBV physical map. Transcripts identified corresponding to known genes include those for the latent membrane protein (LMP), the alkaline DNA exonuclease and probably the terminal protein; major transcripts are also derived from the BamHI D fragment and the region deleted in B95-8 EBV DNA. Novel transcripts have also been identified that proceed in an anti-sense direction to genes encoding functions associated with replication, such as the viral DNA polymerase. They contain a large, hitherto unidentified, open reading frame in the viral genome that is complementary to the putative function known as BALF3 and a smaller open reading frame complementary to BALF5 (the DNA polymerase gene). From the present studies we can conclude that: (i) EBV transcription patterns in the epithelial cells vary markedly from those identified previously in B-cells, reflecting differential use of promoters or splicing patterns. (ii) Transcription is tightly regulated and restricted in the C15 tumour with many latent genes, notably EBNAs 2-6, being 'switched off.' (iii) A family of cytoplasmic RNAs are transcribed in an antisense direction to a number of existing open reading frames in the EBV genome. (iv) There are a number of mutations in C15 transcripts relative to the B95-8 genome, some of which could result in amino acid alterations in proteins. PMID:2479554

Hitt, M M; Allday, M J; Hara, T; Karran, L; Jones, M D; Busson, P; Tursz, T; Ernberg, I; Griffin, B E

1989-09-01

179

Tracing evolutionary footprints to identify novel gene functional linkages.  

PubMed

Systematic determination of gene function is an essential step in fully understanding the precise contribution of each gene for the proper execution of molecular functions in the cell. Gene functional linkage is defined as to describe the relationship of a group of genes with similar functions. With thousands of genomes sequenced, there arises a great opportunity to utilize gene evolutionary information to identify gene functional linkages. To this end, we established a computational method (called TRACE) to trace gene footprints through a gene functional network constructed from 341 prokaryotic genomes. TRACE performance was validated and successfully tested to predict enzyme functions as well as components of pathway. A so far undescribed chromosome partitioning-like protein ro03654 of an oleaginous bacteria Rhodococcus sp. RHA1 (RHA1) was predicted and verified experimentally with its deletion mutant showing growth inhibition compared to RHA1 wild type. In addition, four proteins were predicted to act as prokaryotic SNARE-like proteins, and two of them were shown to be localized at the plasma membrane. Thus, we believe that TRACE is an effective new method to infer prokaryotic gene functional linkages by tracing evolutionary events. PMID:23825567

Chen, Yong; Yang, Li; Ding, Yunfeng; Zhang, Shuyan; He, Tong; Mao, Fenglou; Zhang, Congyan; Zhang, Huina; Huo, Chaoxing; Liu, Pingsheng

2013-06-25

180

Dissecting the Gene Network of Dietary Restriction to Identify Evolutionarily Conserved Pathways and New Functional Genes  

PubMed Central

Dietary restriction (DR), limiting nutrient intake from diet without causing malnutrition, delays the aging process and extends lifespan in multiple organisms. The conserved life-extending effect of DR suggests the involvement of fundamental mechanisms, although these remain a subject of debate. To help decipher the life-extending mechanisms of DR, we first compiled a list of genes that if genetically altered disrupt or prevent the life-extending effects of DR. We called these DR–essential genes and identified more than 100 in model organisms such as yeast, worms, flies, and mice. In order for other researchers to benefit from this first curated list of genes essential for DR, we established an online database called GenDR (http://genomics.senescence.info/diet/). To dissect the interactions of DR–essential genes and discover the underlying lifespan-extending mechanisms, we then used a variety of network and systems biology approaches to analyze the gene network of DR. We show that DR–essential genes are more conserved at the molecular level and have more molecular interactions than expected by chance. Furthermore, we employed a guilt-by-association method to predict novel DR–essential genes. In budding yeast, we predicted nine genes related to vacuolar functions; we show experimentally that mutations deleting eight of those genes prevent the life-extending effects of DR. Three of these mutants (OPT2, FRE6, and RCR2) had extended lifespan under ad libitum, indicating that the lack of further longevity under DR is not caused by a general compromise of fitness. These results demonstrate how network analyses of DR using GenDR can be used to make phenotypically relevant predictions. Moreover, gene-regulatory circuits reveal that the DR–induced transcriptional signature in yeast involves nutrient-sensing, stress responses and meiotic transcription factors. Finally, comparing the influence of gene expression changes during DR on the interactomes of multiple organisms led us to suggest that DR commonly suppresses translation, while stimulating an ancient reproduction-related process.

Wuttke, Daniel; Connor, Richard; Vora, Chintan; Craig, Thomas; Li, Yang; Wood, Shona; Vasieva, Olga; Shmookler Reis, Robert; Tang, Fusheng; de Magalhaes, Joao Pedro

2012-01-01

181

Dissecting the gene network of dietary restriction to identify evolutionarily conserved pathways and new functional genes.  

PubMed

Dietary restriction (DR), limiting nutrient intake from diet without causing malnutrition, delays the aging process and extends lifespan in multiple organisms. The conserved life-extending effect of DR suggests the involvement of fundamental mechanisms, although these remain a subject of debate. To help decipher the life-extending mechanisms of DR, we first compiled a list of genes that if genetically altered disrupt or prevent the life-extending effects of DR. We called these DR-essential genes and identified more than 100 in model organisms such as yeast, worms, flies, and mice. In order for other researchers to benefit from this first curated list of genes essential for DR, we established an online database called GenDR (http://genomics.senescence.info/diet/). To dissect the interactions of DR-essential genes and discover the underlying lifespan-extending mechanisms, we then used a variety of network and systems biology approaches to analyze the gene network of DR. We show that DR-essential genes are more conserved at the molecular level and have more molecular interactions than expected by chance. Furthermore, we employed a guilt-by-association method to predict novel DR-essential genes. In budding yeast, we predicted nine genes related to vacuolar functions; we show experimentally that mutations deleting eight of those genes prevent the life-extending effects of DR. Three of these mutants (OPT2, FRE6, and RCR2) had extended lifespan under ad libitum, indicating that the lack of further longevity under DR is not caused by a general compromise of fitness. These results demonstrate how network analyses of DR using GenDR can be used to make phenotypically relevant predictions. Moreover, gene-regulatory circuits reveal that the DR-induced transcriptional signature in yeast involves nutrient-sensing, stress responses and meiotic transcription factors. Finally, comparing the influence of gene expression changes during DR on the interactomes of multiple organisms led us to suggest that DR commonly suppresses translation, while stimulating an ancient reproduction-related process. PMID:22912585

Wuttke, Daniel; Connor, Richard; Vora, Chintan; Craig, Thomas; Li, Yang; Wood, Shona; Vasieva, Olga; Shmookler Reis, Robert; Tang, Fusheng; de Magalhăes, Joăo Pedro

2012-08-09

182

Myb-Related Schizosaccharomyces pombe cdc5p Is Structurally and Functionally Conserved in Eukaryotes  

Microsoft Academic Search

Schizosaccharomyces pombe cdc5p is a Myb-related protein that is essential for G2\\/M progression. To explore the structural and functional conservation of Cdc5 throughout evolution, we isolated Cdc5-related genes and cDNAs from Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and Homo sapiens. Supporting the notion that these Cdc5 gene family members are functionally homologous to S. pombe cdc51, human and fly Cdc5

RYOMA OHI; ANNA FEOKTISTOVA; STACEY MCCANN; VIRGINIA VALENTINE; A. THOMAS LOOK; JOSEPH S. LIPSICK; KATHLEEN L. GOULD

1998-01-01

183

Ancestral MADS box genes in Sugi, Cryptomeria japonica D. Don (Taxodiaceae), homologous to the B function genes in angiosperms.  

PubMed

In flowering plants, flower organ identity is controlled by the ABC genes, including several MADS box genes. We present two MADS box genes of a conifer, Cryptomeria japonica D. Don. The genes, CjMADS1 and CjMADS2, were related to the angiosperm B function genes which determine the identities of petals and stamens. A phylogenetic analysis showed that these genes form a new clade outside the angiosperm B group, that is, PISTILLATA (PI) and APETALA3 (AP3) lineages. CjMADS1 had a PI-group specific motif and CjMADS2 had AP3-group specific motifs at the C terminal end, respectively. CjMADS1 was expressed in male strobili (or cones) throughout its development, while CjMADS2 was transiently expressed during male strobilus development. The specific expression in the male reproductive organ indicated that the B function is maintained in gymnosperms. Our cladistic analysis suggests that the gene duplication event which generated B function gene lineages predates the divergence of angiosperms and gymnosperms and that the gene duplication which produced the two genes of C. japonica occurred in an ancestral conifer species. PMID:11427675

Fukui, M; Futamura, N; Mukai, Y; Wang, Y; Nagao, A; Shinohara, K

2001-06-01

184

Nonviral gene transfection nanoparticles: function and applications in the brain  

Microsoft Academic Search

In vivo transfer and expression of foreign genes allows for the elucidation of functions of genes in living organisms and generation of disease models in animals that more closely resemble the etiology of human diseases. Gene therapy holds promise for the cure of a number of diseases at the fundamental level. Synthetic “nonviral” materials are fast gaining popularity as safe

Indrajit Roy; Michal K. Stachowiak; Earl J. Bergey

2008-01-01

185

Mining functionally relevant gene sets for analyzing physiologically novel clinical expression data.  

PubMed

Gene set analyses have become a standard approach for increasing the sensitivity of transcriptomic studies. However, analytical methods incorporating gene sets require the availability of pre-defined gene sets relevant to the underlying physiology being studied. For novel physiological problems, relevant gene sets may be unavailable or existing gene set databases may bias the results towards only the best-studied of the relevant biological processes. We describe a successful attempt to mine novel functional gene sets for translational projects where the underlying physiology is not necessarily well characterized in existing annotation databases. We choose targeted training data from public expression data repositories and define new criteria for selecting biclusters to serve as candidate gene sets. Many of the discovered gene sets show little or no enrichment for informative Gene Ontology terms or other functional annotation. However, we observe that such gene sets show coherent differential expression in new clinical test data sets, even if derived from different species, tissues, and disease states. We demonstrate the efficacy of this method on a human metabolic data set, where we discover novel, uncharacterized gene sets that are diagnostic of diabetes, and on additional data sets related to neuronal processes and human development. Our results suggest that our approach may be an efficient way to generate a collection of gene sets relevant to the analysis of data for novel clinical applications where existing functional annotation is relatively incomplete. PMID:21121032

Turcan, Sevin; Vetter, Douglas E; Maron, Jill L; Wei, Xintao; Slonim, Donna K

2011-01-01

186

Gene delivery by functional inorganic nanocarriers.  

PubMed

Gene delivery into cells to elicit cellular response has received a great attention recently. Viruses, lipids, peptides, cationic polymers and certain inorganic nanomaterials have been reported as gene delivery vectors. In this review, we focus on the recent literature on gene delivery using inorganic nanoparticles. This emerging field of study is concisely summarized and illustrated by selected examples and recent patents. New approaches and directions towards the practical use of multifunctional nanocarriers are highlighted. PMID:22670611

Loh, Xian Jun; Lee, Tung-Chun

2012-08-01

187

Gene discovery and gene function assignment in filamentous fungi  

PubMed Central

Filamentous fungi are a large group of diverse and economically important microorganisms. Large-scale gene disruption strategies developed in budding yeast are not applicable to these organisms because of their larger genomes and lower rate of targeted integration (TI) during transformation. We developed transposon-arrayed gene knockouts (TAGKO) to discover genes and simultaneously create gene disruption cassettes for subsequent transformation and mutant analysis. Transposons carrying a bacterial and fungal drug resistance marker are used to mutagenize individual cosmids or entire libraries in vitro. Cosmids are annotated by DNA sequence analysis at the transposon insertion sites, and cosmid inserts are liberated to direct insertional mutagenesis events in the genome. Based on saturation analysis of a cosmid insert and insertions in a fungal cosmid library, we show that TAGKO can be used to rapidly identify and mutate genes. We further show that insertions can create alterations in gene expression, and we have used this approach to investigate an amino acid oxidation pathway in two important fungal phytopathogens.

Hamer, Lisbeth; Adachi, Kiichi; Montenegro-Chamorro, Maria V.; Tanzer, Matthew M.; Mahanty, Sanjoy K.; Lo, Clive; Tarpey, Rex W.; Skalchunes, Amy R.; Heiniger, Ryan W.; Frank, Sheryl A.; Darveaux, Blaise A.; Lampe, David J.; Slater, Ted M.; Ramamurthy, Lakshman; DeZwaan, Todd M.; Nelson, Grant H.; Shuster, Jeffrey R.; Woessner, Jeffrey; Hamer, John E.

2001-01-01

188

Function for Hedgehog Genes in Zebrafish Retinal Development  

Microsoft Academic Search

The hedgehog (hh) genes encode secreted signaling proteins that have important developmental functions in vertebrates and invertebrates. In Drosophila, expression of hh coordinates retinal development by propagating a wave of photoreceptor differentiation across the eye primordium. Here we report that two vertebrate hh genes, sonic hedgehog (shh) and tiggy-winkle hedgehog (twhh), may perform similar functions in the developing zebrafish. Both

Deborah L. Stenkamp; Ruth A. Frey; Shubhangi N. Prabhudesai; Pamela A. Raymond

2000-01-01

189

Reproduction-related genes in the pearl oyster genome.  

PubMed

Molluscan reproduction has been a target of biological research because of the various reproductive strategies that have evolved in this phylum. It has also been studied for the development of fisheries technologies, particularly aquaculture. Although fundamental processes of reproduction in other phyla, such as vertebrates and arthropods, have been well studied, information on the molecular mechanisms of molluscan reproduction remains limited. The recently released draft genome of the pearl oyster Pinctada fucata provides a novel and powerful platform for obtaining structural information on the genes and proteins involved in bivalve reproduction. In the present study, we analyzed the pearl oyster draft genome to screen reproduction-related genes. Analysis was mainly conducted for genes reported from other molluscs for encoding orthologs of reproduction-related proteins in other phyla. The gene search in the P. fucata gene models (version 1.1) and genome assembly (version 1.0) were performed using Genome Browser and BLAST software. The obtained gene models were then BLASTP searched against a public database to confirm the best-hit sequences. As a result, more than 40 gene models were identified with high accuracy to encode reproduction-related genes reported for P. fucata and other molluscs. These include vasa, nanos, doublesex- and mab-3-related transcription factor, 5-hydroxytryptamine (5-HT) receptors, vitellogenin, estrogen receptor, and others. The set of reproduction-related genes of P. fucata identified in the present study constitute a new tool for research on bivalve reproduction at the molecular level. PMID:24125647

Matsumoto, Toshie; Masaoka, Tetsuji; Fujiwara, Atsushi; Nakamura, Yoji; Satoh, Nori; Awaji, Masahiko

2013-10-01

190

Combining classifiers to predict gene function in Arabidopsis thaliana using large-scale gene expression measurements  

Microsoft Academic Search

Background: Arabidopsis thaliana is the model species of current plant genomic research with a genome size of 125 Mb and approximately 28,000 genes. The function of half of these genes is currently unknown. The purpose of this study is to infer gene function in Arabidopsis using machine-learning algorithms applied to large-scale gene expression data sets, with the goal of identifying

Hui Lan; Rachel Carson; Nicholas J. Provart; Anthony J. Bonner

2007-01-01

191

Field measurement of head related transfer functions  

NASA Astrophysics Data System (ADS)

This effort sought to refine and simplify techniques for generating acoustic signals that could be used in 3-D auditory displays. Such signals are presented to a listener over headphones and create the illusion of a virtual sound source at a predetermined position in 3-D space. The signals are generated digitally, using algorithms based on the acoustic effects of human outer ear structures on sound waves reaching the ears. To date, the main area of difficulty inhibiting development of practical (3-D) displays is in obtaining estimates of these outer ear effects. The work was divided into three areas: (1) acoustic measurements of free field-to-eardrum transfer functions (also called head related transfer functions, of HRTFs); (2) analysis of HRTFs; and (3) psychophysical assessment of human performance in sound localization tasks involving stimuli presented both in real and in simulated (virtual) auditory space. The focus was on evaluating means for making HRTF measurements faster and easier, thus simplifying synthesis of auditory stimuli for 3-D displays.

Wightman, Frederic; Kistler, Doris J.

1990-04-01

192

Symbiosis-related pea genes modulate fungal and plant gene expression during the arbuscule stage of mycorrhiza with Glomus intraradices.  

PubMed

The arbuscular mycorrhiza association results from a successful interaction between genomes of the plant and fungal symbiotic partners. In this study, we analyzed the effect of inactivation of late-stage symbiosis-related pea genes on symbiosis-associated fungal and plant molecular responses in order to gain insight into their role in the functional mycorrhizal association. The expression of a subset of ten fungal and eight plant genes, previously reported to be activated during mycorrhiza development, was compared in Glomus intraradices-inoculated wild-type and isogenic genotypes of pea mutated for the PsSym36, PsSym33, and PsSym40 genes where arbuscule formation is inhibited or fungal turnover modulated, respectively. Microdissection was used to corroborate arbuscule-related fungal gene expression. Molecular responses varied between pea genotypes and with fungal development. Most of the fungal genes were downregulated when arbuscule formation was defective, and several were upregulated with more rapid fungal development. Some of the plant genes were also affected by inactivation of the PsSym36, PsSym33, and PsSym40 loci, but in a more time-dependent way during root colonization by G. intraradices. Results indicate a role of the late-stage symbiosis-related pea genes not only in mycorrhiza development but also in the symbiotic functioning of arbuscule-containing cells. PMID:20094894

Kuznetsova, Elena; Seddas-Dozolme, Pascale M A; Arnould, Christine; Tollot, Marie; van Tuinen, Diederik; Borisov, Alexey; Gianinazzi, Silvio; Gianinazzi-Pearson, Vivienne

2010-01-22

193

Reconstruction of a Functional Human Gene Network, with an Application for Prioritizing Positional Candidate Genes  

PubMed Central

Most common genetic disorders have a complex inheritance and may result from variants in many genes, each contributing only weak effects to the disease. Pinpointing these disease genes within the myriad of susceptibility loci identified in linkage studies is difficult because these loci may contain hundreds of genes. However, in any disorder, most of the disease genes will be involved in only a few different molecular pathways. If we know something about the relationships between the genes, we can assess whether some genes (which may reside in different loci) functionally interact with each other, indicating a joint basis for the disease etiology. There are various repositories of information on pathway relationships. To consolidate this information, we developed a functional human gene network that integrates information on genes and the functional relationships between genes, based on data from the Kyoto Encyclopedia of Genes and Genomes, the Biomolecular Interaction Network Database, Reactome, the Human Protein Reference Database, the Gene Ontology database, predicted protein-protein interactions, human yeast two-hybrid interactions, and microarray coexpressions. We applied this network to interrelate positional candidate genes from different disease loci and then tested 96 heritable disorders for which the Online Mendelian Inheritance in Man database reported at least three disease genes. Artificial susceptibility loci, each containing 100 genes, were constructed around each disease gene, and we used the network to rank these genes on the basis of their functional interactions. By following up the top five genes per artificial locus, we were able to detect at least one known disease gene in 54% of the loci studied, representing a 2.8-fold increase over random selection. This suggests that our method can significantly reduce the cost and effort of pinpointing true disease genes in analyses of disorders for which numerous loci have been reported but for which most of the genes are unknown.

Franke, Lude; Bakel, Harm van; Fokkens, Like; de Jong, Edwin D.; Egmont-Petersen, Michael; Wijmenga, Cisca

2006-01-01

194

Cloning and functional analysis of three genes encoding polygalacturonase-inhibiting proteins from Capsicum annuum and transgenic CaPGIP1 in tobacco in relation to increased resistance to two fungal pathogens.  

PubMed

Polygalacturonase-inhibiting proteins (PGIPs) are plant cell wall glycoproteins that can inhibit fungal endopolygalacturonases (PGs). The PGIPs directly reduce the aggressive potential of PGs. Here, we isolated and functionally characterized three members of the pepper (Capsicum annuum) PGIP gene family. Each was up-regulated at a different time following stimulation of the pepper leaves by Phytophthora capcisi and abiotic stresses including salicylic acid, methyl jasmonate, abscisic acid, wounding and cold treatment. Purified recombinant proteins individually inhibited activity of PGs produced by Alternaria alternata and Colletotrichum nicotianae, respectively, and virus-induced gene silencing in pepper conferred enhanced susceptibility to P. capsici. Because three PGIP genes acted similarily in conferring resistance to infection by P. capsici, and because individually purified proteins showed consistent inhibition against PG activity of both pathogens, CaPGIP1 was selected for manipulating transgenic tobacco. The crude proteins from transgenic tobacco exhibited distinct enhanced resistance to PG activity of both fungi. Moreover, the transgenic tobacco showed effective resistance to infection and a significant reduction in the number of infection sites, number of lesions and average size of lesions in the leaves. All results suggest that CaPGIPs may be involved in plant defense response and play an important role in a plant's resistance to disease. PMID:23334855

Wang, Xiuju; Zhu, Xiaoping; Tooley, Paul; Zhang, Xiuguo

2013-01-19

195

Biological Functions of the Genes in the Mammaprint Breast Cancer Profile Reflect the Hallmarks of Cancer  

PubMed Central

Background: MammaPrint was developed as a diagnostic tool to predict risk of breast cancer metastasis using the expression of 70 genes. To better understand the tumor biology assessed by MammaPrint, we interpreted the biological functions of the 70-genes and showed how the genes reflect the six hallmarks of cancer as defined by Hanahan and Weinberg. Results: We used a bottom-up system biology approach to elucidate how the cellular processes reflected by the 70-genes work together to regulate tumor activities and progression. The biological functions of the genes were analyzed using literature research and several bioinformatics tools. Protein-protein interaction network analyses indicated that the 70-genes form highly interconnected networks and that their expression levels are regulated by key tumorigenesis related genes such as TP53, RB1, MYC, JUN and CDKN2A. The biological functions of the genes could be associated with the essential steps necessary for tumor progression and metastasis, and cover the six well-defined hallmarks of cancer, reflecting the acquired malignant characteristics of a cancer cell along with tumor progression and metastasis-related biological activities. Conclusion: Genes in the MammaPrint gene signature comprehensively measure the six hallmarks of cancer-related biology. This finding establishes a link between a molecular signature and the underlying molecular mechanisms of tumor cell progression and metastasis.

Tian, Sun; Roepman, Paul; van't Veer, Laura J; Bernards, Rene; de Snoo, Femke; Glas, Annuska M

2010-01-01

196

A hybrid approach to gene ranking using gene relation networks derived from literature for the identification of disease gene markers.  

PubMed

For the identification of gene markers involved in diseases, microarray expression profiles have been widely used to prioritize genes. In this paper, we propose a novel approach to gene ranking that employs gene relation network derived from literature along with microarray expression scores to calculate ranking statistics of individual genes. In particular, the gene relation network is constructed from literature by applying syntactic analysis and co-occurrence method in a hybrid manner. For evaluation, the proposed method was tested with publicly available prostate cancer data. The result shows that our method is superior to other existing approaches. PMID:23155760

Shin, Miyoung; Lee, Hyungmin; Hong, Munpyo

2012-01-01

197

Functional Evolution of cis-Regulatory Modules at a Homeotic Gene in Drosophila  

Microsoft Academic Search

It is a long-held belief in evolutionary biology that the rate of molecular evolution for a given DNA sequence is inversely related to the level of functional constraint. This belief holds true for the protein-coding homeotic (Hox) genes originally discovered in Drosophila melanogaster. Expression of the Hox genes in Drosophila embryos is essential for body patterning and is controlled by

Margaret C. W. Ho; Holly Johnsen; Sara E. Goetz; Benjamin J. Schiller; Esther Bae; Diana A. Tran; Andrey S. Shur; John M. Allen; Christoph Rau; Welcome Bender; William W. Fisher; Susan E. Celniker; Robert A. Drewell

2009-01-01

198

Functional Hypervariability and Gene Diversity of Cardioactive Neuropeptides*  

PubMed Central

Crustacean cardioactive peptide (CCAP) and related peptides are multifunctional regulatory neurohormones found in invertebrates. We isolated a CCAP-related peptide (conoCAP-a, for cone snail CardioActive Peptide) and cloned the cDNA of its precursor from venom of Conus villepinii. The precursor of conoCAP-a encodes for two additional CCAP-like peptides: conoCAP-b and conoCAP-c. This multi-peptide precursor organization is analogous to recently predicted molluscan CCAP-like preprohormones, and suggests a mechanism for the generation of biological diversification without gene amplification. While arthropod CCAP is a cardio-accelerator, we found that conoCAP-a decreases the heart frequency in Drosophila larvae, demonstrating that conoCAP-a and CCAP have opposite effects. Intravenous injection of conoCAP-a in rats caused decreased heart frequency and blood pressure in contrast to the injection of CCAP, which did not elicit any cardiac effect. Perfusion of rat ventricular cardiac myocytes with conoCAP-a decreased systolic calcium, indicating that conoCAP-a cardiac negative inotropic effects might be mediated via impairment of intracellular calcium trafficking. The contrasting cardiac effects of conoCAP-a and CCAP indicate that molluscan CCAP-like peptides have functions that differ from those of their arthropod counterparts. Molluscan CCAP-like peptides sequences, while homologous, differ between taxa and have unique sequences within a species. This relates to the functional hypervariability of these peptides as structure activity relationship studies demonstrate that single amino acids variations strongly affect cardiac activity. The discovery of conoCAPs in cone snail venom emphasizes the significance of their gene plasticity to have mutations as an adaptive evolution in terms of structure, cellular site of expression, and physiological functions.

Moller, Carolina; Melaun, Christian; Castillo, Cecilia; Diaz, Mary E.; Renzelman, Chad M.; Estrada, Omar; Kuch, Ulrich; Lokey, Scott; Mari, Frank

2010-01-01

199

Identification of immunity related genes to study the Physalis peruviana--Fusarium oxysporum pathosystem.  

PubMed

The Cape gooseberry (Physalisperuviana L) is an Andean exotic fruit with high nutritional value and appealing medicinal properties. However, its cultivation faces important phytosanitary problems mainly due to pathogens like Fusarium oxysporum, Cercosporaphysalidis and Alternaria spp. Here we used the Cape gooseberry foliar transcriptome to search for proteins that encode conserved domains related to plant immunity including: NBS (Nucleotide Binding Site), CC (Coiled-Coil), TIR (Toll/Interleukin-1 Receptor). We identified 74 immunity related gene candidates in P. peruviana which have the typical resistance gene (R-gene) architecture, 17 Receptor like kinase (RLKs) candidates related to PAMP-Triggered Immunity (PTI), eight (TIR-NBS-LRR, or TNL) and nine (CC-NBS-LRR, or CNL) candidates related to Effector-Triggered Immunity (ETI) genes among others. These candidate genes were categorized by molecular function (98%), biological process (85%) and cellular component (79%) using gene ontology. Some of the most interesting predicted roles were those associated with binding and transferase activity. We designed 94 primers pairs from the 74 immunity-related genes (IRGs) to amplify the corresponding genomic regions on six genotypes that included resistant and susceptible materials. From these, we selected 17 single band amplicons and sequenced them in 14 F. oxysporum resistant and susceptible genotypes. Sequence polymorphisms were analyzed through preliminary candidate gene association, which allowed the detection of one SNP at the PpIRG-63 marker revealing a nonsynonymous mutation in the predicted LRR domain suggesting functional roles for resistance. PMID:23844210

Enciso-Rodríguez, Felix E; González, Carolina; Rodríguez, Edwin A; López, Camilo E; Landsman, David; Barrero, Luz Stella; Marińo-Ramírez, Leonardo

2013-07-03

200

Relating the Implementation Techniques of Functional and Functional Logic Languages  

Microsoft Academic Search

Functional logic languages are declarative programming languages that integratethe programming paradigms of functional and logic languages within a single framework.They are extensions of functional languages with principles derived from logicprogramming. Narrowing, the evaluation mechanism of functional logic languages,can be defined as a generalization of reduction, the evaluation mechanism of purelyfunctional languages. The unidirectional pattern matching, which is used for parameter...

Rita Loogen; RWTH Aachen

1993-01-01

201

Family business: the multidrug-resistance related protein (MRP) ABC transporter genes in Arabidopsis thaliana  

Microsoft Academic Search

Despite the completion of the sequencing of the entire genome of Arabidopsis thaliana (L.) Heynh., the exact determination of each single gene and its function remains an open question. This is especially true for multigene families. An approach that combines analysis of genomic structure, expression data and functional genomics to ascertain the role of the members of the multidrug-resistance-related protein

Üner H. Kolukisaoglu; Lucien Bovet; Markus Klein; Thomas Eggmann; Markus Geisler; Dierk Wanke; Enrico Martinoia; Burkhard Schulz

2002-01-01

202

A spermatogenesis-related gene expression profile in human spermatozoa and its potential clinical applications.  

PubMed

Spermatogenesis is an essential stage in the human reproductive process. In a previously study aiming to determine which genes might be involved in spermatogenesis, we compared the gene expression profiles of adult and fetal testes by hybridizing cDNA probes prepared from adult and fetal testes to membranes dotted with gene clones derived from a commercial human testis library. We identified 266 differentially expressed genes that showed higher expression levels in adult testes, indicating their potential roles in spermatogenesis. In the present study, we applied the same cDNA microarray technique to the analysis of gene expression in the spermatozoa of normal fertile men and found 149 genes that were expressed at higher levels in adult testis. A further study of five sperm motility-related genes selected from this profile by real-time PCR revealed that there was significant difference in the expression levels of two genes ( TPX-1, testis-specific protein 1 and LDHC, lactate dehydrogenase C, transcript variant 1) between normal ( n=29) and motility impaired ( n=24) semen samples, indicating that these genes are involved in sperm function. Our results demonstrated that spermatogenesis-related gene profiling could help to assess sperm quality in humans, and further study of these genes will help us to elucidate the mechanisms involved in spermatogenesis and diseases relating to human infertility. PMID:14985855

Wang, Hui; Zhou, Zuomin; Xu, Min; Li, Jianmin; Xiao, Junhua; Xu, Zhi-Yang; Sha, Jiahao

2004-02-24

203

Characterization of age-related gene expression profiling in bone marrow and epididymal adipocytes  

PubMed Central

Background While an increase in bone marrow adiposity is associated with age-related bone disease, the function of bone marrow adipocytes has not been studied. The aim of this study was to characterize and compare the age-related gene expression profiles in bone marrow adipocytes and epididymal adipocytes. Results A total of 3918 (13.7%) genes were differentially expressed in bone marrow adipocytes compared to epididymal adipocytes. Bone marrow adipocytes revealed a distinct gene profile with low expression of adipocyte-specific genes peroxisome proliferator-activated receptor gamma (PPAR?), fatty acid binding protein 4 (FABP4), perilipin (Plin1), adipsin (CFD) and high expression of genes associated with early adipocyte differentiation (CCAAT/enhancer binding protein beta (C/EBP?), regulator of G-protein signaling 2 (RGS2). In addition, a number of genes including secreted frizzled related protein 4 (SFRP4), tumor necrosis factor ? (TNF?), transforming growth factor beta 1(TGF?1), G-protein coupled receptor 109A (GPR109A) and interleukin 6 (IL-6), that could affect adipose-derived signaling to bone are markedly increased in bone marrow adipocytes. Age had a substantial effect on genes associated with mitochondria function and inflammation in bone marrow adipocytes. Twenty seven genes were significantly changed with age in both adipocyte depots. Among these genes, IL6 and GPR109A were significantly reduced with age in both adipocyte depots. Conclusions Overall, gene profiling reveals a unique phenotype for primary bone marrow adipocytes characterized by low adipose-specific gene expression and high expression of inflammatory response genes. Bone marrow and epididymal adipocytes share a common pathway in response to aging in mice, but age has a greater impact on global gene expression in epididymal than in bone marrow adipocytes. Genes that are differentially expressed at greater levels in the bone marrow are highly regulated with age.

2011-01-01

204

The function and evolution of Msx genes: pointers and paradoxes  

Microsoft Academic Search

The Msx genes of vertebrates comprise a small family of chromosomally unlinked homeobox-containing genes related to the Drosophila gene muscle-segment homeobox (msb). Despite their ancient pedigree, the Msx genes are expressed in a range of vertebrate-specific tissues, including neural crest, cranial sensory placodes, bone and teeth. They are active in numerous systems, which have been used as models to study

Duncan Davidson

1995-01-01

205

Suppression subtractive hybridization identified differentially expressed genes in lung adenocarcinoma: ERGIC3 as a novel lung cancer-related gene  

PubMed Central

Background To understand the carcinogenesis caused by accumulated genetic and epigenetic alterations and seek novel biomarkers for various cancers, studying differentially expressed genes between cancerous and normal tissues is crucial. In the study, two cDNA libraries of lung cancer were constructed and screened for identification of differentially expressed genes. Methods Two cDNA libraries of differentially expressed genes were constructed using lung adenocarcinoma tissue and adjacent nonmalignant lung tissue by suppression subtractive hybridization. The data of the cDNA libraries were then analyzed and compared using bioinformatics analysis. Levels of mRNA and protein were measured by quantitative real-time polymerase chain reaction (q-RT-PCR) and western blot respectively, as well as expression and localization of proteins were determined by immunostaining. Gene functions were investigated using proliferation and migration assays after gene silencing and gene over-expression. Results Two libraries of differentially expressed genes were obtained. The forward-subtracted library (FSL) and the reverse-subtracted library (RSL) contained 177 and 59 genes, respectively. Bioinformatic analysis demonstrated that these genes were involved in a wide range of cellular functions. The vast majority of these genes were newly identified to be abnormally expressed in lung cancer. In the first stage of the screening for 16 genes, we compared lung cancer tissues with their adjacent non-malignant tissues at the mRNA level, and found six genes (ERGIC3, DDR1, HSP90B1, SDC1, RPSA, and LPCAT1) from the FSL were significantly up-regulated while two genes (GPX3 and TIMP3) from the RSL were significantly down-regulated (P?genes may provide the basis for new insights or clues for finding novel lung cancer-related genes; several genes were newly found in lung cancer with ERGIC3 seeming a novel lung cancer-related gene. ERGIC3 may play an active role in the development and progression of lung cancer.

2013-01-01

206

Inferring the functions of longevity genes with modular subnetwork biomarkers of Caenorhabditis elegans aging  

PubMed Central

A central goal of biogerontology is to identify robust gene-expression biomarkers of aging. Here we develop a method where the biomarkers are networks of genes selected based on age-dependent activity and a graph-theoretic property called modularity. Tested on Caenorhabditis elegans, our algorithm yields better biomarkers than previous methods - they are more conserved across studies and better predictors of age. We apply these modular biomarkers to assign novel aging-related functions to poorly characterized longevity genes.

2010-01-01

207

Heterologous virus-induced gene silencing as a promising approach in plant functional genomics  

Microsoft Academic Search

VIGS (virus induced gene silencing) is considered as a powerful genomics tool for characterizing the function of genes in\\u000a a few closely related plant species. The investigations have been carried out mainly in order to test if a pre-existing VIGS\\u000a vector can serve as an efficient tool for gene silencing in a diverse array of plant species. Another route of

Seied Ali Hosseini Tafreshi; Mansour Shariati; Mohammad Reza Mofid; Mojtaba Khayam Nekui; Abolghasem Esmaeili

208

Identification of genes related to the development of bamboo rhizome bud  

PubMed Central

Bamboo (Phyllostachys praecox) is one of the largest members of the grass family Poaceae, and is one of the most economically important crops in Asia. However, complete knowledge of bamboo development and its molecular mechanisms is still lacking. In the present study, the differences in anatomical structure among rhizome buds, rhizome shoots, and bamboo shoots were compared, and several genes related to the development of the bamboo rhizome bud were identified. The rice cross-species microarray hybridization showed a total of 318 up-regulated and 339 down-regulated genes, including those involved in regulation and signalling, metabolism, and stress, and also cell wall-related genes, in the bamboo rhizome buds versus the leaves. By referring to the functional dissection of the homologous genes from Arabidopsis and rice, the putative functions of the 52 up-regulated genes in the bamboo rhizome bud were described. Six genes related to the development of the bamboo rhizome bud were further cloned and sequenced. These show 66–90% nucleotide identity and 68–98% amino acid identity with the homologous rice genes. The expression patterns of these genes revealed significant differences in rhizome shoots, rhizome buds, bamboo shoots, leaves, and young florets. Furthermore, in situ hybridization showed that the PpRLK1 gene is expressed in the procambium and is closely related to meristem development of bamboo shoots. The PpHB1 gene is expressed at the tips of bamboo shoots and procambium, and is closely related to rhizome bud formation and procambial development. To our knowledge, this is the first report that uses rice cross-species hybridization to identify genes related to bamboo rhizome bud development, and thereby contributes to the further understanding of the molecular mechanism involved in bamboo rhizome bud development.

Wang, Kuihong; Peng, Huazheng; Lin, Erpei; Jin, Qunying; Hua, Xiqi; Yao, Sheng; Bian, Hongwu; Han, Ning; Pan, Jianwei; Wang, Junhui; Deng, Mingjuan; Zhu, Muyuan

2010-01-01

209

FUNCTIONAL NANOPARTICLES FOR MOLECULAR IMAGING GUIDED GENE DELIVERY  

PubMed Central

Gene therapy has great potential to bring tremendous changes in treatment of various diseases and disorders. However, one of the impediments to successful gene therapy is the inefficient delivery of genes to target tissues and the inability to monitor delivery of genes and therapeutic responses at the targeted site. The emergence of molecular imaging strategies has been pivotal in optimizing gene therapy; since it can allow us to evaluate the effectiveness of gene delivery noninvasively and spatiotemporally. Due to the unique physiochemical properties of nanomaterials, numerous functional nanoparticles show promise in accomplishing gene delivery with the necessary feature of visualizing the delivery. In this review, recent developments of nanoparticles for molecular imaging guided gene delivery are summarized.

Liu, Gang; Swierczewska, Magdalena; Lee, Seulki; Chen, Xiaoyuan

2010-01-01

210

Complementation of an RNase P RNA (rnpB) gene deletion in Escherichia coli by homologous genes from distantly related eubacteria.  

PubMed Central

We report the construction of a strain of Escherichia coli in which the only functional gene for the RNA moiety of RNase P (rnpB) resides on a plasmid that is temperature sensitive for replication. The chromosomal RNase P RNA gene was replaced with a chloramphenicol acetyltransferase gene. The conditionally lethal phenotype of this strain was suppressed by plasmids that carry RNase P RNA genes from some distantly related eubacteria, including Alcaligenes eutrophus, Bacillus subtilis, and Chromatium vinosum. Thus, the rnpB genes from these organisms are capable of functioning as the sole source of RNase P RNA in E. coli. The rnpB genes of some other organisms (Agrobacterium tumefaciens, Pseudomonas fluorescens, Bacillus brevis, Bacillus megaterium, and Bacillus stearothermophilus) could not replace the E. coli gene. The significance of these findings as they relate to RNase P RNA structure and function and the utility of the described strain for genetic studies are discussed. Images

Waugh, D S; Pace, N R

1990-01-01

211

Inferring gene transcriptional modulatory relations: a genetical genomics approach  

Microsoft Academic Search

Bayesian network modeling is a promising approach to define and evaluate gene expression circuits in diverse tissues and cell types under different experimental conditions. The power and practicality of this approach can be improved by restricting the number of potential interactions among genes and by defining causal relations before evaluating posterior probabilities for billions of networks. A newly developed genetical

Hongqiang Li; Lu Lu; Kenneth F. Manly; Elissa J. Chesler; Lei Bao; Jintao Wang; Mi Zhou; Robert W. Williams; Yan Cui

2005-01-01

212

A metabolic gene cluster in Lotus japonicus discloses novel enzyme functions and products in triterpene biosynthesis.  

PubMed

Genes for triterpene biosynthetic pathways exist as metabolic gene clusters in oat and Arabidopsis thaliana plants. We characterized the presence of an analogous gene cluster in the model legume Lotus japonicus. In the genomic regions flanking the oxidosqualene cyclase AMY2 gene, genes for two different classes of cytochrome P450 and a gene predicted to encode a reductase were identified. Functional characterization of the cluster genes was pursued by heterologous expression in Nicotiana benthamiana. The gene expression pattern was studied under different developmental and environmental conditions. The physiological role of the gene cluster in nodulation and plant development was studied in knockdown experiments. A novel triterpene structure, dihydrolupeol, was produced by AMY2. A new plant cytochrome P450, CYP71D353, which catalyses the formation of 20-hydroxybetulinic acid in a sequential three-step oxidation of 20-hydroxylupeol was characterized. The genes within the cluster are highly co-expressed during root and nodule development, in hormone-treated plants and under various environmental stresses. A transcriptional gene silencing mechanism that appears to be involved in the regulation of the cluster genes was also revealed. A tightly co-regulated cluster of functionally related genes is involved in legume triterpene biosynthesis, with a possible role in plant development. PMID:23909862

Krokida, Afrodite; Delis, Costas; Geisler, Katrin; Garagounis, Constantine; Tsikou, Daniela; Peńa-Rodríguez, Luis M; Katsarou, Dimitra; Field, Ben; Osbourn, Anne E; Papadopoulou, Kalliope K

2013-07-26

213

Quantitative analysis of gene function in the Drosophila embryo.  

PubMed Central

The specific functions of gene products frequently depend on the developmental context in which they are expressed. Thus, studies on gene function will benefit from systems that allow for manipulation of gene expression within model systems where the developmental context is well defined. Here we describe a system that allows for genetically controlled overexpression of any gene of interest under normal physiological conditions in the early Drosophila embryo. This regulated expression is achieved through the use of Drosophila lines that express a maternal mRNA for the yeast transcription factor GAL4. Embryos derived from females that express GAL4 maternally activate GAL4-dependent UAS transgenes at uniform levels throughout the embryo during the blastoderm stage of embryogenesis. The expression levels can be quantitatively manipulated through the use of lines that have different levels of maternal GAL4 activity. Specific phenotypes are produced by expression of a number of different developmental regulators with this system, including genes that normally do not function during Drosophila embryogenesis. Analysis of the response to overexpression of runt provides evidence that this pair-rule segmentation gene has a direct role in repressing transcription of the segment-polarity gene engrailed. The maternal GAL4 system will have applications both for the measurement of gene activity in reverse genetic experiments as well as for the identification of genetic factors that have quantitative effects on gene function in vivo.

Tracey, W D; Ning, X; Klingler, M; Kramer, S G; Gergen, J P

2000-01-01

214

Functional second genes generated by retrotransposition of the X-linked ribosomal protein genes  

Microsoft Academic Search

We have identified a new class of ribosomal protein (RP) genes that appear to have been retro- transposed from X-linked RP genes. Mammalian ribosomes are composed of four RNA species and 79 different proteins. Unlike RNA constituents, each protein is typically encoded by a single intron- containing gene. Here we describe functional auto- somal copies of the X-linked human RP

Tamayo Uechi; Noriko Maeda; Tatsuo Tanaka; Naoya Kenmochi

2002-01-01

215

Combining gene expression profiles and protein–protein interaction data to infer gene functions  

Microsoft Academic Search

The ever-increasing flow of gene expression profiles and protein–protein interactions has catalyzed many computational approaches for inference of gene functions. Despite all the efforts, there is still room for improvement, for the information enriched in each biological data source has not been exploited to its fullness. A composite method is proposed for classifying unannotated genes based on expression data and

Kang Tu; Hui Yu; Yi-Xue Li

2006-01-01

216

Information-based methods for predicting gene function from systematic gene knock-downs  

PubMed Central

Background The rapid annotation of genes on a genome-wide scale is now possible for several organisms using high-throughput RNA interference assays to knock down the expression of a specific gene. To date, dozens of RNA interference phenotypes have been recorded for the nematode Caenorhabditis elegans. Although previous studies have demonstrated the merit of using knock-down phenotypes to predict gene function, it is unclear how the data can be used most effectively. An open question is how to optimally make use of phenotypic observations, possibly in combination with other functional genomics datasets, to identify genes that share a common role. Results We compared several methods for detecting gene-gene functional similarity from phenotypic knock-down profiles. We found that information-based measures, which explicitly incorporate a phenotype's genomic frequency when calculating gene-gene similarity, outperform non-information-based methods. We report the presence of newly predicted modules identified from an integrated functional network containing phenotypic congruency links derived from an information-based measure. One such module is a set of genes predicted to play a role in regulating body morphology based on their multiply-supported interactions with members of the TGF-? signaling pathway. Conclusion Information-based metrics significantly improve the comparison of phenotypic knock-down profiles, based upon their ability to enhance gene function prediction and identify novel functional modules.

Weirauch, Matthew T; Wong, Christopher K; Byrne, Alexandra B; Stuart, Joshua M

2008-01-01

217

Wnt Pathway-Related Gene Expression in Inflammatory Bowel Disease  

Microsoft Academic Search

The purpose of this study was to examine the expression of Wnt pathway-related genes in patients with ulcerative colitis (UC).\\u000a RNA from colonoscopic biopsies from noninflammatory bowel disease (non-IBD) subjects and UC patients were obtained and examined\\u000a with a Wnt-specific microarray for the expression of Wnt pathway-related genes. Paired samples from uninflamed and inflamed\\u000a areas of the colon were obtained

Joann You; Anthony V. Nguyen; C. Gregory Albers; Fritz Lin; Randall F. Holcombe

2008-01-01

218

Exercise-related novel gene is involved in myoblast differentiation.  

PubMed

In this study we tried to identify new genes or proteins in skeletal muscle induced by exercise. We analyzed alterations of protein expression in mouse gastrocnemius muscles induced by swim-exercise using two dimensional gel electrophoresis and mass spectrometry. Nine spots were significantly altered between control and swim groups. One of the four protein spots whose expression was decreased was identified as functionally unknown "expressed sequence AI854635" gene. The AI854635 gene has C2H2 type zinc finger motif, and is considered to be a transcription factor. The mRNA of AI854635 gene was expressed in skeletal muscle, brain, kidney, and thymus. To elucidate the function of the AI854635 gene we analyzed mRNA expression levels during C2C12 myoblast differentiation. C2C12 myoblast began to form myotube around 20 h after the initiation of differentiation. The mRNA expression levels of AI854635 gene was significantly induced around 6 h and increased till 48 h, indicating a pivotal role in myoblast differentiation. Although the significance of decreased expression of AI854635 gene induced by swim-exercise is not clear, we found that this gene is involved in myoblast differentiation. PMID:15889621

Takahashi, Mitsuhiro; Kubota, Shunichiro

2005-04-01

219

Functional Identification of the Proteus mirabilis Core Lipopolysaccharide Biosynthesis Genes?  

PubMed Central

In this study, we report the identification of genes required for the biosynthesis of the core lipopolysaccharides (LPSs) of two strains of Proteus mirabilis. Since P. mirabilis and Klebsiella pneumoniae share a core LPS carbohydrate backbone extending up to the second outer-core residue, the functions of the common P. mirabilis genes was elucidated by genetic complementation studies using well-defined mutants of K. pneumoniae. The functions of strain-specific outer-core genes were identified by using as surrogate acceptors LPSs from two well-defined K. pneumoniae core LPS mutants. This approach allowed the identification of two new heptosyltransferases (WamA and WamC), a galactosyltransferase (WamB), and an N-acetylglucosaminyltransferase (WamD). In both strains, most of these genes were found in the so-called waa gene cluster, although one common core biosynthetic gene (wabO) was found outside this cluster.

Aquilini, Eleonora; Azevedo, Joana; Jimenez, Natalia; Bouamama, Lamiaa; Tomas, Juan M.; Regue, Miguel

2010-01-01

220

Combining evidence, biomedical literature and statistical dependence: new insights for functional annotation of gene sets  

PubMed Central

Background Large-scale genomic studies based on transcriptome technologies provide clusters of genes that need to be functionally annotated. The Gene Ontology (GO) implements a controlled vocabulary organised into three hierarchies: cellular components, molecular functions and biological processes. This terminology allows a coherent and consistent description of the knowledge about gene functions. The GO terms related to genes come primarily from semi-automatic annotations made by trained biologists (annotation based on evidence) or text-mining of the published scientific literature (literature profiling). Results We report an original functional annotation method based on a combination of evidence and literature that overcomes the weaknesses and the limitations of each approach. It relies on the Gene Ontology Annotation database (GOA Human) and the PubGene biomedical literature index. We support these annotations with statistically associated GO terms and retrieve associative relations across the three GO hierarchies to emphasise the major pathways involved by a gene cluster. Both annotation methods and associative relations were quantitatively evaluated with a reference set of 7397 genes and a multi-cluster study of 14 clusters. We also validated the biological appropriateness of our hybrid method with the annotation of a single gene (cdc2) and that of a down-regulated cluster of 37 genes identified by a transcriptome study of an in vitro enterocyte differentiation model (CaCo-2 cells). Conclusion The combination of both approaches is more informative than either separate approach: literature mining can enrich an annotation based only on evidence. Text-mining of the literature can also find valuable associated MEDLINE references that confirm the relevance of the annotation. Eventually, GO terms networks can be built with associative relations in order to highlight cooperative and competitive pathways and their connected molecular functions.

Aubry, Marc; Monnier, Annabelle; Chicault, Celine; de Tayrac, Marie; Galibert, Marie-Dominique; Burgun, Anita; Mosser, Jean

2006-01-01

221

Gene function prediction using protein domain probability and hierarchical Gene Ontology information  

Microsoft Academic Search

The Gene Ontology (GO) is a controlled vocabulary of terms to describe protein functions. It also includes a hierarchical description of the relationships among the terms in the form of a directed acyclic graph (DAG). Several systems have been developed that employ pat- tern recognition to assign gene function, using a va- riety of features, including sequence similarity, pres- ence

Jaehee Jung; Michael R. Thon

2008-01-01

222

DRUMS: a human disease related unique gene mutation search engine.  

PubMed

With the completion of the human genome project and the development of new methods for gene variant detection, the integration of mutation data and its phenotypic consequences has become more important than ever. Among all available resources, locus-specific databases (LSDBs) curate one or more specific genes' mutation data along with high-quality phenotypes. Although some genotype-phenotype data from LSDB have been integrated into central databases little effort has been made to integrate all these data by a search engine approach. In this work, we have developed disease related unique gene mutation search engine (DRUMS), a search engine for human disease related unique gene mutation as a convenient tool for biologists or physicians to retrieve gene variant and related phenotype information. Gene variant and phenotype information were stored in a gene-centred relational database. Moreover, the relationships between mutations and diseases were indexed by the uniform resource identifier from LSDB, or another central database. By querying DRUMS, users can access the most popular mutation databases under one interface. DRUMS could be treated as a domain specific search engine. By using web crawling, indexing, and searching technologies, it provides a competitively efficient interface for searching and retrieving mutation data and their relationships to diseases. The present system is freely accessible at http://www.scbit.org/glif/new/drums/index.html. PMID:21913285

Li, Zuofeng; Liu, Xingnan; Wen, Jingran; Xu, Ye; Zhao, Xin; Li, Xuan; Liu, Lei; Zhang, Xiaoyan

2011-10-01

223

The runx genes: gain or loss of function in cancer  

Microsoft Academic Search

The RUNX genes have come to prominence recently because of their roles as essential regulators of cell fate in development and their paradoxical effects in cancer, in which they can function either as tumour-suppressor genes or dominant oncogenes according to context. How can this family of transcription factors have such an ambiguous role in cancer? How and where do these

Karen Blyth; Ewan R. Cameron; James C. Neil

2005-01-01

224

Iroquois genes: genomic organization and function in vertebrate neural development  

Microsoft Academic Search

We review recent work that shows that the iroquois (Iro\\/Irx) homeobox genes have conserved genomic organization in Drosophila and vertebrates. In addition, these genes play pivotal functions in the initial specification of the vertebrate neuroectoderm, and, in collaboration with other transcription factors, later subdivision of the anterior–posterior and dorso-ventral axis of the neuroectoderm.

José Luis Gómez-Skarmeta; Juan Modolell

2002-01-01

225

Cell type specific, traceable gene silencing for functional gene analysis during vertebrate neural development  

PubMed Central

Many genes have several, sometimes divergent functions during development. Therefore, timing of gene knockdown for functional analysis during development has to be done with precise temporal control, as loss of a gene's function at early stages prevents its analysis later in development. RNAi, in combination with the accessibility of chicken embryos, is an effective approach for temporally controlled analysis of gene function during neural development. Here, we describe novel plasmid vectors that contain cell type-specific promoters/enhancers to drive the expression of a fluorescent marker, followed directly by a miR30-RNAi transcript for gene silencing. These vectors allow for direct tracing of cells experiencing gene silencing by the bright fluorescence. The level of knockdown is sufficient to reproduce the expected pathfinding defects upon perturbation of genes with known axon guidance functions. Mixing different vectors prior to electroporation enables the simultaneous knockdown of multiple genes in independent regions of the spinal cord. This permits complex cellular and molecular interactions to be examined during development, in a fast and precise manner. The advancements of the in ovo RNAi technique that we describe will not only markedly enhance functional gene analysis in the chicken, but also could be adapted to other organisms in developmental studies.

Wilson, Nicole H.; Stoeckli, Esther T.

2011-01-01

226

Evolutionary analyses of hedgehog and Hoxd-10 genes in fish species closely related to the zebrafish  

PubMed Central

The study of development has relied primarily on the isolation of mutations in genes with specific functions in development and on the comparison of their expression patterns in normal and mutant phenotypes. Comparative evolutionary analyses can complement these approaches. Phylogenetic analyses of Sonic hedgehog (Shh) and Hoxd-10 genes from 18 cyprinid fish species closely related to the zebrafish provide novel insights into the functional constraints acting on Shh. Our results confirm and extend those gained from expression and crystalline structure analyses of this gene. Unexpectedly, exon 1 of Shh is found to be almost invariant even in third codon positions among these morphologically divergent species suggesting that this exon encodes for a functionally important domain of the hedgehog protein. This is surprising because the main functional domain of Shh had been thought to be that encoded by exon 2. Comparisons of Shh and Hoxd-10 gene sequences and of resulting gene trees document higher evolutionary constraints on the former than on the latter. This might be indicative of more general evolutionary patterns in networks of developmental regulatory genes interacting in a hierarchical fashion. The presence of four members of the hedgehog gene family in cyprinid fishes was documented and their homologies to known hedgehog genes in other vertebrates were established.

Zardoya, Rafael; Abouheif, Ehab; Meyer, Axel

1996-01-01

227

Gamma and Related Functions Generalized for Sequences  

ERIC Educational Resources Information Center

|Given a sequence g[subscript k] greater than 0, the "g-factorial" product [big product][superscript k] [subscript i=1] g[subscript i] is extended from integer k to real x by generalizing properties of the gamma function [Gamma](x). The Euler-Mascheroni constant [gamma] and the beta and zeta functions are also generalized. Specific examples…

Ollerton, R. L.

2008-01-01

228

Relating Functional Groups to the Periodic Table  

ERIC Educational Resources Information Center

|An introduction to organic chemistry functional groups and their ionic variants is presented. Functional groups are ordered by the position of their specific (hetero) atom in the periodic table. Lewis structures are compared with their corresponding condensed formulas. (Contains 5 tables.)|

Struyf, Jef

2009-01-01

229

Manipulation of gene function in Xenopus laevis.  

PubMed

Xenopus laevis embryos are particularly well suited to address questions requiring either knockdown or overexpression of genes in a tissue-specific fashion during vertebrate embryonic development. These manipulations are achieved by targeted injection of either antisense morpholino oligonucleotides or synthetic mRNAs, respectively, into the early embryo. Herein we offer detailed protocols describing how to design and perform these experiments successfully, as well as a brief discussion of considerations for performing a microarray analysis in this organism. PMID:21805261

Mimoto, Mizuho S; Christian, Jan L

2011-01-01

230

Identification of functional candidate genes for body composition by expression analyses and evidencing impact by association analysis and mapping  

Microsoft Academic Search

This study aims to identify hepatic genes affecting traits related to muscularity and obesity by combining expression analyses, association studies, and gene mapping. Functional candidate genes with trait-associated expression were obtained by hybridising custom made application-specific cDNA microarrays with targets of discordant sib pairs of a porcine experimental population. Out of 238 genes addressed, nine genes were regulated by the

Siriluck Ponsuksili; Eduard Murani; Karl Schellander; Manfred Schwerin; Klaus Wimmers

2005-01-01

231

Functional analyses of lissencephaly-related proteins in Dictyostelium  

Microsoft Academic Search

Lissencephaly is a severe brain developmental disease in human infants, which is usually caused by mutations in either of two genes, LIS1 and DCX. These genes encode proteins interacting with both the microtubule and the actin systems. Here, we review the implications of data on Dictyostelium LIS1 for the elucidation of LIS1 function in higher cells and emphasize the role

Irene Meyer; Oliver Kuhnert; Ralph Gräf

2011-01-01

232

Candidate Genes, Quantitative Trait Loci, and Functional Trait Evolution in Plants  

Microsoft Academic Search

Two key characteristics of the neo-Darwinian synthesis in evolutionary biology have been its emphasis on the importance of mutations of small effect (micromutationism) and the view that studies of individual gene function shed relatively little light on evolutionary processes. Recent advances in molecular biology, however, have broken down many of the barriers between functional and evolutionary inquiry, opening the door

David L. Remington; Michael D. Purugganan

2003-01-01

233

Functional microarray analysis of nitrogen and carbon cycling genes across an Antarctic latitudinal transect.  

PubMed

Soil-borne microbial communities were examined via a functional gene microarray approach across a southern polar latitudinal gradient to gain insight into the environmental factors steering soil N- and C-cycling in terrestrial Antarctic ecosystems. The abundance and diversity of functional gene families were studied for soil-borne microbial communities inhabiting a range of environments from 51 degrees S (cool temperate-Falkland Islands) to 72 degrees S (cold rock desert-Coal Nunatak). The recently designed functional gene array used contains 24,243 oligonucleotide probes and covers >10,000 genes in >150 functional groups involved in nitrogen, carbon, sulfur and phosphorus cycling, metal reduction and resistance and organic contaminant degradation (He et al. 2007). The detected N- and C-cycle genes were significantly different across different sampling locations and vegetation types. A number of significant trends were observed regarding the distribution of key gene families across the environments examined. For example, the relative detection of cellulose degradation genes was correlated with temperature, and microbial C-fixation genes were more present in plots principally lacking vegetation. With respect to the N-cycle, denitrification genes were linked to higher soil temperatures, and N2-fixation genes were linked to plots mainly vegetated by lichens. These microarray-based results were confirmed for a number of gene families using specific real-time PCR, enzymatic assays and process rate measurements. The results presented demonstrate the utility of an integrated functional gene microarray approach in detecting shifts in functional community properties in environmental samples and provide insight into the forces driving important processes of terrestrial Antarctic nutrient cycling. PMID:18043626

Yergeau, Etienne; Kang, Sanghoon; He, Zhili; Zhou, Jizhong; Kowalchuk, George A

2007-05-24

234

Combining classifiers to predict gene function in Arabidopsis thaliana using large-scale gene expression measurements  

PubMed Central

Background Arabidopsis thaliana is the model species of current plant genomic research with a genome size of 125 Mb and approximately 28,000 genes. The function of half of these genes is currently unknown. The purpose of this study is to infer gene function in Arabidopsis using machine-learning algorithms applied to large-scale gene expression data sets, with the goal of identifying genes that are potentially involved in plant response to abiotic stress. Results Using in house and publicly available data, we assembled a large set of gene expression measurements for A. thaliana. Using those genes of known function, we first evaluated and compared the ability of basic machine-learning algorithms to predict which genes respond to stress. Predictive accuracy was measured using ROC50 and precision curves derived through cross validation. To improve accuracy, we developed a method for combining these classifiers using a weighted-voting scheme. The combined classifier was then trained on genes of known function and applied to genes of unknown function, identifying genes that potentially respond to stress. Visual evidence corroborating the predictions was obtained using electronic Northern analysis. Three of the predicted genes were chosen for biological validation. Gene knockout experiments confirmed that all three are involved in a variety of stress responses. The biological analysis of one of these genes (At1g16850) is presented here, where it is shown to be necessary for the normal response to temperature and NaCl. Conclusion Supervised learning methods applied to large-scale gene expression measurements can be used to predict gene function. However, the ability of basic learning methods to predict stress response varies widely and depends heavily on how much dimensionality reduction is used. Our method of combining classifiers can improve the accuracy of such predictions – in this case, predictions of genes involved in stress response in plants – and it effectively chooses the appropriate amount of dimensionality reduction automatically. The method provides a useful means of identifying genes in A. thaliana that potentially respond to stress, and we expect it would be useful in other organisms and for other gene functions.

Lan, Hui; Carson, Rachel; Provart, Nicholas J; Bonner, Anthony J

2007-01-01

235

Diverse types of genetic variation converge on functional gene networks involved in schizophrenia  

PubMed Central

Despite the successful identification of several relevant genomic loci, the underlying molecular mechanisms of schizophrenia remain largely unclear. We developed a computational approach (NETBAG+) that allows an integrated analysis of diverse disease-related genetic data using a unified statistical framework. The application of this approach to schizophrenia-associated genetic variations, obtained using unbiased whole-genome methods, allowed us to identify several cohesive gene networks related to axon guidance, neuronal cell mobility, synaptic function and chromosomal remodeling. The genes forming the networks are highly expressed in the brain, with higher brain expression during prenatal development. The identified networks are functionally related to genes previously implicated in schizophrenia, autism and intellectual disability. A comparative analysis of copy number variants associated with autism and schizophrenia suggests that although the molecular networks implicated in these distinct disorders may be related, the mutations associated with each disease are likely to lead, at least on average, to different functional consequences.

Gilman, Sarah R; Chang, Jonathan; Xu, Bin; Bawa, Tejdeep S; Gogos, Joseph A; Karayiorgou, Maria; Vitkup, Dennis

2013-01-01

236

Gene-Network Analysis Identifies Susceptibility Genes Related to Glycobiology in Autism  

Microsoft Academic Search

The recent identification of copy-number variation in the human genome has opened up new avenues for the discovery of positional candidate genes underlying complex genetic disorders, especially in the field of psychiatric disease. One major challenge that remains is pinpointing the susceptibility genes in the multitude of disease-associated loci. This challenge may be tackled by reconstruction of functional gene-networks from

Bert van der Zwaag; Lude Franke; Martin Poot; Ron Hochstenbach; Henk A. Spierenburg; Jacob A. S. Vorstman; Emma van Daalen; Maretha V. de Jonge; Nienke E. Verbeek; Eva H. Brilstra; Ruben van't Slot; Roel A. Ophoff; Michael A. van Es; Hylke M. Blauw; Jan H. Veldink; Jacobine E. Buizer-Voskamp; Frits A. Beemer; Leonard H. van den Berg; Cisca Wijmenga; Hans Kristian Ploos van Amstel; Herman van Engeland; J. Peter H. Burbach; Wouter G. Staal; Katharina Domschke

2009-01-01

237

Metabolic functions of duplicate genes in Saccharomyces cerevisiae  

PubMed Central

The roles of duplicate genes and their contribution to the phenomenon of enzyme dispensability are a central issue in molecular and genome evolution. A comprehensive classification of the mechanisms that may have led to their preservation, however, is currently lacking. In a systems biology approach, we classify here back-up, regulatory, and gene dosage functions for the 105 duplicate gene families of Saccharomyces cerevisiae metabolism. The key tool was the reconciled genome-scale metabolic model iLL672, which was based on the older iFF708. Computational predictions of all metabolic gene knockouts were validated with the experimentally determined phenotypes of the entire singleton yeast library of 4658 mutants under five environmental conditions. iLL672 correctly identified 96%-98% and 73%-80% of the viable and lethal singleton phenotypes, respectively. Functional roles for each duplicate family were identified by integrating the iLL672-predicted in silico duplicate knockout phenotypes, genome-scale carbon-flux distributions, singleton mutant phenotypes, and network topology analysis. The results provide no evidence for a particular dominant function that maintains duplicate genes in the genome. In particular, the back-up function is not favored by evolutionary selection because duplicates do not occur more frequently in essential reactions than singleton genes. Instead of a prevailing role, multigene-encoded enzymes cover different functions. Thus, at least for metabolism, persistence of the paralog fraction in the genome can be better explained with an array of different, often overlapping functional roles.

Kuepfer, Lars; Sauer, Uwe; Blank, Lars M.

2005-01-01

238

Relating Perturbation Magnitude to Temporal Gene Expression in Biological Systems  

SciTech Connect

A method to quantitatively relate stress to response at the level of gene expression is described using Saccharomyces cerevisiae as a model organism. Stress was defined as the magnitude of perturbation and strain was defined as the magnitude of cumulative response in terms of gene expression. Expression patterns of sixty genes previously reported to be significantly impacted by osmotic shock or belonging to the high-osmotic glycerol, glycerolipid metabolism, and glycolysis pathways were determined following perturbations of increasing sodium chloride concentrations (0, 0.5, 0.7, 1.0, 1.5, and 1.4 M). Expression of these genes was quantified temporally using reverse transcriptase real time polymerase chain reaction. The magnitude of cumulative response was obtained by calculating the total moment of area of the temporal response envelope for all the 60 genes, either together or for the set of genes related to each pathway. A non-linear relationship between stress and response was observed for the range of stress studied. This study examines a quantitative approach to quantify the strain at the level of gene expression to relate stress to strain in biological systems. The approach should be generally applicable to quantitatively evaluate the response of organisms to environmental change.

Callister, Stephen J.; Parnell, John J.; Pfrender, Michael E.; Hashsham, Syed

2009-03-19

239

Functional characterization and high-throughput proteomic analysis of interrupted genes in the archaeon Sulfolobus solfataricus.  

PubMed

Sequenced genomes often reveal interrupted coding sequences that complicate the annotation process and the subsequent functional characterization of the genes. In the past, interrupted genes were generally considered to be the result of sequencing errors or pseudogenes, that is, gene remnants with little or no biological importance. However, recent lines of evidence support the hypothesis that these coding sequences can be functional; thus, it is crucial to understand whether interrupted genes are expressed in vivo. We addressed this issue by experimentally demonstrating the existence of functional disrupted genes in archaeal genomes. We discovered previously unknown disrupted genes that have interrupted homologues in distantly related species of archaea. The combination of a RT-PCR strategy with shotgun proteomics demonstrates that interrupted genes in the archaeon Sulfolobus solfataricus are expressed in vivo. In addition, the sequence of the peptides determined by LCMSMS and experiments of in vitro translation allows us to identify a gene expressed by programmed -1 frameshifting. Our findings will enable an accurate reinterpretation of archaeal interrupted genes shedding light on their function and on archaeal genome evolution. PMID:20192274

Cobucci-Ponzano, Beatrice; Guzzini, Lucia; Benelli, Dario; Londei, Paola; Perrodou, Emmanuel; Lecompte, Odile; Tran, Diem; Sun, Jun; Wei, Jing; Mathur, Eric J; Rossi, Mosč; Moracci, Marco

2010-05-01

240

Decreased Expression of Synapse-Related Genes and Loss of Synapses in Major Depressive Disorder  

PubMed Central

Previous imaging and postmortem studies have reported a reduction in brain volume and a decrease in the size and density of neurons in the dorsolateral prefrontal cortex (dlPFC, area 9) of subjects with major depressive disorder (MDD).1,2 These findings suggest that synapse number and function are decreased in dlPFC of depressed patients. However, there has been no direct evidence for synapse loss in MDD and the gene expression alterations underlying these effects have not been identified. Here we use microarray gene profiling and electron microscopic stereology to reveal decreased expression of synaptic function-related genes in dlPFC of MDD subjects and a corresponding reduction in the number of synapses. We also identify a transcriptional repressor that is increased in MDD, and that when expressed in PFC neurons is sufficient to decrease expression of synapse-related genes, cause loss of spines and dendrites, and produce depressive behavior in rodent models of depression.

Kang, H.J.; Voleti, B.; Hajszan, T.; Rajkowska, G.; Stockmeier, C.; Licznerski, P.; Lepack, A.; Majik, M.S.; Jeong, L.S.; Banasr, M.; Son, H.; Duman, R.S.

2012-01-01

241

Targeting Fungal Genes by Diced siRNAs: A Rapid Tool to Decipher Gene Function in Aspergillus nidulans  

PubMed Central

Background Gene silencing triggered by chemically synthesized small interfering RNAs (siRNAs) has become a powerful tool for deciphering gene function in many eukaryotes. However, prediction and validation of a single siRNA duplex specific to a target gene is often ineffective. RNA interference (RNAi) with synthetic siRNA suffers from lower silencing efficacy, off-target effects and is cost-intensive, especially for functional genomic studies. With the explosion of fungal genomic information, there is an increasing need to analyze gene function in a rapid manner. Therefore, studies were performed in order to investigate the efficacy of gene silencing induced by RNase III-diced-siRNAs (d-siRNA) in model filamentous fungus, Aspergillus nidulans. Methodology/Principal Findings Stable expression of heterologous reporter gene in A. nidulans eases the examination of a new RNAi-induction route. Hence, we have optimized Agrobacterium tumefaciens-mediated transformation (AMT) of A. nidulans for stable expression of sGFP gene. This study demonstrates that the reporter GFP gene stably introduced into A. nidulans can be effectively silenced by treatment of GFP-d-siRNAs. We have shown the down-regulation of two endogenous genes, AnrasA and AnrasB of A. nidulans by d-siRNAs. We have also elucidated the function of an uncharacterized Ras homolog, rasB gene, which was found to be involved in hyphal growth and development. Further, silencing potency of d-siRNA was higher as compared to synthetic siRNA duplex, targeting AnrasA. Silencing was shown to be sequence-specific, since expression profiles of other closely related Ras family genes in d-siRNA treated AnrasA and AnrasB silenced lines exhibited no change in gene expression. Conclusions/Significance We have developed and applied a fast, specific and efficient gene silencing approach for elucidating gene function in A. nidulans using d-siRNAs. We have also optimized an efficient AMT in A. nidulans, which is useful for stable integration of transgenes.

Kalleda, Natarajaswamy; Naorem, Aruna; Manchikatla, Rajam V.

2013-01-01

242

The structure of a gene co-expression network reveals biological functions underlying eQTLs.  

PubMed

What are the commonalities between genes, whose expression level is partially controlled by eQTL, especially with regard to biological functions? Moreover, how are these genes related to a phenotype of interest? These issues are particularly difficult to address when the genome annotation is incomplete, as is the case for mammalian species. Moreover, the direct link between gene expression and a phenotype of interest may be weak, and thus difficult to handle. In this framework, the use of a co-expression network has proven useful: it is a robust approach for modeling a complex system of genetic regulations, and to infer knowledge for yet unknown genes. In this article, a case study was conducted with a mammalian species. It showed that the use of a co-expression network based on partial correlation, combined with a relevant clustering of nodes, leads to an enrichment of biological functions of around 83%. Moreover, the use of a spatial statistics approach allowed us to superimpose additional information related to a phenotype; this lead to highlighting specific genes or gene clusters that are related to the network structure and the phenotype. Three main results are worth noting: first, key genes were highlighted as a potential focus for forthcoming biological experiments; second, a set of biological functions, which support a list of genes under partial eQTL control, was set up by an overview of the global structure of the gene expression network; third, pH was found correlated with gene clusters, and then with related biological functions, as a result of a spatial analysis of the network topology. PMID:23577081

Villa-Vialaneix, Nathalie; Liaubet, Laurence; Laurent, Thibault; Cherel, Pierre; Gamot, Adrien; SanCristobal, Magali

2013-04-05

243

Predicting preferential DNA vector insertion sites: implications for functional genomics and gene therapy  

PubMed Central

Viral and transposon vectors have been employed in gene therapy as well as functional genomics studies. However, the goals of gene therapy and functional genomics are entirely different; gene therapists hope to avoid altering endogenous gene expression (especially the activation of oncogenes), whereas geneticists do want to alter expression of chromosomal genes. The odds of either outcome depend on a vector's preference to integrate into genes or control regions, and these preferences vary between vectors. Here we discuss the relative strengths of DNA vectors over viral vectors, and review methods to overcome barriers to delivery inherent to DNA vectors. We also review the tendencies of several classes of retroviral and transposon vectors to target DNA sequences, genes, and genetic elements with respect to the balance between insertion preferences and oncogenic selection. Theoretically, knowing the variables that affect integration for various vectors will allow researchers to choose the vector with the most utility for their specific purposes. The three principle benefits from elucidating factors that affect preferences in integration are as follows: in gene therapy, it allows assessment of the overall risks for activating an oncogene or inactivating a tumor suppressor gene that could lead to severe adverse effects years after treatment; in genomic studies, it allows one to discern random from selected integration events; and in gene therapy as well as functional genomics, it facilitates design of vectors that are better targeted to specific sequences, which would be a significant advance in the art of transgenesis.

Hackett, Christopher S; Geurts, Aron M; Hackett, Perry B

2007-01-01

244

Predicting Gene-Regulation Functions: Lessons from Temperate Bacteriophages  

PubMed Central

Gene-regulation functions (GRF) provide a unique characteristic of a cis-regulatory module (CRM), relating the concentrations of transcription factors (input) to the promoter activities (output). The challenge is to predict GRFs from the sequence. Here we systematically consider the lysogeny-lysis CRMs of different temperate bacteriophages such as the Lactobacillus casei phage A2, Escherichia coli phages ?, and 186 and Lactococcal phage TP901-1. This study allowed explaining a recent experimental puzzle on the role of Cro protein in the lambda switch. Several general conclusions have been drawn: 1), long-range interactions, multilayer assembly and DNA looping may lead to complex GRFs that cannot be described by linear functions of binding site occupancies; 2), in general, GRFs cannot be described by the Boolean logic, whereas a three-state non-Boolean logic suffices for the studied examples; 3), studied CRMs of the intact phages seemed to have a similar GRF topology (the number of plateaus and peaks corresponding to different expression regimes); we hypothesize that functionally equivalent CRMs might have topologically equivalent GRFs for a larger class of genetic systems; and 4) within a given GRF class, a set of mechanistic-to-mathematical transformations has been identified, which allows shaping the GRF before carrying out a system-level analysis.

Teif, Vladimir B.

2010-01-01

245

Bioinformatics Tools for Predicting GPCR Gene Functions.  

PubMed

The automatic classification of GPCRs by bioinformatics methodology can provide functional information for new GPCRs in the whole 'GPCR proteome' and this information is important for the development of novel drugs. Since GPCR proteome is classified hierarchically, general ways for GPCR function prediction are based on hierarchical classification. Various computational tools have been developed to predict GPCR functions; those tools use not simple sequence searches but more powerful methods, such as alignment-free methods, statistical model methods, and machine learning methods used in protein sequence analysis, based on learning datasets. The first stage of hierarchical function prediction involves the discrimination of GPCRs from non-GPCRs and the second stage involves the classification of the predicted GPCR candidates into family, subfamily, and sub-subfamily levels. Then, further classification is performed according to their protein-protein interaction type: binding G-protein type, oligomerized partner type, etc. Those methods have achieved predictive accuracies of around 90 %. Finally, I described the future subject of research of the bioinformatics technique about functional prediction of GPCR. PMID:24158807

Suwa, Makiko

2014-01-01

246

Integrase-directed recovery of functional genes from genomic libraries  

PubMed Central

Large population sizes, rapid growth and 3.8 billion years of evolution firmly establish microorganisms as a major source of the planet's biological and genetic diversity. However, up to 99% of the microorganisms in a given environment cannot be cultured. Culture-independent methods that directly access the genetic potential of an environmental sample can unveil new proteins with diverse functions, but the sequencing of random DNA can generate enormous amounts of extraneous data. Integrons are recombination systems that accumulate open reading frames (gene cassettes), many of which code for functional proteins with enormous adaptive potential. Some integrons harbor hundreds of gene cassettes and evidence suggests that the gene cassette pool may be limitless in size. Accessing this genetic pool has been hampered since sequence-based techniques, such as hybridization or PCR, often recover only partial genes or a small subset of those present in the sample. Here, a three-plasmid genetic strategy for the sequence-independent recovery of gene cassettes from genomic libraries is described and its use by retrieving functional gene cassettes from the chromosomal integron of Vibrio vulnificus ATCC 27562 is demonstrated. By manipulating the natural activity of integrons, we can gain access to the caches of functional genes amassed by these structures.

Rowe-Magnus, Dean A.

2009-01-01

247

Monitoring Murine Skeletal Muscle Function for Muscle Gene Therapy  

PubMed Central

The primary function of skeletal muscle is to generate force. Muscle force production is compromised in various forms of acquired and/or inherited muscle diseases. An important goal of muscle gene therapy is to recover muscle strength. Genetically engineered mice and spontaneous mouse mutants are readily available for preclinical muscle gene therapy studies. In this chapter, we outlined the methods commonly used for measuring murine skeletal muscle function. These include ex vivo and in situ analysis of the contractile profile of a single intact limb muscle (the extensor digitorium longus for ex vivo assay and the tibialis anterior muscle for in situ assay), grip force analysis, and downhill treadmill exercise. Force measurement in a single muscle is extremely useful for pilot testing of new gene therapy protocols by local gene transfer. Grip force and treadmill assessments offer body-wide evaluation following systemic muscle gene therapy.

Hakim, Chady H.; Li, Dejia; Duan, Dongsheng

2011-01-01

248

Functions of the gene products of Escherichia coli.  

PubMed Central

A list of currently identified gene products of Escherichia coli is given, together with a bibliography that provides pointers to the literature on each gene product. A scheme to categorize cellular functions is used to classify the gene products of E. coli so far identified. A count shows that the numbers of genes concerned with small-molecule metabolism are on the same order as the numbers concerned with macromolecule biosynthesis and degradation. One large category is the category of tRNAs and their synthetases. Another is the category of transport elements. The categories of cell structure and cellular processes other than metabolism are smaller. Other subjects discussed are the occurrence in the E. coli genome of redundant pairs and groups of genes of identical or closely similar function, as well as variation in the degree of density of genetic information in different parts of the genome.

Riley, M

1993-01-01

249

Cortistatin modulates calcitonin gene-related peptide release from neuronal tissues of rat. Comparison with somatostatin  

Microsoft Academic Search

Cortistatin (CST) is an endogenous neuropeptide bearing strong structural and functional analogies with somatostatin (SST). Gene expression of CST and its putative receptor MrgX2 in dorsal root ganglia (DRG) neurons in man suggests the involvement of CST in pain transmission. In this study we have investigated the effects of CST and SST on calcitonin gene-related peptide (CGRP, the main neuropeptide

Alessandro Capuano; Diego Currň; Pierluigi Navarra; Giuseppe Tringali

2011-01-01

250

Sprouty genes function in suppression of prostate tumorigenesis  

PubMed Central

Expression of Sprouty genes is frequently decreased or absent in human prostate cancer, implicating them as suppressors of tumorigenesis. Here we show they function in prostate tumor suppression in the mouse. Concomitant inactivation of Spry1 and Spry2 in prostate epithelium causes ductal hyperplasia and low-grade prostatic intraepithelial neoplasia (PIN). However, when Spry1 and Spry2 loss-of-function occurs in the context of heterozygosity for a null allele of the tumor suppressor gene Pten, there is a striking increase in PIN and evidence of neoplastic invasion. Conversely, expression of a Spry2 gain-of-function transgene in Pten null prostatic epithelium suppresses the tumorigenic effects of loss of Pten function. We show that Sprouty gene loss-of-function results in hyperactive RAS/ERK1/2 signaling throughout the prostate epithelium and cooperates with heterozygosity for a Pten null allele to promote hyperactive PI3K/AKT signaling. Furthermore, Spry2 gain-of-function can suppress hyperactivation of AKT caused by the absence of PTEN. Together, these results point to a key genetic interaction between Sprouty genes and Pten in prostate tumorigenesis and provide strong evidence that Sprouty genes can function to modulate signaling via the RAS/ERK1/2 and PI3K/AKT pathways. The finding that Sprouty genes suppress tumorigenesis caused by Pten loss-of-function suggests that therapeutic approaches aimed at restoring normal feedback mechanisms triggered by receptor tyrosine kinase signaling, including Sprouty gene expression, may provide an effective strategy to delay or prevent high-grade PIN and invasive prostate cancer.

Schutzman, Jennifer L.; Martin, Gail R.

2012-01-01

251

Structure, alternative splicing and chromosomal localization of the cystatin-related epididymal spermatogenic gene.  

PubMed Central

The cystatin superfamily of cysteine protease inhibitors consists of three major families, including the stefins, cystatins and kininogens. However, the recent identification of several genes that possess sequence similarity with the cystatins but have different gene or protein structures indicates that several new cystatin families or subgroups of families might exist. We previously identified the cystatin-related epididymal spermatogenic (Cres) gene, which is related to the family 2 cystatins but exhibits highly tissue-specific expression in the reproductive tract. In the studies presented here, an analysis of gene structure as well as chromosomal mapping studies suggest that the Cres gene might represent a new subgroup within the family 2 cystatins. Although the Cres gene possesses an additional exon encoding 5' untranslated sequences, its coding exons are similar in size to the three coding exons of the cystatin family 2 genes, and the Cres exon/intron splice junctions occur in identical locations as in the cystatin C gene. Furthermore, chromosomal mapping studies show that the Cres gene co-segregates with the cystatin C gene on mouse chromosome 2. Similar to the cystatin family 2 proteins, the Cres protein possesses the type A and B disulphide loops that are necessary for cystatin folding. Interestingly, Cres protein also possesses half of a type C disulphide loop. Although probably related to the cystatin genes, the Cres gene is distinct in that its promoter contains consensus motifs typical of regulated genes. Finally, reverse transcriptase-mediated PCR studies and the identification of new Cres cDNA clones indicate that the Cres mRNA is alternatively spliced, resulting in two Cres mRNAs that might be involved in the regulation of Cres function.

Cornwall, G A; Hsia, N; Sutton, H G

1999-01-01

252

Functional genes of non-model arthropods  

Technology Transfer Automated Retrieval System (TEKTRAN)

Technology and bioinformatics facilitate studies of non-model organisms, including pest insects and insect biological control agents. A cDNA library prepared from a laboratory-reared colony of Lygus lineolaris male nymphs identified sequences that appeared to have known functions or close homologues...

253

Functional Conservation of Gsdma Cluster Genes Specifically Duplicated in the Mouse Genome  

PubMed Central

Mouse Gasdermin A3 (Gsdma3) is the causative gene for dominant skin mutations exhibiting alopecia. Mouse has two other Gsdma3-related genes, Gsdma and Gsdma2, whereas human and rat have only one related gene. To date, no skin mutation has been reported for human GSDMA and rat Gsdma as well as mouse Gsdma and Gsdma2. Therefore, it is possible that only Gsdma3 has gain-of-function type mutations to cause dominant skin phenotype. To elucidate functional divergence among the Gsdma-related genes in mice, and to infer the function of the human and rat orthologs, we examined in vivo function of mouse Gsdma by generating Gsdma knockout mice and transgenic mice that overexpress wild-type Gsdma or Gsdma harboring a point mutation (Alanine339Threonine). The Gsdma knockout mice shows no visible phenotype, indicating that Gsdma is not essential for differentiation of epidermal cells and maintenance of the hair cycle, and that Gsdma is expressed specifically both in the inner root sheath of hair follicles and in suprabasal cell layers, whereas Gsdma3 is expressed only in suprabasal layers. By contrast, both types of the transgenic mice exhibited epidermal hyperplasia resembling the Gsdma3 mutations, although the phenotype depended on the genetic background. These results indicate that the mouse Gsdma and Gsdma3 genes share common function to regulate epithelial maintenance and/or homeostasis, and suggest that the function of human GSDMA and rat Gsdma, which are orthologs of mouse Gsdma, is conserved as well.

Tanaka, Shigekazu; Mizushina, Youichi; Kato, Yoriko; Tamura, Masaru; Shiroishi, Toshihiko

2013-01-01

254

Predicting gene function by combining expression and interaction data  

Microsoft Academic Search

In this study we combined the spurious protein interac- tion data from the Database of Interacting Proteins with the recently published gene expression data of S. cerevisiae grown with limited nutrientlimitationsunderdifferentphys- ical\\/chemical conditions (Tai et al. (2)) in order to predict protein interactions and protein functions with more confi- dence. Because proteins often have multiple functional an- notations, we propose

Rogier J. P. Van Berlo; Lodewyk F. A. Wessels; S. D. C. Martes; Marcel J. T. Reinders

2005-01-01

255

Consequences of recurrent gene flow from crops to wild relatives.  

PubMed Central

Concern about gene flow from crops to wild relatives has become widespread with the increasing cultivation of transgenic crops. Possible consequences of such gene flow include genetic assimilation, wherein crop genes replace wild ones, and demographic swamping, wherein hybrids are less fertile than their wild parents, and wild populations shrink. Using mathematical models of a wild population recurrently receiving pollen from a genetically fixed crop, we find that the conditions for genetic assimilation are not stringent, and progress towards replacement can be fast, even for disfavoured crop genes. Demographic swamping and genetic drift relax the conditions for genetic assimilation and speed progress towards replacement. Genetic assimilation can involve thresholds and hysteresis, such that a small increase in immigration can lead to fixation of a disfavoured crop gene that had been maintained at a moderate frequency, even if the increase in immigration is cancelled before the gene fixes. Demographic swamping can give rise to 'migrational meltdown', such that a small increase in immigration can lead to not only fixation of a disfavoured crop gene but also drastic shrinkage of the wild population. These findings suggest that the spread of crop genes in wild populations should be monitored more closely.

Haygood, Ralph; Ives, Anthony R; Andow, David A

2003-01-01

256

Consequences of recurrent gene flow from crops to wild relatives.  

PubMed

Concern about gene flow from crops to wild relatives has become widespread with the increasing cultivation of transgenic crops. Possible consequences of such gene flow include genetic assimilation, wherein crop genes replace wild ones, and demographic swamping, wherein hybrids are less fertile than their wild parents, and wild populations shrink. Using mathematical models of a wild population recurrently receiving pollen from a genetically fixed crop, we find that the conditions for genetic assimilation are not stringent, and progress towards replacement can be fast, even for disfavoured crop genes. Demographic swamping and genetic drift relax the conditions for genetic assimilation and speed progress towards replacement. Genetic assimilation can involve thresholds and hysteresis, such that a small increase in immigration can lead to fixation of a disfavoured crop gene that had been maintained at a moderate frequency, even if the increase in immigration is cancelled before the gene fixes. Demographic swamping can give rise to 'migrational meltdown', such that a small increase in immigration can lead to not only fixation of a disfavoured crop gene but also drastic shrinkage of the wild population. These findings suggest that the spread of crop genes in wild populations should be monitored more closely. PMID:14561300

Haygood, Ralph; Ives, Anthony R; Andow, David A

2003-09-22

257

Validation of Reference Genes for the Relative Quantification of Gene Expression in Human Epicardial Adipose Tissue  

PubMed Central

Background Relative quantification is a commonly used method for assessing gene expression, however its accuracy and reliability is dependent upon the choice of an optimal endogenous control gene, and such choice cannot be made a priori. There is limited information available on suitable reference genes to be used for studies involving human epicardial adipose tissue. The objective of the current study was to evaluate and identify optimal reference genes for use in the relative quantification of gene expression in human epicardial fat depots of lean, overweight and obese subjects. Methodology/Principal Findings Some of the commonly used reference genes including 18S, ACTB, RPL27, HPRT, CYCA, GAPDH, RPLPO, POLR2A and B2M were quantified using real-time PCR analysis. The expression stability of these genes was evaluated using Genorm, Normfinder and Bestkeeper algorithms. In addition, the effect of sample size on the validation process was studied by randomly categorizing subjects in two cohorts of n?=?2 and n?=?33. Conclusions/Significance CYCA, GAPDH and RPL27 were identified as the most stable genes common to all three algorithms and both sample sizes. Their use as reference gene pairs might contribute to the enhanced robustness of relative quantification in the studies involving the human epicardial adipose tissue.

Chechi, Kanta; Gelinas, Yves; Mathieu, Patrick; Deshaies, Yves; Richard, Denis

2012-01-01

258

Functional gene array-based analysis of microbial communities in heavy metals-contaminated lake sediments.  

PubMed

Lake DePue (IL, USA) has been contaminated for > 80 years by an adjacent Zn-smelting facility. Previous work indicated that sulfate reduction increased and biomass declined as pore-water metal concentrations increased, while 16S rRNA gene profiles remained relatively stable. To better understand this phenomenon, the sediment microbial community structure and functional potential were investigated using a functional gene microarray (GeoChip) targeting > 10 000 functional genes. Nonmetric multidimensional scaling and clustering analyses showed that the overall community structure was similar across all sites based on the relative abundance of all detected genes, but some individual gene categories did show differences. A subset of sulfate reduction genes (dsr) and the most relevant metal resistance genes were more abundant than other categories and were highly correlated with metal contamination. The most significant correlations were between pore-water metal concentrations and dsr, with Zn, Cd, and Mn as the most predictive for the presence of dsr. These results suggest that metal contamination influences sediment microbial community structure and function by increasing the abundance of relevant metal-resistant and sulfate-reducing populations. These populations therefore appear to contribute significantly to the resistance and stability of the microbial communities throughout the gradient of metal contamination in Lake DePue. PMID:23710534

Kang, Sanghoon; Van Nostrand, Joy D; Gough, Heidi L; He, Zhili; Hazen, Terry C; Stahl, David A; Zhou, Jizhong

2013-07-09

259

c-kit and its related genes in spermatogonial differentiation  

PubMed Central

Spermatogenesis is the process of production of male gametes from SSCs. The SSCs are the stem cells that differentiate into male gametes in the testis. in the mean time, the Spg are remarkable for their potential multiple trans-differentiations, which make them greatly invaluable for clinical applications. However, the molecular mechanism controlling differentiation of the Spg is still not clear. Among the discovered spermatogenesis-related genes, c-kit seems to be expressed first by the Spgs thus may play a central role in switching on the differentiation process. Expression of Kit and the activation of the Kit/Kitl pathway coincide with the start of differentiation of Spgs. Several genes have been discovered to be related to the Kit/Kitl pathway. in this review, we have summarized the recent discoveries of c-kit and the Kit/Kitl pathway-related genes in the spermatogenic cells during different stages of spermatogenesis.

Zhang, Lei; Tang, Jiangjing; Haines, Christopher J; Feng, Huai L; Lai, Liangxue; Teng, Xiaoming

2011-01-01

260

Predictive screening for regulators of conserved functional gene modules (gene batteries) in mammals  

PubMed Central

Background The expression of gene batteries, genomic units of functionally linked genes which are activated by similar sets of cis- and trans-acting regulators, has been proposed as a major determinant of cell specialization in metazoans. We developed a predictive procedure to screen the mouse and human genomes and transcriptomes for cases of gene-battery-like regulation. Results In a screen that covered ~40 per cent of all annotated protein-coding genes, we identified 21 co-expressed gene clusters with statistically supported sharing of cis-regulatory sequence elements. 66 predicted cases of over-represented transcription factor binding motifs were validated against the literature and fell into three categories: (i) previously described cases of gene battery-like regulation, (ii) previously unreported cases of gene battery-like regulation with some support in a limited number of genes, and (iii) predicted cases that currently lack experimental support. The novel predictions include for example Sox 17 and RFX transcription factor binding sites that were detected in ~10% of all testis specific genes, and HNF-1 and 4 binding sites that were detected in ~30% of all kidney specific genes respectively. The results are publicly available at . Conclusion 21 co-expressed gene clusters were enriched for a total of 66 shared cis-regulatory sequence elements. A majority of these predictions represent novel cases of potential co-regulation of functionally coupled proteins. Critical technical parameters were evaluated, and the results and the methods provide a valuable resource for future experimental design.

Nelander, Sven; Larsson, Erik; Kristiansson, Erik; Mansson, Robert; Nerman, Olle; Sigvardsson, Mikael; Mostad, Petter; Lindahl, Per

2005-01-01

261

Pairs of multiplicative functions satisfying some relations.  

National Technical Information Service (NTIS)

It is proved that if f and g are complex-valued arithmetical functions such that g(2n + 1) - Af(n) yields 0 (n yields infinity), A is near 0, then either f(n) yields 0(n yields infinity), or f(n) = n(sup s), 0 (<=) Res < 1 and A -f(2), g(n) = f(n) for eve...

N. L. Bassily I. Katai

1995-01-01

262

Rapid evolution of sex-related genes in Chlamydomonas  

PubMed Central

Biological speciation ultimately results in prezygotic isolation—the inability of incipient species to mate with one another–but little is understood about the selection pressures and genetic changes that generate this outcome. The genus Chlamydomonas comprises numerous species of unicellular green algae, including numerous geographic isolates of the species C. reinhardtii. This diverse collection has allowed us to analyze the evolution of two sex-related genes: the mid gene of C. reinhardtii, which determines whether a gamete is mating-type plus or minus, and the fus1 gene, which dictates a cell surface glycoprotein utilized by C. reinhardtii plus gametes to recognize minus gametes. Low stringency Southern analyses failed to detect any fus1 homologs in other Chlamydomonas species and detected only one mid homolog, documenting that both genes have diverged extensively during the evolution of the lineage. The one mid homolog was found in C. incerta, the species in culture that is most closely related to C. reinhardtii. Its mid gene carries numerous nonsynonymous and synonymous codon changes compared with the C. reinhardtii mid gene. In contrast, very high sequence conservation of both the mid and fus1 sequences is found in natural isolates of C. reinhardtii, indicating that the genes are not free to drift within a species but do diverge dramatically between species. Striking divergence of sex determination and mate recognition genes also has been encountered in a number of other eukaryotic phyla, suggesting that unique, and as yet unidentified, selection pressures act on these classes of genes during the speciation process.

Ferris, Patrick J.; Pavlovic, Christopher; Fabry, Stefan; Goodenough, Ursula W.

1997-01-01

263

Serotonin-related gene pathways associated with undifferentiated somatoform disorder.  

PubMed

It has been suggested that serotonergic hypofunction and serotonergic pathway genes underlie the somatic symptoms of somatoform disorders. We examined a variety of serotonin-related gene polymorphisms to determine whether undifferentiated somatoform disorder is associated with specific serotonin-related gene pathways. Serotonin-related polymorphic markers were assessed using single nucleotide polymorphism (SNP) genotyping. One hundred and two patients with undifferentiated somatoform disorder and 133 healthy subjects were enrolled. The genotype and allele frequencies of tryptophan hydroxylase (TPH)1 A218C, TPH2 rs1386494, serotonin receptor 2A-T102C (5-HTR 2A-T102C), 5-HTR 2A-G1438A and serotonin transporter (5HTTLPR) gene were compared between the groups. The Hamilton Rating Scale for Depression and the somatization subscale of the Symptom Checklist-90-Revised (SCL-90-R) were used for psychological assessment. Patients with undifferentiated somatoform disorder had higher frequencies of the TPH1 C allele than healthy controls (p=0.02) but the difference was not significant after Bonferroni correction. The frequency of TPH1 genotype also did not differ significantly between the patients and the healthy controls, nor did TPH2 rs1386494, 5-HTR 2A-T102C, 5-HTR 2A-G1438A or 5HTTLPR allele and genotype frequencies differ significantly between the two groups. These findings suggest that a variety of serotonin-related gene pathways are unlikely to be definite genetic risk factors for undifferentiated somatoform disorder. Therefore, the pathogenesis of the disorder may be related to epigenetic factors, including psychosocial and cultural factors. Nonetheless, future studies need to include a larger sample of subjects and polymorphisms of more serotonin-related gene variants. PMID:21531467

Koh, Kyung Bong; Choi, Eun Hee; Lee, Young-Joon; Han, Mooyoung

2011-05-04

264

Age-related macular degeneration: Evidence of a major gene  

SciTech Connect

Age-related macular degeneration is a major cause of blindness in developing countries. It remains a very poorly understood disorder. Although environmental and genetic factors have been implicated in its pathogenesis, none have been firmly implicated. The purpose of this study was to use pedigree analysis to evaluate the possible role of a major gene as a determinant of familial aggregation. Information was collected regarding occupation, smoking, sun exposure, associated medical problems and family history. 50 probands with age-related macular degeneration (ARMD) and 39 age, race and sex-matched controls were included in the study. In the ARMD group 15/50 (30%) of probands reported a positive family history; 22 out of 222 first degree relatives over age 60 were reported to be affected. In the control groups, none of the 138 first degree relatives over age 50 had a history of ARMD. This difference is statistically significant (p = 0.0003), indicating that genetic factors may play an important role in the pathogenesis of ARMD. In the ARMD group more siblings as compared to parents (16/127 vs. 5/82) were affected. 5/50 (10%) of the ARMD probands also gave a history of a second degree relative affected with ARMD, compared to none known among the relatives of controls. Data from 50 pedigrees were analyzed by complex segregation analysis under a class A regressive logistic model using the REGD program implemented in the SAGE package. Preliminary results allow rejection of a polygenic model and suggest there is a major gene for ARMD in these families. The inheritance model most compatible with the observed familial aggregation is autosomal recessive. In conclusion, these results are suggestive of a major gene effect in the etiology of ARMD. Identification of a major gene effect is a first step to further pursue linkage analysis and to search for the gene(s) involved in the causation of ARMD.

Bhatt, S.; Warren, C.; Yang, H. [UCLA School of Medicine, Los Angeles, CA (United States)] [and others

1994-09-01

265

Functional diversity of E1A gene autoregulation among human adenoviruses.  

PubMed Central

Autoregulation of the adenovirus E1A gene involves its constitutive expression and positively and negatively regulated transcription. Dissection of this process will identify basal-level cis elements and autoregulatory targets of the E1A promoter and functional domains within the trans-acting E1A gene products. In this report, the DNA sequence of the human subgroup B adenovirus type 3 (Ad3) E1A gene is presented and compared with that of the E1A genes of similar and distantly related human adenoviruses. The cDNA forms of the Ad3 E1A gene, corresponding to two major early mRNA species, are cloned, sequenced, and subcloned into plasmid expression vectors. Cotransfections of cell cultures are performed with Ad5 or Ad3 E1A gene expression plasmids and a reporter gene under control of the Ad5 or Ad3 E1A promoter. The Ad5 and Ad3 E1A promoters are similarly repressed by either serotype's 12S cDNA gene products. The Ad3 E1A promoter responds much more strongly than the Ad5 E1A promoter to transactivation by 13S cDNA gene products. In contrast, the 13S cDNA gene of Ad5 has greater transactivation activity than that of Ad3. Experiments with missense mutations of the Ad5 E1A gene indicate that transactivation of the Ad5 E1A promoter is weak, just reversing or balancing negative autorepression. Single amino acid substitutions in the conserved, repressive functional domain 2 of the E1A gene modulate transactivating activity that is usually associated with the separate and distal conserved functional domain 3. These results suggest a strong structure-function relationship influenced by the variable sequences separating these conserved domains. Images

Cogan, J D; Jones, S N; Hall, R K; Tibbetts, C

1992-01-01

266

Genes critical for muscle development and function in Caenorhabditis elegans identified through lethal mutations  

PubMed Central

By taking advantage of a lethal phenotype characteristic of Caenorhabditis elegans embryos that fail to move, we have identified 13 genes required for muscle assembly and function and discovered a new lethal class of alleles for three previously known muscle-affecting genes. By staining mutant embryos for myosin and actin we have recognized five distinct classes of genes: mutations in four genes disrupt the assembly of thick and thin filaments into the myofilament lattice as well as the polarized location of these components to the sarcolemma. Mutations in another three genes also disrupt thick and thin filament assembly, but allow proper polarization of lattice components based on the myosin heavy chain isoform that we analyzed. Another two classes of genes are defined by mutations with principal effects on thick or thin filament assembly into the lattice, but not both. The final class includes three genes in which mutations cause relatively minor defects in lattice assembly. Failure of certain mutants to stain with antibodies to specific muscle cell antigens suggest that two genes associated with severe disruptions of myofilament lattice assembly may code for components of the basement membrane and the sarcolemma that are concentrated where dense bodies (Z- line analogs) and M-lines attach to the cell membrane. Similar evidence suggests that one of the genes associated with mild effects on lattice assembly may code for tropomyosin. Many of the newly identified genes are likely to play critical roles in muscle development and function.

1994-01-01

267

Chromosome substitution strains: gene discovery, functional analysis, and systems studies.  

PubMed

Laboratory mice are valuable in biomedical research in part because of the extraordinary diversity of genetic resources that are available for studies of complex genetic traits and as models for human biology and disease. Chromosome substitution strains (CSSs) are important in this resource portfolio because of their demonstrated use for gene discovery, genetic and epigenetic studies, functional characterizations, and systems analysis. CSSs are made by replacing a single chromosome in a host strain with the corresponding chromosome from a donor strain. A complete CSS panel involves a total of 22 engineered inbred strains, one for each of the 19 autosomes, one each for the X and Y chromosomes, and one for mitochondria. A genome survey simply involves comparing each phenotype for each of the CSSs with the phenotypes of the host strain. The CSS panels that are available for laboratory mice have been used to dissect a remarkable variety of phenotypes and to characterize an impressive array of disease models. These surveys have revealed considerable phenotypic diversity even among closely related progenitor strains, evidence for strong epistasis and for heritable epigenetic changes. Perhaps most importantly, and presumably because of their unique genetic constitution, CSSs, and congenic strains derived from them, the genetic variants underlying quantitative trait loci (QTLs) are readily identified and functionally characterized. Together these studies show that CSSs are important resource for laboratory mice. PMID:22961226

Nadeau, Joseph H; Forejt, Jiri; Takada, Toyoyuki; Shiroishi, Toshihiko

2012-09-08

268

Sarcopenia and Age-Related Endocrine Function  

PubMed Central

Sarcopenia, the age-related loss of skeletal muscle, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, and an increased risk of fall-related injuries. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, numerous targets exist for drug discovery. In this paper, we summarize the current understanding of the endocrine contribution to sarcopenia and provide an update on hormonal intervention to try to improve endocrine defects. Myostatin inhibition seems to be the most interesting strategy for attenuating sarcopenia other than resistance training with amino acid supplementation. Testosterone supplementation in large amounts and at low frequency improves muscle defects with aging but has several side effects. Although IGF-I is a potent regulator of muscle mass, its therapeutic use has not had a positive effect probably due to local IGF-I resistance. Treatment with ghrelin may ameliorate the muscle atrophy elicited by age-dependent decreases in growth hormone. Ghrelin is an interesting candidate because it is orally active, avoiding the need for injections. A more comprehensive knowledge of vitamin-D-related mechanisms is needed to utilize this nutrient to prevent sarcopenia.

Sakuma, Kunihiro; Yamaguchi, Akihiko

2012-01-01

269

Sarcopenia and age-related endocrine function.  

PubMed

Sarcopenia, the age-related loss of skeletal muscle, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, and an increased risk of fall-related injuries. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, numerous targets exist for drug discovery. In this paper, we summarize the current understanding of the endocrine contribution to sarcopenia and provide an update on hormonal intervention to try to improve endocrine defects. Myostatin inhibition seems to be the most interesting strategy for attenuating sarcopenia other than resistance training with amino acid supplementation. Testosterone supplementation in large amounts and at low frequency improves muscle defects with aging but has several side effects. Although IGF-I is a potent regulator of muscle mass, its therapeutic use has not had a positive effect probably due to local IGF-I resistance. Treatment with ghrelin may ameliorate the muscle atrophy elicited by age-dependent decreases in growth hormone. Ghrelin is an interesting candidate because it is orally active, avoiding the need for injections. A more comprehensive knowledge of vitamin-D-related mechanisms is needed to utilize this nutrient to prevent sarcopenia. PMID:22690213

Sakuma, Kunihiro; Yamaguchi, Akihiko

2012-05-28

270

Functional relations for the density-functional exchange and correlation functionals connecting functionals at three densities  

NASA Astrophysics Data System (ADS)

It is shown that the density-functional-theory exchange and correlation functionals satisfy 0=?Ehx[?N]+2Ec?[?N]-?Ehx[?N-1?]-2Ec?[?N-1?]+2?d3r'[?N-10(r)-?N-1?(r)]v0([?N];r)+?d3r'[?N-10(r)-?N-1?(r)]r·?v0([?N];r)+?d3r'?N(r)r·?vc?([?N];r)-?d3r'?N-1?(r)r·?vc?([?N-1?];r)-?d3r'f?(r)r·?vhxc?([?N];r)-2?d3r'f?(r)vhxc?([?N];r). In the derivation of this equation the adiabatic connection formulation is used, where the ground-state density of an N-electron system ?N is kept constant independent of the electron-electron coupling strength ?. Here Ehx[?] is the Hartree plus exchange energy, Ec?[?] is the correlation energy, vhxc?[?] is the Hartree plus exchange-correlation potential, vc[?] is the correlation potential, and v0[?]is the Kohn-Sham potential. The charge densities ?N and ?N-1? are the N- and (N-1)-electron ground-state densities of the same Hamiltonian at electron-electron coupling strength ?. f?(r)=?N(r)-?N-1?(r) is the Fukui function. This equation can be useful in testing the internal self-consistency of approximations to the exchange and correlation functionals. As an example the identity is tested on the analytical Hooke's atom charge density for some frequently used approximate functionals.

Joubert, Daniel P.

2012-03-01

271

Age-related gene expression in Tourette syndrome  

PubMed Central

Because infection and immune responses have been implicated in the pathogenesis of Tourette Syndrome (TS), we hypothesized that children with TS would have altered gene expression in blood compared to controls. In addition, because TS symptoms in childhood vary with age, we tested whether gene expression changes that occur with age in TS differ from normal control children. Whole blood was obtained from 30 children and adolescents with TS and 28 healthy children and adolescents matched for age, race and gender. Gene expression (RNA) was assessed using whole genome Affymetrix microarrays. Age was analyzed as a continuous covariate and also stratified into three groups: 5-9 (common age for tic onset), 10-12 (when tics often peak), and 13-16 (tics may begin to wane). No global differences were found between TS and controls. However, expression of many genes and multiple pathways differed between TS and controls within each age group (5-9, 10-12, and 13-16), including genes involved in the immune-synapse, and proteasome- and ubiquitin- mediated proteolysis pathways. Notably, across age strata, expression of interferon response, viral processing, Natural Killer and cytotoxic T-lymphocyte cell genes differed. Our findings suggest age-related interferon, immune and protein degradation gene expression differences between TS and controls.

Lit, Lisa; Enstrom, Amanda; Sharp, Frank R; Gilbert, Donald L

2009-01-01

272

Functional Homology of Chemotaxis Genes Escherichia coli and Salmonella typhimurium  

Microsoft Academic Search

Generally nonchemotactic mutants of Escherichia coli and Salmonella typhi- murium were analyzed by interspecies complementation tests to determine the functional correspondence between the che genes of these two organisms. The E. coli che region was introduced into Salnonella recipients by means of a series of F-prime elements. Wild-type che genes of E. coli F'420 complemented all che mutants of Sabnonella

Anthony L. Defranco; JOHN S. PARKINSON; D. E. KOSHLAND

1979-01-01

273

Functions of rol genes in plant secondary metabolism  

Microsoft Academic Search

For a long time, the Agrobacterium rhizogenes rolA, rolB and rolC oncogenes have been considered to be modulators of plant growth and cell differentiation. A new function of the rol genes in plant–Agrobacterium interaction became apparent with the discovery that these genes are potential activators of secondary metabolism in transformed cells from the Solanaceae, Araliaceae, Rubiaceae, Vitaceae and Rosaceae families.

Victor P. Bulgakov

2008-01-01

274

Functional analysis of NLP genes from Botrytis elliptica  

Microsoft Academic Search

We functionally analysed two Nep1-like protein (NLP) genes from Botrytis elliptica (a specialized pathogen of lily), encoding proteins homologous to the necrosis and ethylene-inducing protein (NEP1) from Fusarium oxysporum. Single gene replacement mutants were made for BeNEP1 and BeNEP2, providing the first example of transformation and successful targeted mutagenesis in this fungus. The virulence of both mutants on lily leaves

MARTIJN STAATS; PETER VAN BAARLEN; ALEXANDER SCHOUTEN; Kan van J. A. L

2007-01-01

275

Association study of cholesterol-related genes in Alzheimer's disease.  

PubMed

Alzheimer's disease (AD) is a genetically complex disorder, and several genes related to cholesterol metabolism have been reported to contribute to AD risk. To identify further AD susceptibility genes, we have screened genes that map to chromosomal regions with high logarithm of the odds scores for AD in full genome scans and are related to cholesterol metabolism. In a European screening sample of 115 sporadic AD patients and 191 healthy control subjects, we analyzed single nucleotide polymorphisms in 28 cholesterol-related genes for association with AD. The genes HMGCS2, FDPS, RAFTLIN, ACAD8, NPC2, and ABCG1 were associated with AD at a significance level of P < or = 0.05 in this sample. Replication trials in five independent European samples detected associations of variants within HMGCS2, FDPS, NPC2, or ABCG1 with AD in some samples (P = 0.05 to P = 0.005). We did not identify a marker that was significantly associated with AD in the pooled sample (n = 2864). Stratification of this sample revealed an APOE-dependent association of HMGCS2 with AD (P = 0.004). We conclude that genetic variants investigated in this study may be associated with a moderate modification of the risk for AD in some samples. PMID:17387528

Wollmer, M Axel; Sleegers, Kristel; Ingelsson, Martin; Zekanowski, Cezary; Brouwers, Nathalie; Maruszak, Aleksandra; Brunner, Fabienne; Huynh, Kim-Dung; Kilander, Lena; Brundin, Rose-Marie; Hedlund, Marie; Giedraitis, Vilmantas; Glaser, Anna; Engelborghs, Sebastiaan; De Deyn, Peter P; Kapaki, Elisabeth; Tsolaki, Magdalini; Daniilidou, Makrina; Molyva, Dimitra; Paraskevas, George P; Thal, Dietmar R; Barcikowska, Maria; Kuznicki, Jacek; Lannfelt, Lars; Van Broeckhoven, Christine; Nitsch, Roger M; Hock, Christoph; Papassotiropoulos, Andreas

2007-03-27

276

The ERCC6 Gene and Age-Related Macular Degeneration  

PubMed Central

Background Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the developed countries and is caused by both environmental and genetic factors. A recent study (Tuo et al., PNAS) reported an association between AMD and a single nucleotide polymorphism (SNP) (rs3793784) in the ERCC6 (NM_000124) gene. The risk allele also increased ERCC6 expression. ERCC6 is involved in DNA repair and mutations in ERCC6 cause Cockayne syndrome (CS). Amongst others, photosensitivity and pigmentary retinopathy are hallmarks of CS. Methodology/Principal Findings Separate and combined data from three large AMD case-control studies and a prospective population-based study (The Rotterdam Study) were used to analyse the genetic association between ERCC6 and AMD (2682 AMD cases and 3152 controls). We also measured ERCC6 mRNA levels in retinal pigment epithelium (RPE) cells of healthy and early AMD affected human donor eyes. Rs3793784 conferred a small increase in risk for late AMD in the Dutch population (The Rotterdam and AMRO-NL study), but this was not replicated in two non-European studies (AREDS, Columbia University). In addition, the AMRO-NL study revealed no significant association for 9 other variants spanning ERCC6. Finally, we determined that ERCC6 expression in the human RPE did not depend on rs3793784 genotype, but, interestingly, on AMD status: Early AMD-affected donor eyes had a 50% lower ERCC6 expression than healthy donor eyes (P?=?0.018). Conclusions/Significance Our meta-analysis of four Caucasian cohorts does not replicate the reported association between SNPs in ERCC6 and AMD. Nevertheless, our findings on ERCC6 expression in the RPE suggest that ERCC6 may be functionally involved in AMD. Combining our data with those of the literature, we hypothesize that the AMD-related reduced transcriptional activity of ERCC6 may be caused by diverse, small and heterogeneous genetic and/or environmental determinants.

Bergeron-Sawitzke, Julie; Uitterlinden, Andre G.; Hofman, Albert; van Duijn, Cornelia M.; Merriam, Joanna E.; Smith, R. Theodore; Barile, Gaetano R.; ten Brink, Jacoline B.; Vingerling, Johannes R.; Klaver, Caroline C. W.; Allikmets, Rando; Dean, Michael; Bergen, Arthur A. B.

2010-01-01

277

Symbiosis-related pea genes modulate fungal and plant gene expression during the arbuscule stage of mycorrhiza with Glomus intraradices  

Microsoft Academic Search

The arbuscular mycorrhiza association results from a successful interaction between genomes of the plant and fungal symbiotic\\u000a partners. In this study, we analyzed the effect of inactivation of late-stage symbiosis-related pea genes on symbiosis-associated\\u000a fungal and plant molecular responses in order to gain insight into their role in the functional mycorrhizal association. The\\u000a expression of a subset of ten fungal

Elena Kuznetsova; Pascale M. A. Seddas-Dozolme; Christine Arnould; Marie Tollot; Diederik van Tuinen; Alexey Borisov; Silvio Gianinazzi; Vivienne Gianinazzi-Pearson

2010-01-01

278

Identification of programmed cell death related genes in bamboo.  

PubMed

The event of bamboo flowering and subsequent death of bamboo cells, a rare phenomenon is an interesting model to study gene expression/function in the context of the programmed cell death (PCD) in plant. To identify genes involved in autolytic cell death in bamboo (Bambusa arundinacea/Bambusa bambos Voss), a suppressive subtractive cDNA hybridization (SSH) was performed between cDNA isolated from control (healthy), as driver and test internodal tissue (45days after setting of seeds), as tester. In-silico data revealed that 82% of total ESTs (231) were non-significant (unidentified proteins) while remaining ESTs were classified as protein with known/predicted function/s. Among these, net distribution and differential expression patterns of 11 important B. arundinacea PCD specific ESTs were studied using RNA slot-blot, qRT-PCR and semi-quantitative RT. In-situ localization of mRNA-transcripts for selected bamboo PCD-specific ESTs namely V2Ba48 (Aldehyde dehydrogenase 2) and V2Ba19 (Glycogen phosphorylase) were detected using digoxigenin-labeled corresponding anti-sense RNA probes employing Confocal Laser Scanning Microscope (CLSM). Differential expression-kinetics of the aforementioned genes were confirmed during the progress of PCD after setting of seeds. Global appearance of V2Ba48, V2Ba19, V2Ba95 (Ubiquitin thioesterase) and V2Ba89 (Nebulin isoform 2) genes were identified in monocot (Oryza sativa) and dicots (Arabidopsis thaliana and Nicotiana tabacum). This is the first report on systematic analysis of genes involved in death of bamboo cells that may provide critical information regarding key metabolic/regulatory genes involved in plant PCD. PMID:22326529

Rai, Vineeta; Dey, Nrisingha

2012-02-04

279

Functional specificity among ribosomal proteins regulates gene expression.  

PubMed

Duplicated genes escape gene loss by conferring a dosage benefit or evolving diverged functions. The yeast Saccharomyces cerevisiae contains many duplicated genes encoding ribosomal proteins. Prior studies have suggested that these duplicated proteins are functionally redundant and affect cellular processes in proportion to their expression. In contrast, through studies of ASH1 mRNA in yeast, we demonstrate paralog-specific requirements for the translation of localized mRNAs. Intriguingly, these paralog-specific effects are limited to a distinct subset of duplicated ribosomal proteins. Moreover, transcriptional and phenotypic profiling of cells lacking specific ribosomal proteins reveals differences between the functional roles of ribosomal protein paralogs that extend beyond effects on mRNA localization. Finally, we show that ribosomal protein paralogs exhibit differential requirements for assembly and localization. Together, our data indicate complex specialization of ribosomal proteins for specific cellular processes and support the existence of a ribosomal code. PMID:17981122

Komili, Suzanne; Farny, Natalie G; Roth, Frederick P; Silver, Pamela A

2007-11-01

280

Neural Network Modeling of the Head-Related Transfer Function.  

National Technical Information Service (NTIS)

Battlefield synthesis of 3-D audio may require the interpolation and compression of head-related transfer function (HRTF) data. This thesis is an implementation of a functional model of the HRTF using artificial neural networks (ANNs), the model provides ...

D. Reinhardt

1998-01-01

281

PHYLOGENOMICS - GUIDED VALIDATION OF FUNCTION FOR CONSERVED UNKNOWN GENES  

SciTech Connect

Identifying functions for all gene products in all sequenced organisms is a central challenge of the post-genomic era. However, at least 30-50% of the proteins encoded by any given genome are of unknown function, or wrongly or vaguely annotated. Many of these 'unknown' proteins are common to prokaryotes and plants. We accordingly set out to predict and experimentally test the functions of such proteins. Our approach to functional prediction is integrative, coupling the extensive post-genomic resources available for plants with comparative genomics based on hundreds of microbial genomes, and functional genomic datasets from model microorganisms. The early phase is computer-assisted; later phases incorporate intellectual input from expert plant and microbial biochemists. The approach thus bridges the gap between automated homology-based annotations and the classical gene discovery efforts of experimentalists, and is much more powerful than purely computational approaches to identifying gene-function associations. Among Arabidopsis genes, we focused on those (2,325 in total) that (i) are unique or belong to families with no more than three members, (ii) are conserved between plants and prokaryotes, and (iii) have unknown or poorly known functions. Computer-assisted selection of promising targets for deeper analysis was based on homology .. independent characteristics associated in the SEED database with the prokaryotic members of each family, specifically gene clustering and phyletic spread, as well as availability of functional genomics data, and publications that could link candidate families to general metabolic areas, or to specific functions. In-depth comparative genomic analysis was then performed for about 500 top candidate families, which connected ~55 of them to general areas of metabolism and led to specific functional predictions for a subset of ~25 more. Twenty predicted functions were experimentally tested in at least one prokaryotic organism via reverse genetics, metabolic profiling, functional complementation, and recombinant protein biochemistry. Our approach predicted and validated functions for 10 formerly uncharacterized protein families common to plants and prokaryotes; none of these functions had previously been correctly predicted by computational methods. The functions of five more are currently being validated. Experimental testing of diverse representatives of these families combined with in silica analysis allowed accurate projection of the annotations to hundreds more sequenced genomes.

V, DE CRECY-LAGARD; D, HANSON A

2012-01-03

282

Cloning and Expression of Functional Region of BnNAC Transcription Factor Gene in Brassica napus  

Microsoft Academic Search

NAC transcription factor is a new-found and multifunctional transcription factor in plants. The purpose of the paper is to study the relative expression trends of BnNAC transcription factor gene under cold (4°C), salinity (200 mM NaCl) and abscisic acid (ABA) (100 ?M) stress in Brassica napus. The functional region of BnNAC gene was cloned through the homologous cloning method. The

Qin Song; Fukuan Zhao; Qingpeng Sun; Aizhen Yang

2011-01-01

283

Involvement of Trichoderma Trichothecenes in the Biocontrol Activity and Induction of Plant Defense-Related Genes  

PubMed Central

Trichoderma species produce trichothecenes, most notably trichodermin and harzianum A (HA), by a biosynthetic pathway in which several of the involved proteins have significant differences in functionality compared to their Fusarium orthologues. In addition, the genes encoding these proteins show a genomic organization differing from that of the Fusarium tri clusters. Here we describe the isolation of Trichoderma arundinaceum IBT 40837 transformants which have a disrupted or silenced tri4 gene, a gene encoding a cytochrome P450 monooxygenase that oxygenates trichodiene to give rise to isotrichodiol, and the effect of tri4 gene disruption and silencing on the expression of other tri genes. Our results indicate that the tri4 gene disruption resulted in a reduced antifungal activity against Botrytis cinerea and Rhizoctonia solani and also in a reduced ability to induce the expression of tomato plant defense-related genes belonging to the salicylic acid (SA) and jasmonate (JA) pathways against B. cinerea, in comparison to the wild-type strain, indicating that HA plays an important function in the sensitization of Trichoderma-pretreated plants against this fungal pathogen. Additionally, the effect of the interaction of T. arundinaceum with B. cinerea or R. solani and with tomato seedlings on the expressions of the tri genes was studied.

Malmierca, M. G.; Cardoza, R. E.; Alexander, N. J.; McCormick, S. P.; Hermosa, R.; Monte, E.

2012-01-01

284

Searching for functional gene modules with interaction component models  

PubMed Central

Background Functional gene modules and protein complexes are being sought from combinations of gene expression and protein-protein interaction data with various clustering-type methods. Central features missing from most of these methods are handling of uncertainty in both protein interaction and gene expression measurements, and in particular capability of modeling overlapping clusters. It would make sense to assume that proteins may play different roles in different functional modules, and the roles are evidenced in their interactions. Results We formulate a generative probabilistic model for protein-protein interaction links and introduce two ways for including gene expression data into the model. The model finds interaction components, which can be interpreted as overlapping clusters or functional modules. We demonstrate the performance on two data sets of yeast Saccharomyces cerevisiae. Our methods outperform a representative set of earlier models in the task of finding biologically relevant modules having enriched functional classes. Conclusions Combining protein interaction and gene expression data with a probabilistic generative model improves discovery of modules compared to approaches based on either data source alone. With a fairly simple model we can find biologically relevant modules better than with alternative methods, and in addition the modules may be inherently overlapping in the sense that different interactions may belong to different modules.

2010-01-01

285

Extending relational algebra and relational calculus with set-valued attributes and aggregate functions  

Microsoft Academic Search

In commercial network database management systems, set-valued fields and aggregate functions are commonly supported. However, the relational database model, as defined by Codd, does not include set-valued attributes or aggregate functions. Recently, Klug extended the relational model by incorporating aggregate functions and by defining relational algebra and calculus languages.In this paper, relational algebra and relational calculus database query languages (as

G. Özsoyo?lu; Z. Meral Özsoyoglu; Victor Matos

1987-01-01

286

Turning a hobby into a job: How duplicated genes find new functions  

Microsoft Academic Search

Gene duplication provides raw material for functional innovation. Recent advances have shed light on two fundamental questions regarding gene duplication: which genes tend to undergo duplication? And how does natural selection subsequently act on them? Genomic data suggest that different gene classes tend to be retained after single-gene and whole-genome duplications. We also know that functional differences between duplicate genes

Gavin C. Conant; Kenneth H. Wolfe

2008-01-01

287

Differential expression of apoptosis-related genes in the cochlea of noise-exposed rats  

PubMed Central

Exposure to intense noise induces apoptosis in hair cells in the cochlea. To identify the molecular changes associated with noise-induced apoptosis, we used quantitative real-time PCR to evaluate the changes in 84 apoptosis related genes in cochlear samples from the sensory epithelium and lateral wall. Sprague Dawley rats exposed to a continuous noise at 115 dB SPL for 2 h. The exposure caused a 40–60 dB threshold shift 4 h post-exposure that decreased to 20–30 dB 7 days post-exposure. These functional changes were associated with apoptotic markers including nuclear condensation and fragmentation and TUNEL staining. Immediately after the noise exposure, 12 genes were downregulated, whereas only one gene (Traf4) was upregulated. At 4 h post-exposure, 8 genes were upregulated; 3 (Tnrsf1a, Tnfrsf1b, Tnfrst5) belonged to the Tnfrsf family, 3 (Bir3, Mcl1 and Prok2) have anti-apoptotic properties and 1 (Gadd45a) is a target of p53. At 7 d post-exposure, all the upregulated genes returned to pre-noise levels. Interestingly, the normal control cochlea had high constitutive levels of several apoptosis-related genes. These constitutively expressed genes, together with the inducible genes, may participate in the induction of cochlear apoptotic activity.

Hu, Bo Hua; Cai, Qunfeng; Manohar, Senthilvelan; Jiang, Haiyan; Ding, Dalian; Coling, Donald E.; Zheng, Guiliang; Salvi, Richard

2009-01-01

288

Adaptive Functional Divergence Among Triplicated ?-Globin Genes in Rodents  

PubMed Central

The functional divergence of duplicated genes is thought to play an important role in the evolution of new developmental and physiological pathways, but the role of positive selection in driving this process remains controversial. The objective of this study was to test whether amino acid differences among triplicated ?-globin paralogs of the Norway rat (Rattus norvegicus) and the deer mouse (Peromyscus maniculatus) are attributable to a relaxation of purifying selection or to a history of positive selection that has adapted the gene products to new or modified physiological tasks. In each rodent species, the two paralogs at the 5?-end of the ?-globin gene cluster (HBA-T1 and HBA-T2) are evolving in concert and are therefore identical or nearly identical in sequence. However, in each case, the HBA-T1 and HBA-T2 paralogs are distinguished from the third paralog at the 3?-end of the gene cluster (HBA-T3) by multiple amino acid substitutions. An analysis of genomic sequence data from several rodent species revealed that the HBA-T3 genes of Rattus and Peromyscus originated via independent, lineage-specific duplication events. In the independently derived HBA-T3 genes of both species, a likelihood analysis based on a codon-substitution model revealed that accelerated rates of amino acid substitution are attributable to positive directional selection, not to a relaxation of purifying selection. As a result of functional divergence among the triplicated ?-globin genes in Rattus and Peromyscus, the red blood cells of both rodent species contain a mixture of functionally distinct ?-chain hemoglobin isoforms that are predicted to have different oxygen-binding affinities. In P. maniculatus, a species that is able to sustain physiological function under conditions of chronic hypoxia at high altitude, the coexpression of distinct hemoglobin isoforms with graded oxygen affinities is expected to broaden the permissible range of arterial oxygen tensions for pulmonary/tissue oxygen transport.

Storz, Jay F.; Hoffmann, Federico G.; Opazo, Juan C.; Moriyama, Hideaki

2008-01-01

289

Methylation patterns in 5' terminal regions of pluripotency-related genes in mature bovine gametes.  

PubMed

Gametogenesis is associated with DNA methylation and involves complicated and delicate gene regulation network in which stem cell marker genes exert their functions. Therefore, it is necessary to investigate DNA methylation profiles of those genes in mature gametes that have an effect on embryo development. However, to date, there are limited data available on these genes in mature gametes of bovine. Here we show methylation profiles in 5' terminal regions of five pluripotency-related genes (Oct4, Sox2, Nanog, Rex1 and Fgf4) in bovine mature gametes, based on the reasoning that the five genes harbour CpG islands in their own 5' terminal regions, which are frequently the targets of DNA methylation. The results showed that Oct4 and Fgf4 exhibited significant hypermethylation in sperm compared with that in oocytes (p < 0.01), while Sox2 and Nanog displayed relatively the same methylation levels between sperm and oocytes (p > 0.05). Additionally, Rex1 showed a relatively high methylation level in sperm than in oocytes, although no significant differences were found (p > 0.05). In conclusion, bovine mature gametes exhibited two methylation profiles in terms of the five genes, one being non-sex-specific and the other being sex-specific. PMID:20604984

Lan, Jie; Hua, Song; Yuan, Yuan; Zhan, Liping; He, Xiaoning; Zhang, Yong

2010-07-07

290

Decreased expression of B cell related genes in leukocytes of women with Parkinson's disease  

PubMed Central

Background Parkinson's disease (PD) is a complex disorder caused by genetic, environmental and age-related factors, and it is more prevalent in men. We aimed to identify differentially expressed genes in peripheral blood leukocytes (PBLs) that might be involved in PD pathogenesis. Transcriptomes of 30 female PD-patients and 29 age- and sex-matched controls were profiled using GeneChip Human Exon 1.0 ST Arrays. Samples were from unrelated Ashkenazi individuals, non-carriers of LRRK2 G2019S or GBA founder mutations. Results Differential expression was detected in 115 genes (206 exons), with over-representation of immune response annotations. Thirty genes were related to B cell functions, including the uniquely B cell-expressed IGHM and IGHD, the B cell surface molecules CD19, CD22 and CD79A, and the B cell gene regulator, PAX5. Quantitative-RT-PCR confirmation of these 6 genes in 79 individuals demonstrated decreased expression, mainly in women patients, independent of PD-pharmacotherapy status. Conclusions Our results suggest that the down regulation of genes related to B cell activity reflect the involvement of these cells in PD in Ashkenazi individuals and represents a molecular aspect of gender-specificity in PD.

2011-01-01

291

Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development  

PubMed Central

SUMMARY Genome-wide association studies (GWAS) have revealed numerous associations between many phenotypes and gene candidates. Frequently, however, further elucidation of gene function has not been achieved. A recent GWAS identified 69 candidate genes associated with elevated liver enzyme concentrations, which are clinical markers of liver disease. To investigate the role of these genes in liver homeostasis, we narrowed down this list to 12 genes based on zebrafish orthology, zebrafish liver expression and disease correlation. To assess the function of gene candidates during liver development, we assayed hepatic progenitors at 48 hours post fertilization (hpf) and hepatocytes at 72 hpf using in situ hybridization following morpholino knockdown in zebrafish embryos. Knockdown of three genes (pnpla3, pklr and mapk10) decreased expression of hepatic progenitor cells, whereas knockdown of eight genes (pnpla3, cpn1, trib1, fads2, slc2a2, pklr, mapk10 and samm50) decreased cell-specific hepatocyte expression. We then induced liver injury in zebrafish embryos using acetaminophen exposure and observed changes in liver toxicity incidence in morphants. Prioritization of GWAS candidates and morpholino knockdown expedites the study of newly identified genes impacting liver development and represents a feasible method for initial assessment of candidate genes to instruct further mechanistic analyses. Our analysis can be extended to GWAS for additional disease-associated phenotypes.

Liu, Leah Y.; Fox, Caroline S.; North, Trista E.; Goessling, Wolfram

2013-01-01

292

Validation and functional annotation of expression-based clusters based on gene ontology  

PubMed Central

Background The biological interpretation of large-scale gene expression data is one of the paramount challenges in current bioinformatics. In particular, placing the results in the context of other available functional genomics data, such as existing bio-ontologies, has already provided substantial improvement for detecting and categorizing genes of interest. One common approach is to look for functional annotations that are significantly enriched within a group or cluster of genes, as compared to a reference group. Results In this work, we suggest the information-theoretic concept of mutual information to investigate the relationship between groups of genes, as given by data-driven clustering, and their respective functional categories. Drawing upon related approaches (Gibbons and Roth, Genome Research 12:1574-1581, 2002), we seek to quantify to what extent individual attributes are sufficient to characterize a given group or cluster of genes. Conclusion We show that the mutual information provides a systematic framework to assess the relationship between groups or clusters of genes and their functional annotations in a quantitative way. Within this framework, the mutual information allows us to address and incorporate several important issues, such as the interdependence of functional annotations and combinatorial combinations of attributes. It thus supplements and extends the conventional search for overrepresented attributes within a group or cluster of genes. In particular taking combinations of attributes into account, the mutual information opens the way to uncover specific functional descriptions of a group of genes or clustering result. All datasets and functional annotations used in this study are publicly available. All scripts used in the analysis are provided as additional files.

Steuer, Ralf; Humburg, Peter; Selbig, Joachim

2006-01-01

293

Hearing impairment risk and interaction of folate metabolism related gene polymorphisms in an aging study  

Microsoft Academic Search

Background  Recent investigations demonstrated many genetic contributions to the development of human age-related hearing impairment (ARHI),\\u000a however, reports of factors associated with a reduction in the ARHI risk are rare. Folate metabolism is essential for cellular\\u000a functioning. Despite the extensive investigations regarding the roles of folate metabolism related gene polymorphisms in the\\u000a pathophysiology of complex diseases, such as cancer, cardio-cerebrovascular disease,

Yasue Uchida; Saiko Sugiura; Fujiko Ando; Tsutomu Nakashima; Hiroshi Shimokata

2011-01-01

294

Tissue-specific functional networks for prioritizing phenotype and disease genes.  

PubMed

Integrated analyses of functional genomics data have enormous potential for identifying phenotype-associated genes. Tissue-specificity is an important aspect of many genetic diseases, reflecting the potentially different roles of proteins and pathways in diverse cell lineages. Accounting for tissue specificity in global integration of functional genomics data is challenging, as "functionality" and "functional relationships" are often not resolved for specific tissue types. We address this challenge by generating tissue-specific functional networks, which can effectively represent the diversity of protein function for more accurate identification of phenotype-associated genes in the laboratory mouse. Specifically, we created 107 tissue-specific functional relationship networks through integration of genomic data utilizing knowledge of tissue-specific gene expression patterns. Cross-network comparison revealed significantly changed genes enriched for functions related to specific tissue development. We then utilized these tissue-specific networks to predict genes associated with different phenotypes. Our results demonstrate that prediction performance is significantly improved through using the tissue-specific networks as compared to the global functional network. We used a testis-specific functional relationship network to predict genes associated with male fertility and spermatogenesis phenotypes, and experimentally confirmed one top prediction, Mbyl1. We then focused on a less-common genetic disease, ataxia, and identified candidates uniquely predicted by the cerebellum network, which are supported by both literature and experimental evidence. Our systems-level, tissue-specific scheme advances over traditional global integration and analyses and establishes a prototype to address the tissue-specific effects of genetic perturbations, diseases and drugs. PMID:23028291

Guan, Yuanfang; Gorenshteyn, Dmitriy; Burmeister, Margit; Wong, Aaron K; Schimenti, John C; Handel, Mary Ann; Bult, Carol J; Hibbs, Matthew A; Troyanskaya, Olga G

2012-09-27

295

Tissue-Specific Functional Networks for Prioritizing Phenotype and Disease Genes  

PubMed Central

Integrated analyses of functional genomics data have enormous potential for identifying phenotype-associated genes. Tissue-specificity is an important aspect of many genetic diseases, reflecting the potentially different roles of proteins and pathways in diverse cell lineages. Accounting for tissue specificity in global integration of functional genomics data is challenging, as “functionality” and “functional relationships” are often not resolved for specific tissue types. We address this challenge by generating tissue-specific functional networks, which can effectively represent the diversity of protein function for more accurate identification of phenotype-associated genes in the laboratory mouse. Specifically, we created 107 tissue-specific functional relationship networks through integration of genomic data utilizing knowledge of tissue-specific gene expression patterns. Cross-network comparison revealed significantly changed genes enriched for functions related to specific tissue development. We then utilized these tissue-specific networks to predict genes associated with different phenotypes. Our results demonstrate that prediction performance is significantly improved through using the tissue-specific networks as compared to the global functional network. We used a testis-specific functional relationship network to predict genes associated with male fertility and spermatogenesis phenotypes, and experimentally confirmed one top prediction, Mbyl1. We then focused on a less-common genetic disease, ataxia, and identified candidates uniquely predicted by the cerebellum network, which are supported by both literature and experimental evidence. Our systems-level, tissue-specific scheme advances over traditional global integration and analyses and establishes a prototype to address the tissue-specific effects of genetic perturbations, diseases and drugs.

Guan, Yuanfang; Gorenshteyn, Dmitriy; Burmeister, Margit; Wong, Aaron K.; Schimenti, John C.; Handel, Mary Ann; Bult, Carol J.; Hibbs, Matthew A.; Troyanskaya, Olga G.

2012-01-01

296

Gene Network Analysis in a Pediatric Cohort Identifies Novel Lung Function Genes  

PubMed Central

Lung function is a heritable trait and serves as an important clinical predictor of morbidity and mortality for pulmonary conditions in adults, however, despite its importance, no studies have focused on uncovering pediatric-specific loci influencing lung function. To identify novel genetic determinants of pediatric lung function, we conducted a genome-wide association study (GWAS) of four pulmonary function traits, including FVC, FEV1, FEV1/FVC and FEF25–75% in 1556 children. Further, we carried out gene network analyses for each trait including all SNPs with a P-value of <1.0×10?3 from the individual GWAS. The GWAS identified SNPs with notable trends towards association with the pulmonary function measures, including the previously described INTS12 locus association with FEV1 (pmeta?=?1.41×10?7). The gene network analyses identified 34 networks of genes associated with pulmonary function variables in Caucasians. Of those, the glycoprotein gene network reached genome-wide significance for all four variables. P-value range pmeta?=?6.29×10?4 - 2.80×10?8 on meta-analysis. In this study, we report on specific pathways that are significantly associated with pediatric lung function at genome-wide significance. In addition, we report the first loci associated with lung function in both pediatric Caucasian and African American populations.

McDonough, Joseph M.; Wei, Zhi; Kim, Cecilia; Chiavacci, Rosetta; Mentch, Frank; Caboot, Jason B.; Spergel, Jonathan; Allen, Julian L.; Sleiman, Patrick M. A.; Hakonarson, Hakon

2013-01-01

297

New gene functions in megakaryopoiesis and platelet formation  

PubMed Central

Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.

Gieger, Christian; Radhakrishnan, Aparna; Cvejic, Ana; Tang, Weihong; Porcu, Eleonora; Pistis, Giorgio; Serbanovic-Canic, Jovana; Elling, Ulrich; Goodall, Alison H.; Labrune, Yann; Lopez, Lorna M.; Magi, Reedik; Meacham, Stuart; Okada, Yukinori; Pirastu, Nicola; Sorice, Rossella; Teumer, Alexander; Voss, Katrin; Zhang, Weihua; Ramirez-Solis, Ramiro; Bis, Joshua C.; Ellinghaus, David; Gogele, Martin; Hottenga, Jouke-Jan; Langenberg, Claudia; Kovacs, Peter; O'Reilly, Paul F.; Shin, So-Youn; Esko, Tonu; Hartiala, Jaana; Kanoni, Stavroula; Murgia, Federico; Parsa, Afshin; Stephens, Jonathan; van der Harst, Pim; van der Schoot, C. Ellen; Allayee, Hooman; Attwood, Antony; Balkau, Beverley; Bastardot, Francois; Basu, Saonli; Baumeister, Sebastian E.; Biino, Ginevra; Bomba, Lorenzo; Bonnefond, Amelie; Cambien, Francois; Chambers, John C.; Cucca, Francesco; D'Adamo, Pio; Davies, Gail; de Boer, Rudolf A.; de Geus, Eco J. C.; Doring, Angela; Elliott, Paul; Erdmann, Jeanette; Evans, David M.; Falchi, Mario; Feng, Wei; Folsom, Aaron R.; Frazer, Ian H.; Gibson, Quince D.; Glazer, Nicole L.; Hammond, Chris; Hartikainen, Anna-Liisa; Heckbert, Susan R.; Hengstenberg, Christian; Hersch, Micha; Illig, Thomas; Loos, Ruth J. F.; Jolley, Jennifer; Khaw, Kay Tee; Kuhnel, Brigitte; Kyrtsonis, Marie-Christine; Lagou, Vasiliki; Lloyd-Jones, Heather; Lumley, Thomas; Mangino, Massimo; Maschio, Andrea; Leach, Irene Mateo; McKnight, Barbara; Memari, Yasin; Mitchell, Braxton D.; Montgomery, Grant W.; Nakamura, Yusuke; Nauck, Matthias; Navis, Gerjan; Nothlings, Ute; Nolte, Ilja M.; Porteous, David J.; Pouta, Anneli; Pramstaller, Peter P.; Pullat, Janne; Ring, Susan M.; Rotter, Jerome I.; Ruggiero, Daniela; Ruokonen, Aimo; Sala, Cinzia; Samani, Nilesh J.; Sambrook, Jennifer; Schlessinger, David; Schreiber, Stefan; Schunkert, Heribert; Scott, James; Smith, Nicholas L.; Snieder, Harold; Starr, John M.; Stumvoll, Michael; Takahashi, Atsushi; Tang, W. H. Wilson; Taylor, Kent; Tenesa, Albert; Thein, Swee Lay; Tonjes, Anke; Uda, Manuela; Ulivi, Sheila; van Veldhuisen, Dirk J.; Visscher, Peter M.; Volker, Uwe; Wichmann, H.-Erich; Wiggins, Kerri L.; Willemsen, Gonneke; Yang, Tsun-Po; Zhao, Jing Hua; Zitting, Paavo; Bradley, John R.; Dedoussis, George V.; Gasparini, Paolo; Hazen, Stanley L.; Metspalu, Andres; Pirastu, Mario; Shuldiner, Alan R.; van Pelt, L. Joost; Zwaginga, Jaap-Jan; Boomsma, Dorret I.; Deary, Ian J.; Franke, Andre; Froguel, Philippe; Ganesh, Santhi K.; Jarvelin, Marjo-Riitta; Martin, Nicholas G.; Meisinger, Christa; Psaty, Bruce M.; Spector, Timothy D.; Wareham, Nicholas J.; Akkerman, Jan-Willem N.; Ciullo, Marina; Deloukas, Panos; Greinacher, Andreas; Jupe, Steve; Kamatani, Naoyuki; Khadake, Jyoti; Kooner, Jaspal S.; Penninger, Josef; Prokopenko, Inga; Stemple, Derek; Toniolo, Daniela; Wernisch, Lorenz; Sanna, Serena; Hicks, Andrew A.; Rendon, Augusto; Ferreira, Manuel A.; Ouwehand, Willem H.; Soranzo, Nicole

2012-01-01

298

Arginine functionalized peptide dendrimers as potential gene delivery vehicles.  

PubMed

The quest for highly efficient and safe gene delivery systems has become the key factor for successful application of gene therapy. Peptide dendrimers are currently investigated as excellent candidates for non-viral gene delivery vectors. In this study, we report the synthesis and characterization of arginine functionalized peptide dendrimer-based vectors ranging from 5th generation (G5A) to 6th generation (G6A) via click chemistry, and their use for gene transfection in vitro and in vivo. The dendrimers can condense plasmid DNA (pDNA) and protect pDNAs from nuclease digestion. Both atomic force microscopy (AFM) and dynamic light scattering (DLS) revealed that the sizes of dendrimer/DNA particles were within 180-250 nm range. In vitro studies showed that the functionalized peptide dendrimers provided serum independent and high transfection efficiency on all studied cells, as over 2 fold higher than that of branched polyetherimide (PEI) in the presence of serum. Dendrimer G5A with molecular weight of 17 kDa demonstrated 6-fold transfection activity than PEI in breast tumor models, as well as good biosafety proved by in vitro and in vivo toxicity evaluation. However, G6A with molecular weight of 46 kDa showed much higher cytotoxicity. The functionalized dendrimer G5A with optimal generation may be therefore a potential candidate for gene delivery vehicle. PMID:22484048

Luo, Kui; Li, Caixia; Li, Li; She, Wenchuan; Wang, Gang; Gu, Zhongwei

2012-04-07

299

Functional chitosan nanocarriers for potential applications in gene therapy  

Microsoft Academic Search

Functional chitosan nanocarriers for suicide gene therapy have been developed. Folic acid conjugated chitosan (FA-chitosan) was used to synthesize zinc sulphide quantum dots (ZnS QDs), which was further converted to chitosan nanocarriers, where the integrated FA acts as targeting, and the embedded QDs as imaging functionalities, respectively. The synthesized nanocarriers were almost spherical with sizes of ~75nm and were nontoxic

Amit Jaiswal; Arun Chattopadhyay; Siddhartha Sankar Ghosh

300

RNA-mediated gene duplication: the rat preproinsulin I gene is a functional retroposon.  

PubMed Central

Rats and mice have two, equally expressed, nonallelic genes encoding preproinsulin (genes I and II). Cytological hybridization with metaphase chromosomes indicated that both genes reside on rat chromosome I but are approximately 100,000 kilobases apart. In mice the two genes reside on two different chromosomes. DNA sequence comparisons of the gene-flanking regions in rats and mice indicated that the preproinsulin gene I has lost one of the two introns present in gene II, is flanked by a long (41-base) direct repeat, and has a remnant of a polydeoxyadenylate acid tract preceding the downstream direct repeat. These structural features indicated that gene I was generated by an RNA-mediated duplication-transposition event involving a transcript of gene II which was initiated upstream from the normal capping site. Sequence divergence analysis indicated that the pair of the original gene and its retroposed, but functional, counterpart (which appeared about 35 million years ago) is maintained by strong negative selection operating primarily on the segments encoding the chains of the mature hormone, whereas the segments encoding the parts of the polypeptide that are eliminated during processing and also the introns and the flanking regions are evolving neutrally. Images

Soares, M B; Schon, E; Henderson, A; Karathanasis, S K; Cate, R; Zeitlin, S; Chirgwin, J; Efstratiadis, A

1985-01-01

301

A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors.  

PubMed Central

The baculovirus inhibitor of apoptosis gene, iap, can impede cell death in insect cells. Here we show that iap can also prevent cell death in mammalian cells. The ability of iap to regulate programmed cell death in widely divergent species raised the possibility that cellular homologs of iap might exist. Consistent with this hypothesis, we have isolated Drosophila and human genes which encode IAP-like proteins (dILP and hILP). Like IAP, both dILP and hILP contain amino-terminal baculovirus IAP repeats (BIRs) and carboxy-terminal RING finger domains. Human ilp encodes a widely expressed cytoplasmic protein that can suppress apoptosis in transfected cells. An analysis of the expressed sequence tag database suggests that hilp is one of several human genes related to iap. Together these data suggest that iap and related cellular genes play an evolutionarily conserved role in the regulation of apoptosis. Images

Duckett, C S; Nava, V E; Gedrich, R W; Clem, R J; Van Dongen, J L; Gilfillan, M C; Shiels, H; Hardwick, J M; Thompson, C B

1996-01-01

302

Functionalized superparamagnetic nanoparticles for highly-efficient gene delivery.  

PubMed

Functionalized superparamagnetic iron oxide nanoparticles (SPIONs) can play crucial roles for medical applications such as cancer magnetic induction hyperthermia, magnetic resonance imaging, and magnetofection. Gene therapy is an emerging area of biomedicine and has the potential to revolutionize the treatment of human disease. Herein we report the results of modified magnetic nanoparticles coated with protamine containing nuclear localization signal sequences. Thermogravimetric analysis, X-ray powder diffraction, cellular uptake, and gene magnetofection efficiency of protamine modified SPIONs were evaluated. SPIONs modified with protamine resulted in more cellular uptake and higher-efficient gene transfection in HepG2 cells. The work demonstrates that protamine modified SPIONs can be used as a novel kind of highly efficient magnetic mediator for magnetic induction hyperthermia combined with gene therapy. PMID:23646508

Wang, Xiaowen; Chen, Benke; Yang, Xin; Zhang, Jieying; Zhao, Linyun; Tang, Jintian

2013-02-01

303

DAVID Knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis  

PubMed Central

Background Due to the complex and distributed nature of biological research, our current biological knowledge is spread over many redundant annotation databases maintained by many independent groups. Analysts usually need to visit many of these bioinformatics databases in order to integrate comprehensive annotation information for their genes, which becomes one of the bottlenecks, particularly for the analytic task associated with a large gene list. Thus, a highly centralized and ready-to-use gene-annotation knowledgebase is in demand for high throughput gene functional analysis. Description The DAVID Knowledgebase is built around the DAVID Gene Concept, a single-linkage method to agglomerate tens of millions of gene/protein identifiers from a variety of public genomic resources into DAVID gene clusters. The grouping of such identifiers improves the cross-reference capability, particularly across NCBI and UniProt systems, enabling more than 40 publicly available functional annotation sources to be comprehensively integrated and centralized by the DAVID gene clusters. The simple, pair-wise, text format files which make up the DAVID Knowledgebase are freely downloadable for various data analysis uses. In addition, a well organized web interface allows users to query different types of heterogeneous annotations in a high-throughput manner. Conclusion The DAVID Knowledgebase is designed to facilitate high throughput gene functional analysis. For a given gene list, it not only provides the quick accessibility to a wide range of heterogeneous annotation data in a centralized location, but also enriches the level of biological information for an individual gene. Moreover, the entire DAVID Knowledgebase is freely downloadable or searchable at .

Sherman, Brad T; Huang, Da Wei; Tan, Qina; Guo, Yongjian; Bour, Stephan; Liu, David; Stephens, Robert; Baseler, Michael W; Lane, H Clifford; Lempicki, Richard A

2007-01-01

304

Automated Discovery of Functional Generality of Human Gene Expression Programs  

Microsoft Academic Search

An important research problem in computational biology is the identification of expression programs, sets of co-expressed genes orchestrating normal or pathological processes, and the characterization of the functional breadth of these programs. The use of human expression data compendia for discovery of such programs presents several challenges including cellular inhomogeneity within samples, genetic and environmental variation across samples, uncertainty in

Georg K. Gerber; Robin D. Dowell; Tommi S. Jaakkola; David K. Gifford

2007-01-01

305

Experience report: issues in comparing gene function annotation in text  

Microsoft Academic Search

Annotating function of genes accurately is one of the most important tasks in molecular biology and medical sciences. The new sequencing technology, called the next generation sequencing technology, made sequencing the whole genomes possible with a fraction of cost of sequencing by using the traditional sequencing technology. As a result, the amount of sequence data has been growing very rapidly,

Youngik Yang; Sun Kim

2009-01-01

306

Bach2 maintains T cells in a naive state by suppressing effector memory-related genes.  

PubMed

The transcriptional repressor BTB and CNC homology 2 (Bach2) is thought to be mainly expressed in B cells with specific functions such as class switch recombination and somatic hypermutation, but its function in T cells is not known. We found equal Bach2 expression in T cells and analyzed its function using Bach2-deficient (-/-) mice. Although T-cell development was normal, numbers of peripheral naive T cells were decreased, which rapidly produced Th2 cytokines after TCR stimulation. Bach2(-/-) naive T cells highly expressed genes related to effector-memory T cells such as CCR4, ST-2 and Blimp-1. Enhanced expression of these genes induced Bach2(-/-) naive T cells to migrate toward CCR4-ligand and respond to IL33. Forced expression of Bach2 restored the expression of these genes. Using Chromatin Immunoprecipitation (ChIP)-seq analysis, we identified S100 calcium binding protein a, Heme oxigenase 1, and prolyl hydroxylase 3 as Bach2 direct target genes, which are highly expressed in effector-memory T cells. These findings indicate that Bach2 suppresses effector memory-related genes to maintain the naive T-cell state and regulates generation of effector-memory T cells. PMID:23754397

Tsukumo, Shin-ichi; Unno, Midori; Muto, Akihiko; Takeuchi, Arata; Kometani, Kohei; Kurosaki, Tomohiro; Igarashi, Kazuhiko; Saito, Takashi

2013-06-10

307

Presence and Functionality of Mating Type Genes in the Supposedly Asexual Filamentous Fungus Aspergillus oryzae  

PubMed Central

The potential for sexual reproduction in Aspergillus oryzae was assessed by investigating the presence and functionality of MAT genes. Previous genome studies had identified a MAT1-1 gene in the reference strain RIB40. We now report the existence of a complementary MAT1-2 gene and the sequencing of an idiomorphic region from A. oryzae strain AO6. This allowed the development of a PCR diagnostic assay, which detected isolates of the MAT1-1 and MAT1-2 genotypes among 180 strains assayed, including industrial tane-koji isolates. Strains used for sake and miso production showed a near-1:1 ratio of the MAT1-1 and MAT1-2 mating types, whereas strains used for soy sauce production showed a significant bias toward the MAT1-2 mating type. MAT1-1 and MAT1-2 isogenic strains were then created by genetic manipulation of the resident idiomorph, and gene expression was compared by DNA microarray and quantitative real-time PCR (qRT-PCR) methodologies under conditions in which MAT genes were expressed. Thirty-three genes were found to be upregulated more than 10-fold in either the MAT1-1 host strain or the MAT1-2 gene replacement strain relative to each other, showing that both the MAT1-1 and MAT1-2 genes functionally regulate gene expression in A. oryzae in a mating type-dependent manner, the first such report for a supposedly asexual fungus. MAT1-1 expression specifically upregulated an ?-pheromone precursor gene, but the functions of most of the genes affected were unknown. The results are consistent with a heterothallic breeding system in A. oryzae, and prospects for the discovery of a sexual cycle are discussed.

Wada, Ryuta; Maruyama, Jun-ichi; Yamaguchi, Haruka; Yamamoto, Nanase; Wagu, Yutaka; Paoletti, Mathieu; Archer, David B.; Dyer, Paul S.

2012-01-01

308

Functional Characterization of 4 Polymorphisms in Promoter Region of Hepatic Lipase Gene  

Microsoft Academic Search

Hepatic lipase (HL) is a lipolytic enzyme involved in the metabolism of plasma lipoproteins, especially high density lipoproteins. Association studies have provided strong evidence for relations of common mutations in the promoter region of the HL gene to postheparin plasma HL activity and the plasma high density lipoprotein cholesterol concentration, but the functional relevance of these polymorphisms has not been

Bjorn Lundahl; Francesca Ragogna; Fredrik Karpe; Gunilla Olivecrona; Anders Hamsten

2010-01-01

309

Altered gene expression and function of peripheral blood natural killer cells in children with autism  

Microsoft Academic Search

Immune related abnormalities have repeatedly been reported in autism spectrum disorders (ASD), including evidence of immune dysregulation and autoimmune phenomena. NK cells may play an important role in neurodevelopmental disorders such as ASD. Here we performed a gene expression screen and cellular functional analysis on peripheral blood obtained from 52 children with ASD and 27 typically developing control children enrolled

Amanda M. Enstrom; Lisa Lit; Charity E. Onore; Jeff P. Gregg; Robin L. Hansen; Isaac N. Pessah; Irva Hertz-Picciotto; Judy A. Van de Water; Frank R. Sharp; Paul Ashwood

2009-01-01

310

Evolution of the Vertebrate Paralemmin Gene Family: Ancient Origin of Gene Duplicates Suggests Distinct Functions  

PubMed Central

Paralemmin-1 is a protein implicated in plasma membrane dynamics, the development of filopodia, neurites and dendritic spines, as well as the invasiveness and metastatic potential of cancer cells. However, little is known about its mode of action, or about the biological functions of the other paralemmin isoforms: paralemmin-2, paralemmin-3 and palmdelphin. We describe here evolutionary analyses of the paralemmin gene family in a broad range of vertebrate species. Our results suggest that the four paralemmin isoform genes (PALM1, PALM2, PALM3 and PALMD) arose by quadruplication of an ancestral gene in the two early vertebrate genome duplications. Paralemmin-1 and palmdelphin were further duplicated in the teleost fish specific genome duplication. We identified a unique sequence motif common to all paralemmins, consisting of 11 highly conserved residues of which four are invariant. A single full-length paralemmin homolog with this motif was identified in the genome of the sea lamprey Petromyzon marinus and an isolated putative paralemmin motif could be detected in the genome of the lancelet Branchiostoma floridae. This allows us to conclude that the paralemmin gene family arose early and has been maintained throughout vertebrate evolution, suggesting functional diversification and specific biological roles of the paralemmin isoforms. The paralemmin genes have also maintained specific features of gene organisation and sequence. This includes the occurrence of closely linked downstream genes, initially identified as a readthrough fusion protein with mammalian paralemmin-2 (Palm2-AKAP2). We have found evidence for such an arrangement for paralemmin-1 and -2 in several vertebrate genomes, as well as for palmdelphin and paralemmin-3 in teleost fish genomes, and suggest the name paralemmin downstream genes (PDG) for this new gene family. Thus, our findings point to ancient roles for paralemmins and distinct biological functions of the gene duplicates.

Hultqvist, Greta; Ocampo Daza, Daniel; Larhammar, Dan; Kilimann, Manfred W.

2012-01-01

311

Relations among several nuclear and electronic density functional reactivity indexes  

NASA Astrophysics Data System (ADS)

An expansion of the energy functional in terms of the total number of electrons and the normal coordinates within the canonical ensemble is presented. A comparison of this expansion with the expansion of the energy in terms of the total number of electrons and the external potential leads to new relations among common density functional reactivity descriptors. The formulas obtained provide explicit links between important quantities related to the chemical reactivity of a system. In particular, the relation between the nuclear and the electronic Fukui functions is recovered. The connection between the derivatives of the electronic energy and the nuclear repulsion energy with respect to the external potential offers a proof for the ``Quantum Chemical le Chatelier Principle.'' Finally, the nuclear linear response function is defined and the relation of this function with the electronic linear response function is given.

Torrent-Sucarrat, Miquel; Luis, Josep M.; Duran, Miquel; Toro-Labbé, Alejandro; Solŕ, Miquel

2003-11-01

312

Identification of genes related to heart failure using global gene expression profiling of human failing myocardium.  

PubMed

Although various management methods have been developed for heart failure, it is necessary to investigate the diagnostic or therapeutic targets of heart failure. Accordingly, we have developed different approaches for managing heart failure by using conventional microarray analyses. We analyzed gene expression profiles of myocardial samples from 12 patients with heart failure and constructed datasets of heart failure-associated genes using clinical parameters such as pulmonary artery pressure (PAP) and ejection fraction (EF). From these 12 genes, we selected four genes with high expression levels in the heart, and examined their novelty by performing a literature-based search. In addition, we included four G-protein-coupled receptor (GPCR)-encoding genes, three enzyme-encoding genes, and one ion-channel protein-encoding gene to identify a drug target for heart failure using in silico microarray database. After the in vitro functional screening using adenovirus transfections of 12 genes into rat cardiomyocytes, we generated gene-targeting mice of five candidate genes, namely, MYLK3, GPR37L1, GPR35, MMP23, and NBC1. The results revealed that systolic blood pressure differed significantly between GPR35-KO and GPR35-WT mice as well as between GPR37L1-Tg and GPR37L1-KO mice. Further, the heart weight/body weight ratio between MYLK3-Tg and MYLK3-WT mice and between GPR37L1-Tg and GPR37L1-KO mice differed significantly. Hence, microarray analysis combined with clinical parameters can be an effective method to identify novel therapeutic targets for the prevention or management of heart failure. PMID:20100464

Min, Kyung-Duk; Asakura, Masanori; Liao, Yulin; Nakamaru, Kenji; Okazaki, Hidetoshi; Takahashi, Tomoko; Fujimoto, Kazunori; Ito, Shin; Takahashi, Ayako; Asanuma, Hiroshi; Yamazaki, Satoru; Minamino, Tetsuo; Sanada, Shoji; Seguchi, Osamu; Nakano, Atsushi; Ando, Yosuke; Otsuka, Toshiaki; Furukawa, Hidehiko; Isomura, Tadashi; Takashima, Seiji; Mochizuki, Naoki; Kitakaze, Masafumi

2010-01-25

313

Global expression analysis of nucleotide binding site-leucine rich repeat-encoding and related genes in Arabidopsis  

PubMed Central

Background Nucleotide binding site-leucine rich repeat (NBS-LRR)-encoding genes comprise the largest class of plant disease resistance genes. The 149 NBS-LRR-encoding genes and the 58 related genes that do not encode LRRs represent approximately 0.8% of all ORFs so far annotated in Arabidopsis ecotype Col-0. Despite their prevalence in the genome and functional importance, there was little information regarding expression of these genes. Results We analyzed the expression patterns of ~170 NBS-LRR-encoding and related genes in Arabidopsis Col-0 using multiple analytical approaches: expressed sequenced tag (EST) representation, massively parallel signature sequencing (MPSS), microarray analysis, rapid amplification of cDNA ends (RACE) PCR, and gene trap lines. Most of these genes were expressed at low levels with a variety of tissue specificities. Expression was detected by at least one approach for all but 10 of these genes. The expression of some but not the majority of NBS-LRR-encoding and related genes was affected by salicylic acid (SA) treatment; the response to SA varied among different accessions. An analysis of previously published microarray data indicated that ten NBS-LRR-encoding and related genes exhibited increased expression in wild-type Landsberg erecta (Ler) after flagellin treatment. Several of these ten genes also showed altered expression after SA treatment, consistent with the regulation of R gene expression during defense responses and overlap between the basal defense response and salicylic acid signaling pathways. Enhancer trap analysis indicated that neither jasmonic acid nor benzothiadiazole (BTH), a salicylic acid analog, induced detectable expression of the five NBS-LRR-encoding genes and one TIR-NBS-encoding gene tested; however, BTH did induce detectable expression of the other TIR-NBS-encoding gene analyzed. Evidence for alternative mRNA polyadenylation sites was observed for many of the tested genes. Evidence for alternative splicing was found for at least 12 genes, 11 of which encode TIR-NBS-LRR proteins. There was no obvious correlation between expression pattern, phylogenetic relationship or genomic location of the NBS-LRR-encoding and related genes studied. Conclusion Transcripts of many NBS-LRR-encoding and related genes were defined. Most were present at low levels and exhibited tissue-specific expression patterns. Expression data are consistent with most Arabidopsis NBS-LRR-encoding and related genes functioning in plant defense responses but do not preclude other biological roles.

Tan, Xiaoping; Meyers, Blake C; Kozik, Alexander; West, Marilyn AL; Morgante, Michele; St Clair, Dina A; Bent, Andrew F; Michelmore, Richard W

2007-01-01

314

GeneWeaver: a web-based system for integrative functional genomics  

PubMed Central

High-throughput genome technologies have produced a wealth of data on the association of genes and gene products to biological functions. Investigators have discovered value in combining their experimental results with published genome-wide association studies, quantitative trait locus, microarray, RNA-sequencing and mutant phenotyping studies to identify gene-function associations across diverse experiments, species, conditions, behaviors or biological processes. These experimental results are typically derived from disparate data repositories, publication supplements or reconstructions from primary data stores. This leaves bench biologists with the complex and unscalable task of integrating data by identifying and gathering relevant studies, reanalyzing primary data, unifying gene identifiers and applying ad hoc computational analysis to the integrated set. The freely available GeneWeaver (http://www.GeneWeaver.org) powered by the Ontological Discovery Environment is a curated repository of genomic experimental results with an accompanying tool set for dynamic integration of these data sets, enabling users to interactively address questions about sets of biological functions and their relations to sets of genes. Thus, large numbers of independently published genomic results can be organized into new conceptual frameworks driven by the underlying, inferred biological relationships rather than a pre-existing semantic framework. An empirical ‘ontology’ is discovered from the aggregate of experimental knowledge around user-defined areas of biological inquiry.

Bubier, Jason A.; Langston, Michael A.; Chesler, Elissa J.

2012-01-01

315

Colon cancer associated genes exhibit signatures of positive selection at functionally significant positions  

PubMed Central

Background Cancer, much like most human disease, is routinely studied by utilizing model organisms. Of these model organisms, mice are often dominant. However, our assumptions of functional equivalence fail to consider the opportunity for divergence conferred by ~180 Million Years (MY) of independent evolution between these species. For a given set of human disease related genes, it is therefore important to determine if functional equivalency has been retained between species. In this study we test the hypothesis that cancer associated genes have different patterns of substitution akin to adaptive evolution in different mammal lineages. Results Our analysis of the current literature and colon cancer databases identified 22 genes exhibiting colon cancer associated germline mutations. We identified orthologs for these 22 genes across a set of high coverage (>6X) vertebrate genomes. Analysis of these orthologous datasets revealed significant levels of positive selection. Evidence of lineage-specific positive selection was identified in 14 genes in both ancestral and extant lineages. Lineage-specific positive selection was detected in the ancestral Euarchontoglires and Hominidae lineages for STK11, in the ancestral primate lineage for CDH1, in the ancestral Murinae lineage for both SDHC and MSH6 genes and the ancestral Muridae lineage for TSC1. Conclusion Identifying positive selection in the Primate, Hominidae, Muridae and Murinae lineages suggests an ancestral functional shift in these genes between the rodent and primate lineages. Analyses such as this, combining evolutionary theory and predictions - along with medically relevant data, can thus provide us with important clues for modeling human diseases.

2012-01-01

316

Functional requirements for bacteriophage growth: gene essentiality and expression in mycobacteriophage Giles.  

PubMed

Bacteriophages represent a majority of all life forms, and the vast, dynamic population with early origins is reflected in their enormous genetic diversity. A large number of bacteriophage genomes have been sequenced. They are replete with novel genes without known relatives. We know little about their functions, which genes are required for lytic growth, and how they are expressed. Furthermore, the diversity is such that even genes with required functions - such as virion proteins and repressors - cannot always be recognized. Here we describe a functional genomic dissection of mycobacteriophage Giles, in which the virion proteins are identified, genes required for lytic growth are determined, the repressor is identified, and the transcription patterns determined. We find that although all of the predicted phage genes are expressed either in lysogeny or in lytic growth, 45% of the predicted genes are non-essential for lytic growth. We also describe genes required for DNA replication, show that recombination is required for lytic growth, and that Giles encodes a novel repressor. RNAseq analysis reveals abundant expression of a small non-coding RNA in a lysogen and in late lytic growth, although it is non-essential for lytic growth and does not alter lysogeny. PMID:23560716

Dedrick, Rebekah M; Marinelli, Laura J; Newton, Gerald L; Pogliano, Kit; Pogliano, Joseph; Hatfull, Graham F

2013-04-08

317

Application of a Novel Functional Gene Microarray to Probe the Functional Ecology of Ammonia Oxidation in Nitrifying Activated Sludge  

PubMed Central

We report on the first study trialling a newly-developed, functional gene microarray (FGA) for characterising bacterial and archaeal ammonia oxidisers in activated sludge. Mixed liquor (ML) and media biofilm samples from a full-scale integrated fixed-film activated sludge (IFAS) plant were analysed with the FGA to profile the diversity and relative abundance of ammonia-oxidising archaea and bacteria (AOA and AOB respectively). FGA analyses of AOA and AOB communities revealed ubiquitous distribution of AOA across all samples – an important finding for these newly-discovered and poorly characterised organisms. Results also revealed striking differences in the functional ecology of attached versus suspended communities within the IFAS reactor. Quantitative assessment of AOB and AOA functional gene abundance revealed a dominance of AOB in the ML and approximately equal distribution of AOA and AOB in the media-attached biofilm. Subsequent correlations of functional gene abundance data with key water quality parameters suggested an important functional role for media-attached AOB in particular for IFAS reactor nitrification performance and indicate possible functional redundancy in some IFAS ammonia oxidiser communities. Results from this investigation demonstrate the capacity of the FGA to resolve subtle ecological shifts in key microbial communities in nitrifying activated sludge and indicate its value as a tool for better understanding the linkages between the ecology and performance of these engineered systems.

Short, Michael D.; Abell, Guy C. J.; Bodrossy, Levente; van den Akker, Ben

2013-01-01

318

Prioritizing cancer-related genes with aberrant methylation based on a weighted protein-protein interaction network  

PubMed Central

Background As an important epigenetic modification, DNA methylation plays a crucial role in the development of mammals and in the occurrence of complex diseases. Genes that interact directly or indirectly may have the same or similar functions in the biological processes in which they are involved and together contribute to the related disease phenotypes. The complicated relations between genes can be clearly represented using network theory. A protein-protein interaction (PPI) network offers a platform from which to systematically identify disease-related genes from the relations between genes with similar functions. Results We constructed a weighted human PPI network (WHPN) using DNA methylation correlations based on human protein-protein interactions. WHPN represents the relationships of DNA methylation levels in gene pairs for four cancer types. A cancer-associated subnetwork (CASN) was obtained from WHPN by selecting genes associated with seed genes which were known to be methylated in the four cancers. We found that CASN had a more densely connected network community than WHPN, indicating that the genes in CASN were much closer to seed genes. We prioritized 154 potential cancer-related genes with aberrant methylation in CASN by neighborhood-weighting decision rule. A function enrichment analysis for GO and KEGG indicated that the optimized genes were mainly involved in the biological processes of regulating cell apoptosis and programmed cell death. An analysis of expression profiling data revealed that many of the optimized genes were expressed differentially in the four cancers. By examining the PubMed co-citations, we found 43 optimized genes were related with cancers and aberrant methylation, and 10 genes were validated to be methylated aberrantly in cancers. Of 154 optimized genes, 27 were as diagnostic markers and 20 as prognostic markers previously identified in literature for cancers and other complex diseases by searching PubMed manually. We found that 31 of the optimized genes were targeted as drug response markers in DrugBank. Conclusions Here we have shown that network theory combined with epigenetic characteristics provides a favorable platform from which to identify cancer-related genes. We prioritized 154 potential cancer-related genes with aberrant methylation that might contribute to the further understanding of cancers.

2011-01-01

319

[Rapid cloning and functional characterization of hypericin synthase gene].  

PubMed

Hypericin, a red-colored naphtodianthrone, is a natural product synthesized in the medicinal plant Hypericum perforatum, commonly known as St. John's wort. Hypericin has attracted a growing attention of the pharmaceutical industry because of its potential application to various therapies, including the treatment of depression and remarkable antiviral and photodynamic activities, hyp-1 gene encodes for phenolic coupling protein which catalyzes in vitro direct and specific conversion of emodin to hypericin which, however, has not formed common opinion so far. Six pairs of primers specific to hyp-1 gene were synthesized. The rapid cloning of hyp-1 gene was performed based on step-by-step extension of a short region of the gene through a series of PCR reactions. All cloned sequences were confirmed by DNA sequencing. A vector named pET32ahyp containing hyp-1 gene was constructed and was transformed into E. coli to induce heterologous expression. SDS-PAGE and Western blot results showed the recombinant Hyp-1 protein was expressed successfully in E. coli. The soluble fraction was used to test the function of the recombinant Hyp-1. Hypericin was detected by LC-MS/MS with emodin as a substrate under in vitro conditions. The above results corroborated the Hyp-1 function, a confusing question, which lay a material foundation for the synthesis of hypericin by synthetic biotechnology. PMID:22812015

Shi, Yan-Wei; Zhi, Xiao-Hui; Zheng, Hai-Na; Yang, Yan; Wang, Wei; An, Jian-Mei; Kong, Jian-Qiang

2012-05-01

320

Alcohol-related genes: contributions from studies with genetically engineered mice.  

PubMed

Since 1996, nearly 100 genes have been studied for their effects related to ethanol in mice using genetic modifications including gene deletion, gene overexpression, gene knock-in, and occasionally by studying existing mutants. Nearly all such studies have concentrated on genes expressed in brain, and the targeted genes range widely in their function, including most of the principal neurotransmitter systems, several neurohormones, and a number of signaling molecules. We review 141 published reports of effects (or lack thereof) of 93 genes on responses to ethanol. While most studies have focused on ethanol self-administration and reward, and/or sedative effects, other responses studied include locomotor stimulation, anxiolytic effects, and neuroadaptation (tolerance, sensitization, withdrawal). About 1/4 of the engineered mutations increase self-administration, 1/3 decrease it, and about 40% have no significant effect. In many cases, the effects on self-administration are rather modest and/or depend on the specific experimental procedures. In some cases, genes in the background strains on which the mutant is placed are important for results. Not surprisingly, review of the systems affected further supports roles for serotonin, gamma-aminobutyric acid, opioids and dopamine, all of which have long been foci of alcohol research. Novel modulatory effects of protein kinase C and G protein-activated inwardly rectifying K+ (GIRK) channels are also suggested. Some newer research with cannabinoid systems is promising, and has led to ongoing clinical trials. PMID:16961758

Crabbe, John C; Phillips, Tamara J; Harris, R Adron; Arends, Michael A; Koob, George F

2006-09-01

321

Comparative Functional Analysis of ZFP36 Genes during Xenopus Development  

PubMed Central

ZFP36 constitutes a small family of RNA binding proteins (formerly known as the TIS11 family) that target mRNA and promote their degradation. In mammals, ZFP36 proteins are encoded by four genes and, although they show similar activities in a cellular RNA destabilization assay, there is still a limited knowledge of their mRNA targets and it is not known whether or not they have redundant functions. In the present work, we have used the Xenopus embryo, a model system allowing gain- and loss-of-function studies, to investigate, whether individual ZFP36 proteins had distinct or redundant functions. We show that overexpression of individual amphibian zfp36 proteins leads to embryos having the same defects, with alteration in somites segmentation and pronephros formation. In these embryos, members of the Notch signalling pathway such as hairy2a or esr5 mRNA are down-regulated, suggesting common targets for the different proteins. We also show that mouse Zfp36 protein overexpression gives the same phenotype, indicating an evolutionary conserved property among ZFP36 vertebrate proteins. Morpholino oligonucleotide-induced loss-of-function leads to defects in pronephros formation, reduction in tubule size and duct coiling alterations for both zfp36 and zfp36l1, indicating no functional redundancy between these two genes. Given the conservation in gene structure and function between the amphibian and mammalian proteins and the conserved mechanisms for pronephros development, our study highlights a potential and hitherto unreported role of ZFP36 gene in kidney morphogenesis.

Treguer, Karine; Faucheux, Corinne; Veschambre, Philippe; Fedou, Sandrine; Theze, Nadine; Thiebaud, Pierre

2013-01-01

322

Comparative functional analysis of ZFP36 genes during Xenopus development.  

PubMed

ZFP36 constitutes a small family of RNA binding proteins (formerly known as the TIS11 family) that target mRNA and promote their degradation. In mammals, ZFP36 proteins are encoded by four genes and, although they show similar activities in a cellular RNA destabilization assay, there is still a limited knowledge of their mRNA targets and it is not known whether or not they have redundant functions. In the present work, we have used the Xenopus embryo, a model system allowing gain- and loss-of-function studies, to investigate, whether individual ZFP36 proteins had distinct or redundant functions. We show that overexpression of individual amphibian zfp36 proteins leads to embryos having the same defects, with alteration in somites segmentation and pronephros formation. In these embryos, members of the Notch signalling pathway such as hairy2a or esr5 mRNA are down-regulated, suggesting common targets for the different proteins. We also show that mouse Zfp36 protein overexpression gives the same phenotype, indicating an evolutionary conserved property among ZFP36 vertebrate proteins. Morpholino oligonucleotide-induced loss-of-function leads to defects in pronephros formation, reduction in tubule size and duct coiling alterations for both zfp36 and zfp36l1, indicating no functional redundancy between these two genes. Given the conservation in gene structure and function between the amphibian and mammalian proteins and the conserved mechanisms for pronephros development, our study highlights a potential and hitherto unreported role of ZFP36 gene in kidney morphogenesis. PMID:23342169

Tréguer, Karine; Faucheux, Corinne; Veschambre, Philippe; Fédou, Sandrine; Thézé, Nadine; Thiébaud, Pierre

2013-01-16

323

Identification of novel genes related to tetrodotoxin intoxication in pufferfish  

Microsoft Academic Search

To investigate the genes related to the biosynthesis or accumulation of tetrodotoxin (TTX) in pufferfish, mRNA expression patterns in the liver from pufferfish, akamefugu Takifugu chrysops and kusafugu Takifugu niphobles, were compared by mRNA arbitrarily primed reverse transcription-polymerase chain reaction (RAP RT-PCR) with fish bearing different concentrations of TTX and its derivatives. RAP RT-PCR provided a 383bp cDNA fragment and

Jeen Hee Lee; Hidehiro Kondo; Shigeru Sato; Seiji Akimoto; Toshio Saito; Masaaki Kodama; Shugo Watabe

2007-01-01

324

Evolutionary Conservation of Ceratitis capitata transformer Gene Function  

PubMed Central

Transformer functions as a binary switch gene in the sex determination and sexual differentiation of Drosophila melanogaster and Ceratitis capitata, two insect species that separated nearly 100 million years ago. The TRA protein is required for female differentiation of XX individuals, while XY individuals express smaller, presumably nonfunctional TRA peptides and consequently develop into adult males. In both species, tra confers female sexual identity through a well-conserved double-sex gene. However, unlike Drosophila tra, which is regulated by the upstream Sex-lethal gene, Ceratitis tra itself is likely to control a feedback loop that ensures the maintenance of the female sexual state. The putative CcTRA protein shares a very low degree of sequence identity with the TRA proteins from Drosophila species. However, in this study we show that a female-specific Ceratitis Cctra cDNA encoding the putative full-length CcTRA protein is able to support the female somatic and germline sexual differentiation of D. melanogaster XX; tra mutant adults. Although highly divergent, CcTRA can functionally substitute for DmTRA and induce the female-specific expression of both Dmdsx and Dmfru genes. These data demonstrate the unusual plasticity of the TRA protein that retains a conserved function despite the high evolutionary rate. We suggest that transformer plays an important role in providing a molecular basis for the variety of sex-determining systems seen among insects.

Pane, Attilio; De Simone, Annamaria; Saccone, Giuseppe; Polito, Catello

2005-01-01

325

The zebrafish genome contains two inducible, functional cyclooxygenase-2 genes  

PubMed Central

Cyclooxygenase is a key enzyme in prostanoid biosynthesis. Mammalian species have two cyclooxygenases, constitutively expressed cyclooxygenase-1 (Cox-1) and inducible cyclooxygenase-2 (Cox-2). Cox-1 and/or Cox-2 have been also identified in other vertebrates, including fish. We identified a second zebrafish Cox-2 gene orthologue, Cox-2b. All of the functionally important amino acids for cyclooxygenase enzymes are conserved in Cox-2b. The 3? untranslated region of the Cox-2b message contains AU rich elements characteristic of regulation at the level of mRNA stability. Constitutive tissue expression patterns for Cox-2a and Cox-2b are distinct, but overlap. Both Cox-2a and Cox-2b expression are inducible in the kidney when fish are exposed to tetradecanoylphorbol acetate. Like Cox-2a, Cox-2b protein, expressed in COS cells is functionally active. Thus, the zebrafish genome contains two functional, inducible Cox-2 genes. Database searching demonstrates that some fish genomes contain multiple Cox-1 or Cox-2 cyclooxygenase genes, suggesting alternate duplication and retention of this gene.

Ishikawa, Tomo-o; Griffin, Kevin J. P.; Banerjee, Utpal; Herschman, Harvey R.

2006-01-01

326

Sorghum phosphoenolpyruvate carboxylase gene family: structure, function and molecular evolution.  

PubMed

Although housekeeping functions have been shown for the phosphoenolpyruvate carboxylase (EC 4.1.1.31, PEPC) in plants and in prokaryotes, PEPC is mainly known for its specific role in the primary photosynthetic CO2 fixation in C4 and CAM plants. We have shown that in Sorghum, a monocotyledonous C4 plant, the enzyme is encoded in the nucleus by a small multigene family. Here we report the entire nucleotide sequence (7.5 kb) of the third member (CP21) that completes the structure of the Sorghum PEPC gene family. Nucleotide composition, CpG islands and GC content of the three Sorghum PEPC genes are analysed with respect to their possible implications in the regulation of expression. A study of structure/function and phylogenetic relationships based on the compilation of all PEPC sequences known so far is presented. Data demonstrated that: (1) the different forms of plant PEPC have very similar primary structures, functional and regulatory properties, (2) neither apparent amino acid sequences nor phylogenetic relationships are specific for the C4 and CAM PEPCs and (3) expression of the different genes coding for the Sorghum PEPC isoenzymes is differently regulated (i.e. by light, nitrogen source) in a spatial and temporal manner. These results suggest that the main distinguishing feature between plant PEPCs is to be found at the level of genes expression rather than in their primary structure. PMID:8443342

Lepiniec, L; Keryer, E; Philippe, H; Gadal, P; Crétin, C

1993-02-01

327

Gene Expression and Functional Annotation of the Human Ciliary Body Epithelia  

PubMed Central

Purpose The ciliary body (CB) of the human eye consists of the non-pigmented (NPE) and pigmented (PE) neuro-epithelia. We investigated the gene expression of NPE and PE, to shed light on the molecular mechanisms underlying the most important functions of the CB. We also developed molecular signatures for the NPE and PE and studied possible new clues for glaucoma. Methods We isolated NPE and PE cells from seven healthy human donor eyes using laser dissection microscopy. Next, we performed RNA isolation, amplification, labeling and hybridization against 44×k Agilent microarrays. For microarray conformations, we used a literature study, RT-PCRs, and immunohistochemical stainings. We analyzed the gene expression data with R and with the knowledge database Ingenuity. Results The gene expression profiles and functional annotations of the NPE and PE were highly similar. We found that the most important functionalities of the NPE and PE were related to developmental processes, neural nature of the tissue, endocrine and metabolic signaling, and immunological functions. In total 1576 genes differed statistically significantly between NPE and PE. From these genes, at least 3 were cell-specific for the NPE and 143 for the PE. Finally, we observed high expression in the (N)PE of 35 genes previously implicated in molecular mechanisms related to glaucoma. Conclusion Our gene expression analysis suggested that the NPE and PE of the CB were quite similar. Nonetheless, cell-type specific differences were found. The molecular machineries of the human NPE and PE are involved in a range of neuro-endocrinological, developmental and immunological functions, and perhaps glaucoma.

Janssen, Sarah F.; Gorgels, Theo G. M. F.; Bossers, Koen; ten Brink, Jacoline B.; Essing, Anke H. W.; Nagtegaal, Martijn; van der Spek, Peter J.; Jansonius, Nomdo M.; Bergen, Arthur A. B.

2012-01-01

328

Comparative genomics and functional study of lipid metabolic genes in Caenorhabditis elegans  

PubMed Central

Background Animal models are indispensable to understand the lipid metabolism and lipid metabolic diseases. Over the last decade, the nematode Caenorhabditis elegans has become a popular animal model for exploring the regulation of lipid metabolism, obesity, and obese-related diseases. However, the genomic and functional conservation of lipid metabolism from C. elegans to humans remains unknown. In the present study, we systematically analyzed genes involved in lipid metabolism in the C. elegans genome using comparative genomics. Results We built a database containing 471 lipid genes from the C. elegans genome, and then assigned most of lipid genes into 16 different lipid metabolic pathways that were integrated into a network. Over 70% of C. elegans lipid genes have human orthologs, with 237 of 471 C. elegans lipid genes being conserved in humans, mice, rats, and Drosophila, of which 71 genes are specifically related to human metabolic diseases. Moreover, RNA-mediated interference (RNAi) was used to disrupt the expression of 356 of 471 lipid genes with available RNAi clones. We found that 21 genes strongly affect fat storage, development, reproduction, and other visible phenotypes, 6 of which have not previously been implicated in the regulation of fat metabolism and other phenotypes. Conclusions This study provides the first systematic genomic insight into lipid metabolism in C. elegans, supporting the use of C. elegans as an increasingly prominent model in the study of metabolic diseases.

2013-01-01

329

Isolation of oligotrophic denitrifiers carrying previously uncharacterized functional gene sequences.  

PubMed

Oligotrophic denitrifying bacteria, including those belonging to the genera Herbaspirillum, Azospirillum, and Bradyrhizobium, were obtained using a single-cell isolation technique. The taxonomic composition of the denitrifier population was similar to those assessed by previous culture-independent studies. The sequencing of nitrite reductase and N(2)O reductase genes of these strains revealed previously unknown links between 16S rRNA and the denitrification-functional gene phylogenies. In particular, we identified Bradyrhizobium strains that harbor nirS sequences previously detected only in culture-independent studies. PMID:21075882

Ishii, Satoshi; Ashida, Naoaki; Otsuka, Shigeto; Senoo, Keishi

2010-11-12

330

Isolation of Oligotrophic Denitrifiers Carrying Previously Uncharacterized Functional Gene Sequences? †  

PubMed Central

Oligotrophic denitrifying bacteria, including those belonging to the genera Herbaspirillum, Azospirillum, and Bradyrhizobium, were obtained using a single-cell isolation technique. The taxonomic composition of the denitrifier population was similar to those assessed by previous culture-independent studies. The sequencing of nitrite reductase and N2O reductase genes of these strains revealed previously unknown links between 16S rRNA and the denitrification-functional gene phylogenies. In particular, we identified Bradyrhizobium strains that harbor nirS sequences previously detected only in culture-independent studies.

Ishii, Satoshi; Ashida, Naoaki; Otsuka, Shigeto; Senoo, Keishi

2011-01-01

331

Ascorbate peroxidase-related (APx-R) is not a duplicable gene.  

PubMed

Phylogenetic, genomic and functional analyses have allowed the identification of a new class of putative heme peroxidases, so called APx-R (APx-Related). These new class, mainly present in the green lineage (including green algae and land plants), can also be detected in other unicellular chloroplastic organisms. Except for recent polyploid organisms, only single-copy of APx-R gene was detected in each genome, suggesting that the majority of the APx-R extra-copies were lost after chromosomal or segmental duplications. In a similar way, most APx-R co-expressed genes in Arabidopsis genome do not have conserved extra-copies after chromosomal duplications and are predicted to be localized in organelles, as are the APx-R. The member of this gene network can be considered as unique gene, well conserved through the evolution due to a strong negative selection pressure and a low evolution rate. PMID:22231200

Dunand, Christophe; Mathé, Catherine; Lazzarotto, Fernanda; Margis, Rogério; Margis-Pinheiro, Marcia

2011-12-01

332

Ascorbate peroxidase-related (APx-R) is not a duplicable gene  

PubMed Central

Phylogenetic, genomic and functional analyses have allowed the identification of a new class of putative heme peroxidases, so called APx-R (APx-Related). These new class, mainly present in the green lineage (including green algae and land plants), can also be detected in other unicellular chloroplastic organisms. Except for recent polyploid organisms, only single-copy of APx-R gene was detected in each genome, suggesting that the majority of the APx-R extra-copies were lost after chromosomal or segmental duplications. In a similar way, most APx-R co-expressed genes in Arabidopsis genome do not have conserved extra-copies after chromosomal duplications and are predicted to be localized in organelles, as are the APx-R. The member of this gene network can be considered as unique gene, well conserved through the evolution due to a strong negative selection pressure and a low evolution rate.

Dunand, Christophe; Mathe, Catherine; Lazzarotto, Fernanda; Margis, Rogerio; Margis-Pinheiro, Marcia

2011-01-01

333

Age-related functional reorganization, structural changes, and preserved cognition.  

PubMed

Although healthy aging is associated with general cognitive decline, there is considerable variability in the extent to which cognitive functions decline or are preserved. Preserved cognitive function in the context of age-related neuroanatomical and functional changes, has been attributed to compensatory mechanisms. However, the existing sparse evidence is largely focused on functions associated with the frontal cortex, leaving open the question of how wider age-related brain changes relate to compensation. We evaluated relationships between age-related neural and functional changes in the context of preserved cognitive function by combining measures of structure, function, and cognitive performance during spoken language comprehension using a paradigm that does not involve an explicit task. We used a graph theoretical approach to derive cognitive activation-related functional magnetic resonance imaging networks. Correlating network properties with age, neuroanatomical variations, and behavioral data, we found that decreased gray matter integrity was associated with decreased connectivity within key language regions but increased overall functional connectivity. However, this network reorganization was less efficient, suggesting that engagement of a more distributed network in aging might be triggered by reduced connectivity within specialized networks. PMID:23942392

Meunier, David; Stamatakis, Emmanuel A; Tyler, Lorraine K

2013-08-12

334

HuMiChip: Development of a Functional Gene Array for the Study of Human Microbiomes  

SciTech Connect

Microbiomes play very important roles in terms of nutrition, health and disease by interacting with their hosts. Based on sequence data currently available in public domains, we have developed a functional gene array to monitor both organismal and functional gene profiles of normal microbiota in human and mouse hosts, and such an array is called human and mouse microbiota array, HMM-Chip. First, seed sequences were identified from KEGG databases, and used to construct a seed database (seedDB) containing 136 gene families in 19 metabolic pathways closely related to human and mouse microbiomes. Second, a mother database (motherDB) was constructed with 81 genomes of bacterial strains with 54 from gut and 27 from oral environments, and 16 metagenomes, and used for selection of genes and probe design. Gene prediction was performed by Glimmer3 for bacterial genomes, and by the Metagene program for metagenomes. In total, 228,240 and 801,599 genes were identified for bacterial genomes and metagenomes, respectively. Then the motherDB was searched against the seedDB using the HMMer program, and gene sequences in the motherDB that were highly homologous with seed sequences in the seedDB were used for probe design by the CommOligo software. Different degrees of specific probes, including gene-specific, inclusive and exclusive group-specific probes were selected. All candidate probes were checked against the motherDB and NCBI databases for specificity. Finally, 7,763 probes covering 91.2percent (12,601 out of 13,814) HMMer confirmed sequences from 75 bacterial genomes and 16 metagenomes were selected. This developed HMM-Chip is able to detect the diversity and abundance of functional genes, the gene expression of microbial communities, and potentially, the interactions of microorganisms and their hosts.

Tu, Q.; Deng, Ye; Lin, Lu; Hemme, Chris L.; He, Zhili; Zhou, Jizhong

2010-05-17

335

ETS-related Gene (ERG) Controls Endothelial Cell Permeability via Transcriptional Regulation of the Claudin 5 (CLDN5) Gene*  

PubMed Central

ETS-related gene (ERG) is a member of the ETS transcription factor family. Our previous studies have shown that ERG expression is highly enriched in endothelial cells (EC) both in vitro and in vivo. ERG expression is markedly repressed in response to inflammatory stimuli. It has been shown that ERG is a positive regulator of several EC-restricted genes including VE-cadherin, endoglin, and von Willebrand factor, and a negative regulator of other genes such as interleukin (IL)-8 and intercellular adhesion molecule (ICAM)-1. In this study we have identified a novel role for ERG in the regulation of EC barrier function. ERG knockdown results in marked increases in EC permeability. This is associated with a significant increase of stress fiber and gap formation in EC. Furthermore, we identify CLDN5 as a downstream target of ERG in EC. Thus, our results suggest that ERG plays a pivotal role in regulating EC barrier function and that this effect is mediated in part through its regulation of CLDN5 gene expression.

Yuan, Lei; Le Bras, Alexandra; Sacharidou, Anastasia; Itagaki, Kiyoshi; Zhan, Yumei; Kondo, Maiko; Carman, Christopher V.; Davis, George E.; Aird, William C.; Oettgen, Peter

2012-01-01

336

ETS-related gene (ERG) controls endothelial cell permeability via transcriptional regulation of the claudin 5 (CLDN5) gene.  

PubMed

ETS-related gene (ERG) is a member of the ETS transcription factor family. Our previous studies have shown that ERG expression is highly enriched in endothelial cells (EC) both in vitro and in vivo. ERG expression is markedly repressed in response to inflammatory stimuli. It has been shown that ERG is a positive regulator of several EC-restricted genes including VE-cadherin, endoglin, and von Willebrand factor, and a negative regulator of other genes such as interleukin (IL)-8 and intercellular adhesion molecule (ICAM)-1. In this study we have identified a novel role for ERG in the regulation of EC barrier function. ERG knockdown results in marked increases in EC permeability. This is associated with a significant increase of stress fiber and gap formation in EC. Furthermore, we identify CLDN5 as a downstream target of ERG in EC. Thus, our results suggest that ERG plays a pivotal role in regulating EC barrier function and that this effect is mediated in part through its regulation of CLDN5 gene expression. PMID:22235125

Yuan, Lei; Le Bras, Alexandra; Sacharidou, Anastasia; Itagaki, Kiyoshi; Zhan, Yumei; Kondo, Maiko; Carman, Christopher V; Davis, George E; Aird, William C; Oettgen, Peter

2012-01-10

337

Globin gene expression in correlation with G protein-related genes during erythroid differentiation  

PubMed Central

Background The guanine nucleotide binding protein (G protein)-coupled receptors (GPCRs) regulate cell growth, proliferation and differentiation. G proteins are also implicated in erythroid differentiation, and some of them are expressed principally in hematopoietic cells. GPCRs-linked NO/cGMP and p38 MAPK signaling pathways already demonstrated potency for globin gene stimulation. By analyzing erythroid progenitors, derived from hematopoietic cells through in vitro ontogeny, our study intends to determine early markers and signaling pathways of globin gene regulation and their relation to GPCR expression. Results Human hematopoietic CD34+ progenitors are isolated from fetal liver (FL), cord blood (CB), adult bone marrow (BM), peripheral blood (PB) and G-CSF stimulated mobilized PB (mPB), and then differentiated in vitro into erythroid progenitors. We find that growth capacity is most abundant in FL- and CB-derived erythroid cells. The erythroid progenitor cells are sorted as 100% CD71+, but we did not find statistical significance in the variations of CD34, CD36 and GlyA antigens and that confirms similarity in maturation of studied ontogenic periods. During ontogeny, beta-globin gene expression reaches maximum levels in cells of adult blood origin (176 fmol/?g), while gamma-globin gene expression is consistently up-regulated in CB-derived cells (60 fmol/?g). During gamma-globin induction by hydroxycarbamide, we identify stimulated GPCRs (PTGDR, PTGER1) and GPCRs-coupled genes known to be activated via the cAMP/PKA (ADIPOQ), MAPK pathway (JUN) and NO/cGMP (PRPF18) signaling pathways. During ontogeny, GPR45 and ARRDC1 genes have the most prominent expression in FL-derived erythroid progenitor cells, GNL3 and GRP65 genes in CB-derived cells (high gamma-globin gene expression), GPR110 and GNG10 in BM-derived cells, GPR89C and GPR172A in PB-derived cells, and GPR44 and GNAQ genes in mPB-derived cells (high beta-globin gene expression). Conclusions These results demonstrate the concomitant activity of GPCR-coupled genes and related signaling pathways during erythropoietic stimulation of globin genes. In accordance with previous reports, the stimulation of GPCRs supports the postulated connection between cAMP/PKA and NO/cGMP pathways in activation of ?-globin expression, via JUN and p38 MAPK signaling.

2013-01-01

338

Elucidation of the functions of genes central to diterpene metabolism in tobacco trichomes using posttranscriptional gene silencing  

Microsoft Academic Search

The functions of two key, trichome-expressed genes were assessed using different posttranscriptional gene silencing strategies (PTGS). Efficient RNA interference (RNAi) revealed the function of a cembratriene-ol (CBT-ol) cyclase gene responsible for conversion of geranylgeranyl pyrophosphate to CBT-ols, and verified the function of a P450 gene responsible for conversion of CBT-ols to CBT-diols. CBT-diols are abundant diterpenes that comprise about 60%

Erming Wang; George J. Wagner

2003-01-01

339

Endosymbiont gene functions impaired and rescued by polymerase infidelity at poly(A) tracts  

PubMed Central

Among host-dependent bacteria that have evolved by extreme reductive genome evolution, long-term bacterial endosymbionts of insects have the smallest (160–790 kb) and most A + T-rich (>70%) bacterial genomes known to date. These genomes are riddled with poly(A) tracts, and 5–50% of genes contain tracts of 10 As or more. Here, we demonstrate transcriptional slippage at poly(A) tracts within genes of Buchnera aphidicola associated with aphids and Blochmannia pennsylvanicus associated with ants. Several tracts contain single frameshift deletions; these apparent pseudogenes showed patterns of constraint consistent with purifying selection on the encoded proteins. Transcriptional slippage yielded a heterogeneous population of transcripts with variable numbers of As in the tract. Across several frameshifted genes, including B. aphidicola cell wall biosynthesis genes and a B. pennsylvanicus histidine biosynthesis gene, 12–50% of transcripts contained corrected reading frames that could potentially yield full-length proteins. In situ immunostaining confirmed the production of the cell wall biosynthetic enzyme UDP-N-acetylmuramyl pentapeptide synthase encoded by the frameshifted murF gene. Simulation studies indicated an overrepresentation of poly(A) tracts in endosymbiont genomes relative to other A + T-rich bacterial genomes. Polymerase infidelity at poly(A) tracts rescues the functionality of genes with frameshift mutations and, conversely, reduces the efficiency of expression for in-frame genes carrying poly(A) regions. These features of homopolymeric tracts could be exploited to manipulate gene expression in small synthetic genomes.

Tamas, Ivica; Wernegreen, Jennifer J.; Nystedt, Bjorn; Kauppinen, Seth N.; Darby, Alistair C.; Gomez-Valero, Laura; Lundin, Daniel; Poole, Anthony M.; Andersson, Siv G. E.

2008-01-01

340

An autoregulated dual-function antitat gene for human immunodeficiency virus type 1 gene therapy.  

PubMed Central

One approach to gene therapy for AIDS is to block the replication of human immunodeficiency virus type 1 (HIV-1) by inhibiting that tat gene, whose product activates the expression of all HIV-1 genes. To accomplish this, we constructed an antitat gene expressing an RNA with dual (polymeric TAR and antisense-tat) function in an attempt to both sequester Tat protein and block its translation from mRNA. A minigene consisting of the antitat gene driven by the HIV-1 long terminal repeat was inserted into a double-copy retrovirus vector, such that antitat expression would be upregulated only in HIV-1-infected cells. After transduction of a T-lymphocytic cell line (Molt-3) the antitat gene inhibited HIV-1 replication. This inhibition was inversely correlated with the virus infections dose. Virus replication was also inhibited for 5 months in two different T-cell lines after they had been infected at a high multiplicity of infection, suggesting that the antitat gene may be effective over long periods. Importantly, antitat blocked the replication and the cytopathic effect of HIV-1 in human peripheral blood mononuclear cells and led to as much as 4,000-fold inhibition of the replication of an HIV-1 field isolate as well as HIV-1 prototypes maintained in culture. These results suggest that antitat gene therapy has potential use for blocking HIV-1 replication in infected individuals.

Lisziewicz, J; Sun, D; Trapnell, B; Thomson, M; Chang, H K; Ensoli, B; Peng, B

1995-01-01

341

Transglutaminase regulates immune-related genes in shrimp.  

PubMed

Transglutaminase (TGase) is known to be involved in blood coagulation, a conserved defence mechanism among invertebrates. Gene silencing of TGase was previously shown to render shrimp susceptible to both bacterial and viral infections suggesting that TGase is an essential component of the shrimp immune system. Here, we examine the effects of the absence of TGase on the transcriptomic profile of kuruma shrimp by microarray analysis, focussing on genes that are involved in shrimp immunity. Total RNAs from shrimp haemocytes injected with dsRNA specific for TGase and control samples were isolated at 3 and 7 days p.i. and analyzed by microarray. Results revealed that TGase silencing affects the expression of genes in shrimp and caused significant down-regulation of the expressions of crustin and lysozyme. Furthermore, TGase-depleted samples were found to have lower haemocyte counts and higher total bacterial counts in their haemolymph. These results suggest that TGase is an important component of the shrimp immune response and is involved in the regulation of some immune-related genes particularly antimicrobial peptides. PMID:22306779

Fagutao, Fernand F; Maningas, Mary Beth B; Kondo, Hidehiro; Aoki, Takashi; Hirono, Ikuo

2012-01-24

342

Relating protein adduction to gene expression changes: a systems approach  

PubMed Central

Modification of proteins by reactive electrophiles such as the 4-hydroxy-2-nonenal (HNE) plays a critical role in oxidant-associated human diseases. However, little is known about protein adduction and the mechanism by which protein damage elicits adaptive effects and toxicity. We developed a systems approach for relating protein adduction to gene expression changes through the integration of protein adduction, gene expression, protein-DNA interaction, and protein-protein interaction data. Using a random walk strategy, we expanded a list of responsive transcription factors inferred from gene expression studies to upstream signaling networks, which in turn allowed overlaying protein adduction data on the network for the prediction of stress sensors and their associated regulatory mechanisms. We demonstrated the general applicability of transcription factor-based signaling network inference using 103 known pathways. Applying our workflow on gene expression and protein adduction data from HNE-treatment not only rediscovered known mechanisms of electrophile stress but also generated novel hypotheses regarding protein damage sensors. Although developed for analyzing protein adduction data, the framework can be easily adapted for phosphoproteomics and other types of protein modification data.

Zhang, Bing; Shi, Zhiao; Duncan, Dexter T; Prodduturi, Naresh; Marnett, Lawrence J; Liebler, Daniel C

2013-01-01

343

MiR-210 disturbs mitotic progression through regulating a group of mitosis-related genes  

PubMed Central

MiR-210 is up-regulated in multiple cancer types but its function is disputable and further investigation is necessary. Using a bioinformatics approach, we identified the putative target genes of miR-210 in hypoxia-induced CNE cells from genome-wide scale. Two functional gene groups related to cell cycle and RNA processing were recognized as the major targets of miR-210. Here, we investigated the molecular mechanism and biological consequence of miR-210 in cell cycle regulation, particularly mitosis. Hypoxia-induced up-regulation of miR-210 was highly correlated with the down-regulation of a group of mitosis-related genes, including Plk1, Cdc25B, Cyclin F, Bub1B and Fam83D. MiR-210 suppressed the expression of these genes by directly targeting their 3?-UTRs. Over-expression of exogenous miR-210 disturbed mitotic progression and caused aberrant mitosis. Furthermore, miR-210 mimic with pharmacological doses reduced tumor formation in a mouse metastatic tumor model. Taken together, these results implicate that miR-210 disturbs mitosis through targeting multi-genes involved in mitotic progression, which may contribute to its inhibitory role on tumor formation.

He, Jie; Wu, Jiangbin; Xu, Naihan; Xie, Weidong; Li, Mengnan; Li, Jianna; Jiang, Yuyang; Yang, Burton B.; Zhang, Yaou

2013-01-01

344

An essential gene of Saccharomyces cerevisiae coding for an actin-related protein.  

PubMed Central

Actin filaments provide the internal scaffold of eukaryotic cells; they are involved in maintenance of cell shape, cytokinesis, organelle movement, and cell motility. The major component of these filaments, actin, is one of the most well-conserved eukaryotic proteins. Recently genes more distantly related to the conventional actins were cloned from several organisms. In the budding yeast, Saccharomyces cerevisiae, one conventional actin gene, ACT1 (coding for the filament actin), and a so-called actin-like gene, ACT2 (of unknown function), have so far been identified. We report here the discovery of a third member of the actin gene family from this organism, which we named ACT3. The latter gene is essential for viability and codes for a putative polypeptide, Act3, of 489 amino acids (M(r) = 54,831). The deduced amino acid sequence of Act3 is less related to conventional actins than is the deduced amino acid sequence of Act2, mainly because of three unique hydrophilic [corrected] segments. These segments are found inserted into a part of the sequence corresponding to a surface loop of the known three-dimensional structure of the actin molecule. According to sequence comparison, the basal core structure of conventional actin may well be conserved in Act3. Our findings demonstrate that, unexpectedly, there exist three members of the diverse actin protein family in budding yeast that obviously provide different essential functions for survival. Images

Harata, M; Karwan, A; Wintersberger, U

1994-01-01

345

Baculoviruses deficient in ie1 gene function abrogate viral gene expression in transduced mammalian cells  

SciTech Connect

One of the newest niches for baculoviruses-based technologies is their use as vectors for mammalian cell transduction and gene therapy applications. However, an outstanding safety issue related to such use is the residual expression of viral genes in infected mammalian cells. Here we show that infectious baculoviruses lacking the major transcriptional regulator, IE1, can be produced in insect host cells stably transformed with IE1 expression constructs lacking targets of homologous recombination that could promote the generation of wt-like revertants. Such ie1-deficient baculoviruses are unable to direct viral gene transcription to any appreciable degree and do not replicate in normal insect host cells. Most importantly, the residual viral gene expression, which occurs in mammalian cells infected with wt baculoviruses is reduced 10 to 100 fold in cells infected with ie1-deficient baculoviruses. Thus, ie1-deficient baculoviruses offer enhanced safety features to baculovirus-based vector systems destined for use in gene therapy applications.

Efrose, Rodica; Swevers, Luc; Iatrou, Kostas, E-mail: iatrou@bio.demokritos.g

2010-10-25

346

Modulation of adipogenesis-related gene expression by estrogen-related receptor ? during adipocytic differentiation  

Microsoft Academic Search

Estrogen-related receptor ? (ERR?) is an orphan nuclear receptor that regulates cellular energy metabolism by modulating gene expression involved in oxidative metabolism and mitochondrial biogenesis in brown adipose tissue and heart. However, the physiological role of ERR? in adipogenesis and the development of white adipose tissue has not been well studied. Here we show that ERR? was up-regulated in murine

Mayumi Kubo; Nobuhiro Ijichi; Kazuhiro Ikeda; Kuniko Horie-Inoue; Satoru Takeda; Satoshi Inoue

2009-01-01

347

Estrogen-related receptor ? modulates the expression of adipogenesis-related genes during adipocyte differentiation  

Microsoft Academic Search

Estrogen-related receptor ? (ERR?) is an orphan nuclear receptor that regulates cellular energy metabolism by modulating gene expression involved in fatty acid oxidation and mitochondrial biogenesis in brown adipose tissue. However, the physiological role of ERR? in adipogenesis and white adipose tissue development has not been well studied. Here, we show that ERR? and ERR?-related transcriptional coactivators, peroxisome proliferator-activated receptor

Nobuhiro Ijichi; Kazuhiro Ikeda; Kuniko Horie-Inoue; Ken Yagi; Yasushi Okazaki; Satoshi. Inoue

2007-01-01

348

Functional analysis of the two Brassica AP3 genes involved in apetalous and stamen carpelloid phenotypes.  

PubMed

The Arabidopsis homeotic genes APETALA3 (AP3) and PISTILLATA (PI) are B genes which encode MADS-box transcription factors and specify petal and stamen identities. In the current study, the stamen carpelloid (SC) mutants, HGMS and AMS, of B. rapa and B. napus were investigated and two types of AP3 genes, B.AP3.a and B.AP3.b, were functional characterized. B.AP3.a and B.AP3.b share high similarity in amino acid sequences except for 8 residues difference located at the C-terminus. Loss of this 8 residues in B.AP3.b led to the change of PI-derived motifs. Meanwhile, B.AP3.a specified petal and stamen development, whereas B.AP3.b only specified stamen development. In B. rapa, the mutations of both genes generated the SC mutant HGMS. In B. napus that contained two B.AP3.a and two B.AP3.b, loss of the two B.AP3.a functions was the key reason for the apetalous mutation, however, the loss-of-function in all four AP3 was related to the SC mutant AMS. We inferred that the 8 residues or the PI-derived motif in AP3 gene probably relates to petal formation. PMID:21738595

Zhang, Yanfeng; Wang, Xuefang; Zhang, Wenxue; Yu, Fei; Tian, Jianhua; Li, Dianrong; Guo, Aiguang

2011-06-30

349

Functional conservation of the promoter regions of vertebrate tyrosinase genes.  

PubMed

Tyrosinase is the key enzyme for synthesizing melanin pigments, which primarily determine mammalian skin coloration. Considering the important roles of pigments in the evolution and the adaptation of vertebrates, phylogenetic changes in the coding and flanking regulatory sequences of the tyrosinase gene are particularly intriguing. We have now cloned cDNA encoding tyrosinase from Japanese quail and snapping turtle. These nonmammalian cDNA are highly homologous to those of the mouse and human tyrosinases, whereas the 5' flanking sequences are far less conserved except for a few short sequence motifs. Nevertheless, we demonstrate that the 5' flanking sequences from the quail or turtle tyrosinase genes are capable of directing the expression of a fused mouse tyrosinase cDNA when introduced into cultured mouse albino melanocytes. This experimental method, which reveals the functional conservation of regulatory sequences in one cell type (the melanocyte), may be utilized to evaluate phylogenetic differences in mechanisms controlling specific gene expression in many other types of cells. We also provide evidence that the 5' flanking sequences from these nonmammalian genes are functional in vivo by producing transgenic mice. Phylogenetic changes of vertebrate tyrosinase promoters and the possible involvement of conserved sequence motifs in melanocyte-specific expression of tyrosinase are discussed. PMID:11764277

Sato, S; Tanaka, M; Miura, H; Ikeo, K; Gojobori, T; Takeuchi, T; Yamamoto, H

2001-11-01

350

Vertebrate pigmentation: from underlying genes to adaptive function.  

PubMed

Animal coloration is a powerful model for studying the genetic mechanisms that determine phenotype. Genetic crosses of laboratory mice have provided extensive information about the patterns of inheritance and pleiotropic effects of loci involved in pigmentation. Recently, the study of pigmentation genes and their functions has extended into wild populations, providing additional evidence that pigment gene function is largely conserved across disparate vertebrate taxa and can influence adaptive coloration, often in predictable ways. These new and integrative studies, along with those using a genetic approach to understand color perception, raise some important questions. Most notably, how does selection shape both phenotypic and genetic variation, and how can we use this information to further understand the phenotypic diversity generated by evolutionary processes? PMID:20381892

Hubbard, Joanna K; Uy, J Albert C; Hauber, Mark E; Hoekstra, Hopi E; Safran, Rebecca J

2010-04-08

351

Leaf functional traits of Neotropical savanna trees in relation to ...  

Treesearch

International Institute of Tropical Forestry ... Title: Leaf functional traits of Neotropical savanna trees in relation to seasonal water deficit. ... Their short leafless period and the capacity to flush by the end of the dry season may also contribute to ...

352

Robust extraction of functional signals from gene set analysis using a generalized threshold free scoring function  

PubMed Central

Background A central task in contemporary biosciences is the identification of biological processes showing response in genome-wide differential gene expression experiments. Two types of analysis are common. Either, one generates an ordered list based on the differential expression values of the probed genes and examines the tail areas of the list for over-representation of various functional classes. Alternatively, one monitors the average differential expression level of genes belonging to a given functional class. So far these two types of method have not been combined. Results We introduce a scoring function, Gene Set Z-score (GSZ), for the analysis of functional class over-representation that combines two previous analysis methods. GSZ encompasses popular functions such as correlation, hypergeometric test, Max-Mean and Random Sets as limiting cases. GSZ is stable against changes in class size as well as across different positions of the analysed gene list in tests with randomized data. GSZ shows the best overall performance in a detailed comparison to popular functions using artificial data. Likewise, GSZ stands out in a cross-validation of methods using split real data. A comparison of empirical p-values further shows a strong difference in favour of GSZ, which clearly reports better p-values for top classes than the other methods. Furthermore, GSZ detects relevant biological themes that are missed by the other methods. These observations also hold when comparing GSZ with popular program packages. Conclusion GSZ and improved versions of earlier methods are a useful contribution to the analysis of differential gene expression. The methods and supplementary material are available from the website http://ekhidna.biocenter.helsinki.fi/users/petri/public/GSZ/GSZscore.html.

2009-01-01

353

Functional gene group analysis identifies synaptic gene groups as risk factor for schizophrenia  

PubMed Central

Schizophrenia is a highly heritable disorder with a polygenic pattern of inheritance and a population prevalence of ?1%. Previous studies have implicated synaptic dysfunction in schizophrenia. We tested the accumulated association of genetic variants in expert-curated synaptic gene groups with schizophrenia in 4673 cases and 4965 healthy controls, using functional gene group analysis. Identifying groups of genes with similar cellular function rather than genes in isolation may have clinical implications for finding additional drug targets. We found that a group of 1026 synaptic genes was significantly associated with the risk of schizophrenia (P=7.6 × 10?11) and more strongly associated than 100 randomly drawn, matched control groups of genetic variants (P<0.01). Subsequent analysis of synaptic subgroups suggested that the strongest association signals are derived from three synaptic gene groups: intracellular signal transduction (P=2.0 × 10?4), excitability (P=9.0 × 10?4) and cell adhesion and trans-synaptic signaling (P=2.4 × 10?3). These results are consistent with a role of synaptic dysfunction in schizophrenia and imply that impaired intracellular signal transduction in synapses, synaptic excitability and cell adhesion and trans-synaptic signaling play a role in the pathology of schizophrenia.

Lips, E S; Cornelisse, L N; Toonen, R F; Min, J L; Hultman, C M; Holmans, P A; O'Donovan, M C; Purcell, S M; Smit, A B; Verhage, M; Sullivan, P F; Visscher, P M; Posthuma, D

2012-01-01

354

Functional and evolutionary inference in gene networks: does topology matter?  

Microsoft Academic Search

The relationship between the topology of a biological network and its functional or evolutionary properties has attracted\\u000a much recent interest. It has been suggested that most, if not all, biological networks are ‘scale free.’ That is, their connections\\u000a follow power-law distributions, such that there are very few nodes with very many connections and vice versa. The number of\\u000a target genes

Mark L. Siegal; Daniel E. L. Promislow; Aviv Bergman

2007-01-01

355

Tandem Riboswitch Architectures Exhibit Complex Gene Control Functions  

Microsoft Academic Search

Riboswitches are structured RNAs typically located in the 5' untranslated regions of bacterial mRNAs that bind metabolites and control gene expression. Most riboswitches sense one metabolite and function as simple genetic switches. However, we found that the 5' region of the Bacillus clausii metE messenger RNA includes two riboswitches that respond to S-adenosylmethionine and coenzyme B12. This tandem arrangement yields

Narasimhan Sudarsan; Ming C. Hammond; Kirsten F. Block; Rüdiger Welz; Jeffrey E. Barrick; Adam Roth; Ronald R. Breaker

2006-01-01

356

Status of genes encoding the mitochondrial S1 ribosomal protein in closely-related legumes.  

PubMed

The rps1 gene, which encodes ribosomal protein S1 of the mitochondrial ribosome in flowering plants, is located in the mitochondrion of some but not all species, and this is assumed to reflect multiple gene transfers to the nucleus. We investigated its status in legumes and found that in alfalfa, sweet clover and fenugreek, the mitochondrial-located rps1 is a pseudogene, in contrast to intact, transcribed and edited rps1 genes in the mitochondria of rest harrow, pea, soybean and bean. Among these lineages, the genomic environment upstream of rps1 differs, and this contrasts with a stable downstream linkage with the first two exons of the trans-split nad5 gene. Consequently, the rps1 transcript profiles differ for each of these closely-related species, and typically do not include monocistronic rps1 or nad5 mRNAs. In alfalfa, sweet clover and fenugreek, the functional rps1 gene is located in the nucleus and it is still flanked by residual non-coding mitochondrial sequences. Notably, the upstream ones provide part of the 5' UTR as well as the 3' splice site of an intron preceding rps1. This exploitation of non-coding mitochondrial sequences in nuclear gene activation adds to a growing list of mechanisms by which successful transfer of mitochondrial genes is achieved. PMID:17961935

Hazle, Thomas; Bonen, Linda

2007-10-03

357

Deciphering causal and statistical relations of molecular aberrations and gene expressions in NCI-60 cell lines  

PubMed Central

Background Cancer cells harbor a large number of molecular alterations such as mutations, amplifications and deletions on DNA sequences and epigenetic changes on DNA methylations. These aberrations may dysregulate gene expressions, which in turn drive the malignancy of tumors. Deciphering the causal and statistical relations of molecular aberrations and gene expressions is critical for understanding the molecular mechanisms of clinical phenotypes. Results In this work, we proposed a computational method to reconstruct association modules containing driver aberrations, passenger mRNA or microRNA expressions, and putative regulators that mediate the effects from drivers to passengers. By applying the module-finding algorithm to the integrated datasets of NCI-60 cancer cell lines, we found that gene expressions were driven by diverse molecular aberrations including chromosomal segments' copy number variations, gene mutations and DNA methylations, microRNA expressions, and the expressions of transcription factors. In-silico validation indicated that passenger genes were enriched with the regulator binding motifs, functional categories or pathways where the drivers were involved, and co-citations with the driver/regulator genes. Moreover, 6 of 11 predicted MYB targets were down-regulated in an MYB-siRNA treated leukemia cell line. In addition, microRNA expressions were driven by distinct mechanisms from mRNA expressions. Conclusions The results provide rich mechanistic information regarding molecular aberrations and gene expressions in cancer genomes. This kind of integrative analysis will become an important tool for the diagnosis and treatment of cancer in the era of personalized medicine.

2011-01-01

358

Computer Use and the Relation between Age and Cognitive Functioning  

ERIC Educational Resources Information Center

|This article investigates whether computer use for leisure could mediate or moderate the relations between age and cognitive functioning. Findings supported smaller age differences in measures of cognitive functioning for people who reported spending more hours using a computer. Because of the cross-sectional design of the study, two alternative…

Soubelet, Andrea

2012-01-01

359

Functional relation between two symmetric second-rank tensors  

NASA Astrophysics Data System (ADS)

The functional relationship between two symmetric second-rank tensors is considered. A new interpretation of the components of the tensors as projections onto an orthogonal tensor basis is given. It is shown that the constitutive relations can be written in the form of six functions each of which depends on one variable.

Ostrosablin, N. I.

2007-09-01

360

Protective Roles of ?-Calcitonin and ?-Calcitonin Gene-Related Peptide in Spontaneous and Experimentally Induced Colitis  

Microsoft Academic Search

Calcitonin gene-related peptide (CGRP) is thought to be involved in the regulation of gastric and mesenteric blood flow, in\\u000a the control of gastric acid secretion and in the modulation of intestinal motility, yet the precise physiological roles of\\u000a CGRP remain to be elucidated. To further examine the role(s) of CGRP in gastrointestinal function, we examined mutant mice\\u000a lacking ?CGRP or

Brent J. Thompson; Mary K. Washington; Usha Kurre; Minati Singh; Elizabeth Y. Rula; Ronald B. Emeson

2008-01-01

361

Age-related changes in gene expression in tissues of the sea urchin Strongylocentrotus purpuratus.  

PubMed

The life history of sea urchins is fundamentally different from that of traditional models of aging and therefore they provide the opportunity to gain new insight into this complex process. Sea urchins grow indeterminately, reproduce throughout their life span and some species exhibit negligible senescence. Using a microarray and qRT-PCR, age-related changes in gene expression were examined in three tissues (muscle, esophagus and nerve) of the sea urchin species Strongylocentrotus purpuratus. The results indicate age-related changes in gene expression involving many key cellular functions such as the ubiquitin-proteasome pathway, DNA metabolism, signaling pathways and apoptosis. Although there are tissue-specific differences in the gene expression profiles, there are some characteristics that are shared between tissues providing insight into potential mechanisms that promote lack of senescence in these animals. As an example, there is an increase in expression of genes encoding components of the Notch signaling pathway with age in all three tissues and a decrease in expression of the Wnt1 gene in both muscle and nerve. The interplay between the Notch and Wnt pathways may be one mechanism that ensures continued regeneration of tissues with advancing age contributing to the general lack of age-related decline in these animals. PMID:22475988

Loram, Jeannette; Bodnar, Andrea

2012-03-28

362

Identification of mycorrhiza-regulated genes with arbuscule development-related expression profile.  

PubMed

Suppressive subtractive hybridisation was applied to the analysis of late stage arbuscular mycorrhizal development in pea. 96 cDNA clones were amplified and 81, which carried fragments more than 200 nt in size, were sequence analysed. Among 67 unique fragments, 10 showed no homology and 10 were similar to sequences with unknown function. RNA accumulation of the corresponding 67 genes was analysed by hybridisation of macro-arrays. The cDNAs used as probes were derived from roots of wild type and late mutant pea genotypes, inoculated or not with the AM fungus Glomus mosseae. After calibration, a more than 2.5-fold mycorrhiza-induced RNA accumulation was detected in two independent experiments in the wild type for 25 genes, 22 of which seemed to be induced specifically during late stage AM development. Differential expression for 7 genes was confirmed by RT-PCR using RNA from mycorrhiza and from controls of a different pea cultivar. In order to confirm arbuscule-related expression, the Medicago truncatula EST data base was screened for homologous sequences with putative mycorrhiza-related expression and among a number of sequences with significant similarities, a family of trypsin inhibitor genes could be identified. Mycorrhiza-induced RNA accumulation was verified for five members by real-time PCR and arbuscule-related activation of the promoter could be shown in transgenic roots for one of the genes, MtTi 1. PMID:15604700

Grunwald, Ulf; Nyamsuren, Oyunbileg; Tamasloukht, M'Barek; Lapopin, Laurence; Becker, Anke; Mann, Petra; Gianinazzi-Pearson, Vivienne; Krajinski, Franziska; Franken, Philipp

2004-07-01

363

Gene fusions and gene duplications: relevance to genomic annotation and functional analysis  

Microsoft Academic Search

BACKGROUND: Escherichia coli a model organism provides information for annotation of other genomes. Our analysis of its genome has shown that proteins encoded by fused genes need special attention. Such composite (multimodular) proteins consist of two or more components (modules) encoding distinct functions. Multimodular proteins have been found to complicate both annotation and generation of sequence similar groups. Previous work

Margrethe H Serres; Monica Riley

2005-01-01

364

A Bayesian Approach to Pathway Analysis by Integrating Gene-Gene Functional Directions and Microarray Data  

PubMed Central

Many statistical methods have been developed to screen for differentially expressed genes associated with specific phenotypes in the microarray data. However, it remains a major challenge to synthesize the observed expression patterns with abundant biological knowledge for more complete understanding of the biological functions among genes. Various methods including clustering analysis on genes, neural network, Bayesian network and pathway analysis have been developed toward this goal. In most of these procedures, the activation and inhibition relationships among genes have hardly been utilized in the modeling steps. We propose two novel Bayesian models to integrate the microarray data with the putative pathway structures obtained from the KEGG database and the directional gene–gene interactions in the medical literature. We define the symmetric Kullback–Leibler divergence of a pathway, and use it to identify the pathway(s) most supported by the microarray data. Monte Carlo Markov Chain sampling algorithm is given for posterior computation in the hierarchical model. The proposed method is shown to select the most supported pathway in an illustrative example. Finally, we apply the methodology to a real microarray data set to understand the gene expression profile of osteoblast lineage at defined stages of differentiation. We observe that our method correctly identifies the pathways that are reported to play essential roles in modulating bone mass.

Zhao, Yifang; Chen, Ming-Hui; Pei, Baikang; Rowe, David; Shin, Dong-Guk; Xie, Wangang; Yu, Fang; Kuo, Lynn

2012-01-01