These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

SOX9 Regulates Multiple Genes in Chondrocytes, Including Genes Encoding ECM Proteins, ECM Modification Enzymes, Receptors, and Transporters  

PubMed Central

The transcription factor SOX9 plays an essential role in determining the fate of several cell types and is a master factor in regulation of chondrocyte development. Our aim was to determine which genes in the genome of chondrocytes are either directly or indirectly controlled by SOX9. We used RNA-Seq to identify genes whose expression levels were affected by SOX9 and used SOX9 ChIP-Seq to identify those genes that harbor SOX9-interaction sites. For RNA-Seq, the RNA expression profile of primary Sox9flox/flox mouse chondrocytes infected with Ad-CMV-Cre was compared with that of the same cells infected with a control adenovirus. Analysis of RNA-Seq data indicated that, when the levels of Sox9 mRNA were decreased more than 8-fold by infection with Ad-CMV-Cre, 196 genes showed a decrease in expression of at least 4-fold. These included many cartilage extracellular matrix (ECM) genes and a number of genes for ECM modification enzymes (transferases), membrane receptors, transporters, and others. In ChIP-Seq, 75% of the SOX9-interaction sites had a canonical inverted repeat motif within 100 bp of the top of the peak. SOX9-interaction sites were found in 55% of the genes whose expression was decreased more than 8-fold in SOX9-depleted cells and in somewhat fewer of the genes whose expression was reduced more than 4-fold, suggesting that these are direct targets of SOX9. The combination of RNA-Seq and ChIP-Seq has provided a fuller understanding of the SOX9-controlled genetic program of chondrocytes. PMID:25229425

Oh, Chun-do; Lu, Yue; Liang, Shoudan; Mori-Akiyama, Yuko; Chen, Di; de Crombrugghe, Benoit; Yasuda, Hideyo

2014-01-01

2

The Medicago truncatula Lysine Motif-Receptor-Like Kinase Gene Family Includes NFP and New Nodule-Expressed Genes1[W  

PubMed Central

Rhizobial Nod factors are key symbiotic signals responsible for starting the nodulation process in host legume plants. Of the six Medicago truncatula genes controlling a Nod factor signaling pathway, Nod Factor Perception (NFP) was reported as a candidate Nod factor receptor gene. Here, we provide further evidence for this by showing that NFP is a lysine motif (LysM)-receptor-like kinase (RLK). NFP was shown both to be expressed in association with infection thread development and to be involved in the infection process. Consistent with deviations from conserved kinase domain sequences, NFP did not show autophosphorylation activity, suggesting that NFP needs to associate with an active kinase or has unusual functional characteristics different from classical kinases. Identification of nine new M. truncatula LysM-RLK genes revealed a larger family than in the nonlegumes Arabidopsis (Arabidopsis thaliana) or rice (Oryza sativa) of at least 17 members that can be divided into three subfamilies. Three LysM domains could be structurally predicted for all M. truncatula LysM-RLK proteins, whereas one subfamily, which includes NFP, was characterized by deviations from conserved kinase sequences. Most of the newly identified genes were found to be expressed in roots and nodules, suggesting this class of receptors may be more extensively involved in nodulation than was previously known. PMID:16844829

Arrighi, Jean-François; Barre, Annick; Ben Amor, Besma; Bersoult, Anne; Soriano, Lidia Campos; Mirabella, Rossana; de Carvalho-Niebel, Fernanda; Journet, Etienne-Pascal; Ghérardi, Michèle; Huguet, Thierry; Geurts, René; Dénarié, Jean; Rougé, Pierre; Gough, Clare

2006-01-01

3

Taste Receptor Genes  

PubMed Central

In the past several years, tremendous progress has been achieved with the discovery and characterization of vertebrate taste receptors from the T1R and T2R families, which are involved in recognition of bitter, sweet, and umami taste stimuli. Individual differences in taste, at least in some cases, can be attributed to allelic variants of the T1R and T2R genes. Progress with understanding how T1R and T2R receptors interact with taste stimuli and with identifying their patterns of expression in taste cells sheds light on coding of taste information by the nervous system. Candidate mechanisms for detection of salts, acids, fat, complex carbohydrates, and water have also been proposed, but further studies are needed to prove their identity. PMID:17444812

Bachmanov, Alexander A.; Beauchamp, Gary K.

2009-01-01

4

Melatonin receptor genes in vertebrates.  

PubMed

Melatonin receptors are members of the G protein-coupled receptor (GPCR) family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A) and MT2 (or Mel1b or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C), has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor. PMID:23712359

Li, Di Yan; Smith, David Glenn; Hardeland, Rüdiger; Yang, Ming Yao; Xu, Huai Liang; Zhang, Long; Yin, Hua Dong; Zhu, Qing

2013-01-01

5

Melatonin Receptor Genes in Vertebrates  

PubMed Central

Melatonin receptors are members of the G protein-coupled receptor (GPCR) family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A) and MT2 (or Mel1b or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C), has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor. PMID:23712359

Li, Di Yan; Smith, David Glenn; Hardeland, Rüdiger; Yang, Ming Yao; Xu, Huai Liang; Zhang, Long; Yin, Hua Dong; Zhu, Qing

2013-01-01

6

Original article Effect of including major gene  

E-print Network

was mostly efficient in the medium and long term when the gene was rare and recessive and in the medium term and to a limited risk of losing it by genetic drift for a rare recessive gene. major gene / QTL / selection / MonteOriginal article Effect of including major gene information in mass selection: a stochastic

Paris-Sud XI, Université de

7

Common Worldwide Variation Discovered in Human Taste Receptor Genes  

MedlinePLUS

... Taste Receptor Genes Common Worldwide Variation Discovered In Human Taste Receptor Genes Common Worldwide Variation Discovered In Human Taste Receptor Genes Background : Differences in our sense ...

8

Partial cloning and differential expression of ryanodine receptor\\/calcium-release channel genes in human tissues including the hippocampus and cerebellum  

Microsoft Academic Search

Cellular Ca2+ signalling is an important factor in the control of neuronal metabolism and electrical activity. Although the roles of Ca2+-release channels are well established for skeletal and cardiac muscle, less is known about their expression and roles in the central nervous system, especially in the human brain. We have isolated partial complementary DNAs derived from the human ryanodine receptor

C Martin; K. E Chapman; J. R Seckl; R. H Ashley

1998-01-01

9

Activation of Intracellular Metabotropic Glutamate Receptor 5 in Striatal Neurons Leads to Up-regulation of Genes Associated with Sustained Synaptic Transmission Including Arc/Arg3.1 Protein*  

PubMed Central

The G-protein coupled receptor, metabotropic glutamate receptor 5 (mGluR5), is expressed on both cell surface and intracellular membranes in striatal neurons. Using pharmacological tools to differentiate membrane responses, we previously demonstrated that cell surface mGluR5 triggers rapid, transient cytoplasmic Ca2+ rises, resulting in c-Jun N-terminal kinase, Ca2+/calmodulin-dependent protein kinase, and cyclic adenosine 3?,5?-monophosphate-responsive element-binding protein (CREB) phosphorylation, whereas stimulation of intracellular mGluR5 induces long, sustained Ca2+ responses leading to the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and Elk-1 (Jong, Y. J., Kumar, V., and O'Malley, K. L. (2009) J. Biol. Chem. 284, 35827–35838). Using pharmacological, genetic, and bioinformatics approaches, the current findings show that both receptor populations up-regulate many immediate early genes involved in growth and differentiation. Activation of intracellular mGluR5 also up-regulates genes involved in synaptic plasticity including activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mechanistically, intracellular mGluR5-mediated Arc induction is dependent upon extracellular and intracellular Ca2+ and ERK1/2 as well as calmodulin-dependent kinases as known chelators, inhibitors, and a dominant negative Ca2+/calmodulin-dependent protein kinase II construct block Arc increases. Moreover, intracellular mGluR5-induced Arc expression requires the serum response transcription factor (SRF) as wild type but not SRF-deficient neurons show this response. Finally, increased Arc levels due to high K+ depolarization is significantly reduced in response to a permeable but not an impermeable mGluR5 antagonist. Taken together, these data highlight the importance of intracellular mGluR5 in the cascade of events associated with sustained synaptic transmission. PMID:22179607

Kumar, Vikas; Fahey, Paul G.; Jong, Yuh-Jiin I.; Ramanan, Narendrakumar; O'Malley, Karen L.

2012-01-01

10

Gene expression pattern Embryonic expression of a P2X3 receptor encoding gene in zebrash  

E-print Network

Gene expression pattern Embryonic expression of a P2X3 receptor encoding gene in zebra®sh William H genes during early development. Here we describe the expression of a gene (p2x3) encoding a P2X3., 1998; Xiang et al., 1998) that include the nociceptive neurones of the trigem- inal and dorsal root

Burnstock, Geoffrey

11

Selective Pressures on Drosophila Chemosensory Receptor Genes  

Microsoft Academic Search

The evolution and patterns of selection of genes encoding 10 Drosophila odorant receptors (Or) and the sex pheromone receptor Gr68a were investigated by comparing orthologous sequences across five\\u000a to eight ecologically diverse species of Drosophila. Using maximum likelihood estimates of dN\\/dS ratios we show that all 11 genes sampled are under purifying selection, indicating\\u000a functional constraint. Four of these genes

Narelle E. Tunstall; Tamara Sirey; Richard D. Newcomb; Coral G. Warr

2007-01-01

12

Thyroid hormone receptor genes of neotenic amphibians.  

PubMed

Since thyroid hormones play a pivotal role in amphibian metamorphosis we used PCR to amplify DNA fragments corresponding to a portion of the ligand-binding domain of the thyroid hormone receptor (TR) genes in several neotenic amphibians: the obligatory neotenic members of the family Proteidea the mudpuppy Necturus maculosus and Proteus anguinus as well as two members of the facultative neotenic Ambystoma genus: the axolotl Ambystoma mexicanum and the tiger salamander Ambystoma tigrinum. In addition, we looked for TR genes in the genome of an apode Typhlonectes compressicaudus. TR genes were found in all these species including the obligatory neotenic ones. The PCR fragments obtained encompass both the C and E domains and correspond to alpha and beta genes. Their sequences appear to be normal, suggesting that there is no acceleration of evolutionary rates in the TR genes of neotenic amphibians. This result is not surprising for Ambystomatidae, which are known to respond to T3 (3,3',5-triiodothyronine) but is not in agreement with biochemical and biological data showing that Proteidea cannot respond to thyroid hormones. Interestingly, by RT-PCR analysis we observed a high expression levels of TRalpha in gills, intestine, and muscles of Necturus as well as in the liver of Ambystoma mexicanum, whereas TRbeta expression was only detected in Ambystoma mexicanum but not in Necturus. Such a differential expression pattern of TRalpha and TRbeta may explain the neoteny in Proteidea. The cloning of thyroid-hormone-receptor gene fragments from these species will allow the molecular study of their failure to undergo metamorphosis. PMID:9169551

Safi, R; Begue, A; Hänni, C; Stehelin, D; Tata, J R; Laudet, V

1997-06-01

13

Dopamine receptor genes: new tools for molecular psychiatry.  

PubMed Central

For over a decade it has been generally assumed that all the pharmacological and biochemical actions of dopamine within the central nervous system and periphery were mediated by two distinct dopamine receptors. These receptors, termed D1 and D2, were defined as those coupled to the stimulation or inhibition of adenylate cyclase, respectively, and by their selectivity and avidity for various drugs and compounds. The concept that two dopamine receptors were sufficient to account for all the effects mediated by dopamine was an oversimplification. Recent molecular biological studies have identified five distinct genes which encode at least eight functional dopamine receptors. The members of the expanded dopamine receptor family, however, can still be codifed by way of the original D1 and D2 receptor dichotomy. These include two genes encoding dopamine D1-like receptors (D1 [D1A]/D5 [D1B]) and three genes encoding D2-like receptors (D2/D3/D4). We review here our recent work on the cloning and characterization of some of the members of the dopamine receptor gene family (D1, D2, D4, D5), their relationship to neuropsychiatric disorders and their potential role in antipsychotic drug action. Images Fig. 1 PMID:1450188

Niznik, H B; Van Tol, H H

1992-01-01

14

Promoter architecture of mouse olfactory receptor genes  

PubMed Central

Odorous chemicals are detected by the mouse main olfactory epithelium (MOE) by about 1100 types of olfactory receptors (OR) expressed by olfactory sensory neurons (OSNs). Each mature OSN is thought to express only one allele of a single OR gene. Major impediments to understand the transcriptional control of OR gene expression are the lack of a proper characterization of OR transcription start sites (TSSs) and promoters, and of regulatory transcripts at OR loci. We have applied the nanoCAGE technology to profile the transcriptome and the active promoters in the MOE. nanoCAGE analysis revealed the map and architecture of promoters for 87.5% of the mouse OR genes, as well as the expression of many novel noncoding RNAs including antisense transcripts. We identified candidate transcription factors for OR gene expression and among them confirmed by chromatin immunoprecipitation the binding of TBP, EBF1 (OLF1), and MEF2A to OR promoters. Finally, we showed that a short genomic fragment flanking the major TSS of the OR gene Olfr160 (M72) can drive OSN-specific expression in transgenic mice. PMID:22194471

Plessy, Charles; Pascarella, Giovanni; Bertin, Nicolas; Akalin, Altuna; Carrieri, Claudia; Vassalli, Anne; Lazarevic, Dejan; Severin, Jessica; Vlachouli, Christina; Simone, Roberto; Faulkner, Geoffrey J.; Kawai, Jun; Daub, Carsten O.; Zucchelli, Silvia; Hayashizaki, Yoshihide; Mombaerts, Peter; Lenhard, Boris; Gustincich, Stefano; Carninci, Piero

2012-01-01

15

Expression of plasma membrane receptor genes during megakaryocyte development  

PubMed Central

Megakaryocyte (MK) development is critically informed by plasma membrane-localized receptors that integrate a multiplicity of environmental cues. Given that the current understanding about receptors and ligands involved in megakaryocytopoiesis is based on single targets, we performed a genome-wide search to identify a plasma membrane receptome for developing MKs. We identified 40 transmembrane receptor genes as being upregulated during MK development. Seven of the 40 receptor-associated genes were selected to validate the dataset. These genes included: interleukin-9 receptor (IL9R), transforming growth factor, ? receptor II (TGFBR2), interleukin-4 receptor (IL4R), colony stimulating factor-2 receptor-beta (CSFR2B), adiponectin receptor (ADIPOR2), thrombin receptor (F2R), and interleukin-21 receptor (IL21R). RNA and protein analyses confirmed their expression in primary human MKs. Matched ligands to IL9R, TGFBR2, IL4R, CSFR2B, and ADIPOR2 affected megakaryocytopoiesis. IL9 was unique in its ability to increase the number of MKs formed. In contrast, MK colony formation was inhibited by adiponectin, TGF-?, IL4, and GM-CSF. The thrombin-F2R axis affected platelet function, but not MK development, while IL21 had no apparent detectable effects. ADP-induced platelet aggregation was suppressed by IL9, TGF-?, IL4, and adiponectin. Overall, six of seven of the plasma membrane receptors were confirmed to have functional roles in MK and platelet biology. Also, results show for the first time that adiponectin plays a regulatory role in MK development. Together these data support a strong likelihood that the 40 transmembrane genes identified as being upregulated during MK development will be an important resource to the research community for deciphering the complex repertoire of environmental cues regulating megakaryocytopoiesis and/or platelet function. PMID:23321270

Sun, Sijie; Wang, Wenjing; Latchman, Yvette; Gao, Dayong; Aronow, Bruce

2013-01-01

16

Childhood Atopic Asthma: Positive Association with a Polymorphism of IL4 Receptor ? Gene but Not with That of IL4 Promoter or Fc ε Receptor I ? Gene  

Microsoft Academic Search

We examined the relative contributions of three representative candidate genes for atopy (Fc ε receptor I ?, IL-4, and IL-4 receptor ?) to the development of atopic asthma. Four polymorphisms of the three candidate genes including Ile50Val and Gln551Arg of IL-4 receptor ?, -590C\\/T of IL-4 promoter and Glu237Gly of Fc ε receptor I ? were studied in 100 patients

Akira Takabayashi; Kenji Ihara; Yuka Sasaki; Yuzo Suzuki; Sankei Nishima; Kenji Izuhara; Naotaka Hamasaki; Toshiro Hara

2000-01-01

17

Virus-Induced Transcriptional Changes in the Brain Include the Differential Expression of Genes Associated with Interferon, Apoptosis, Interleukin 17 Receptor A, and Glutamate Signaling as Well as Flavivirus-Specific Upregulation of tRNA Synthetases  

PubMed Central

ABSTRACT Flaviviruses, particularly Japanese encephalitis virus (JEV) and West Nile virus (WNV), are important causes of virus-induced central nervous system (CNS) disease in humans. We used microarray analysis to identify cellular genes that are differentially regulated following infection of the brain with JEV (P3) or WNV (New York 99). Gene expression data for these flaviviruses were compared to those obtained following infection of the brain with reovirus (type 3 Dearing), an unrelated neurotropic virus. We found that a large number of genes were up-regulated by all three viruses (using the criteria of a change of >2-fold and a P value of <0.001), including genes associated with interferon signaling, the immune system, inflammation, and cell death/survival signaling. In addition, genes associated with glutamate signaling were down-regulated in infections with all three viruses (criteria, a >2-fold change and a P value of <0.001). These genes may serve as broad-spectrum therapeutic targets for virus-induced CNS disease. A distinct set of genes were up-regulated following flavivirus infection but not following infection with reovirus. These genes were associated with tRNA charging and may serve as therapeutic targets for flavivirus-induced CNS disease. PMID:24618253

Clarke, Penny; Leser, J. Smith; Bowen, Richard A.; Tyler, Kenneth L.

2014-01-01

18

Chromosome 11: gene for dopamine receptors, Matt RidleySite: DNA Interactive (www.dnai.org)  

NSDL National Science Digital Library

Interviewee: Matt Ridley DNAi Location:Genome>tour>genome spots>Dopamine receptor Location: chromosome 11 gene name: D4DR (dopamine receptor) This gene on chromosome 11 appears to influence personality. The protein produced from this gene is a receptor for the neurotransmitter dopamine. Dopamine pathways control many aspects of the brain, including blood flow. If this gene contains many repeated sequences the person is less responsive to dopamine and more likely to seek external "thrills" in their lives.

2008-10-06

19

Identification of an Orphan Receptor Gene as a Type 1 Calcitonin Gene-Related Peptide Receptor  

Microsoft Academic Search

Calcitonin gene-related peptide (CGRP) is a 37 residue neuropeptide that is distantly related to adrenomedullin, We have recently reported the cloning and expression of an adrenomedullin receptor which is ? 30% homologous to the canine orphan receptor RDC-1. Therefore we tested the hypothesis that RDC-1 was a CGRP receptor. The RDC-1 gene was expressed in COS-7 cells and showed a

S. Kapas; A. J. L. Clark

1995-01-01

20

Pharmacogenetics of the ?2-Adrenergic Receptor Gene  

PubMed Central

Asthma is a complex genetic disease with multiple genetic and environmental determinants contributing to the observed variability in response to common anti-asthma therapies. Asthma pharmacogenetic research has focused on multiple candidate genes including the ?2-adrenergic receptor gene (ADR?2) and its effect on individual responses to beta agonist therapy. At present, knowledge about the effects of ADR?2 variation on therapeutic responses is evolving and should not alter current Asthma Guideline approaches consisting of the use of short acting beta agonists for as-needed symptom based therapy and the use of a regular long-acting beta agonist in combination with inhaled corticosteroid therapy for optimal control of asthma symptoms in those asthmatics who are not controlled on inhaled corticosteroid alone. This approach is based upon studies showing a consistent pharmacogenetic response to regular use of short acting beta agonists (SABA) and less consistent findings in studies evaluating long acting beta agonist (LABA). While emerging pharmacogenetic studies are provocative and should lead to functional approaches, conflicting data with responses to LABA therapy may be caused by factors that include small sample sizes of study populations and differences in experimental design that may limit the conclusions that may be drawn from these clinical trials at the present time. PMID:17996583

Ortega, Victor E.; Hawkins, Gregory A.; Peters, Stephen P.; Bleecker, Eugene R.

2009-01-01

21

PPAR ? agonist GW0742 interacts weakly with multiple nuclear receptors including the vitamin D receptor  

PubMed Central

A high throughput screening campaign was conducted to identify small molecules with the ability to inhibit the interaction between the vitamin D receptor (VDR) and steroid receptor coactivator 2. These inhibitors represent novel molecular probes to modulate gene regulation mediated by VDR. The peroxisome proliferator-activated receptor ? (PPAR?) agonist GW0742 was among the identified VDR-coactivator inhibitors and has been characterized herein as a pan nuclear receptor antagonist at concentrations higher than 12.1 µM. The highest antagonist activity for GW0742 was found for VDR and the androgen receptor (AR). Surprisingly, GW0742 behaved as PPAR agonist/antagonist activating transcription at lower concentration and inhibiting this effect at higher concentrations. A unique spectroscopic property of GW0742 was identified as well. In the presence of rhodamine-derived molecules, GW0742+ increased fluorescence intensity and fluorescence polarization at an excitation wavelength of 595 nm and emission wavelength of 615 nm in a dose dependent manner. The GW0742-inhibited NR-coactivator binding resulted in a reduced expression of five different NR target genes in LNCaP cells in the presence of agonist. Especially VDR target genes CYP24A1, IGFBP-3 and TRPV6 were negatively regulated by GW0742. GW0742 is the first VDR ligand inhibitor lacking the secosteroid structure of VDR ligand antagonists. Nevertheless, the VDR-meditated downstream process of cell differentiation was antagonized by GW0742 in HL-60 cells that were pretreated with the endogenous VDR agonist 1,25-dihydroxyvitamin D3. PMID:23713684

Nandhikonda, Premchendar; Yasgar, Adam; Baranowski, Athena M.; Sidhu, Preetpal S.; McCallum, Megan M.; Pawlak, Alan J.; Teske, Kelly; Feleke, Belaynesh; Yuan, Nina Y.; Kevin, Chinedum; Bikle, Daniel D.; Ayers, Steven D.; Webb, Paul; Rai, Ganesha; Simeonov, Anton; Jadhav, Ajit; Maloney, David; Arnold, Leggy A.

2013-01-01

22

Epigenetic regulation of antigen receptor gene rearrangement  

PubMed Central

Summary Recent studies of the regulation of antigen receptor rearrangement have revealed several completely new levels of control. Not only do antigen receptor loci undergo changes in histone modifications as they become accessible for recombination, but the number of different histone modifications and the variation at different parts of each receptor locus reveal great complexity. RAG2 is now known to bind to one of these histone modifications, H3K4me3, and this targets the initial RAG binding events to the J genes. The large megabase receptor loci undergo 3-D changes in their structure during rearrangement, and receptor loci move throughout the nucleus, transiently binding to heterochromatin, and transiently pairing with each other. RAG-mediated DNA breaks promote some of these movements, and also result in widespread changes in the transcriptional profile promoting differentiation. PMID:21216580

Feeney, Ann J.

2011-01-01

23

Candidate gene analysis of thyroid hormone receptors in metamorphosing  

E-print Network

Candidate gene analysis of thyroid hormone receptors in metamorphosing vs. nonmetamorphosing experimental approaches to test the hypothesis that thyroid hormone receptor (TR) variation is associated: Ambystoma, metamorphic failure, metamorphosis, thyroid hormone, thyroid hormone receptor. Introduction Post

Grether, Gregory

24

The Androgen Receptor Gene Mutations Database  

Microsoft Academic Search

The current version of the androgen receptor (AR) gene mutations database is described. The total number of reported mutations has risen from 272 to 309 in the past year. We have expanded the database: (i) by giving each entry an accession number; (ii) by adding information on the length of polymorphic polyglutamine (polyGln) and polyglycine (polyGly) tracts in exon 1;

Bruce Gottlieb; Heikki Lehväslaiho; Lenore K. Beitel; Rose Lumbroso; Leonard Pinsky; Mark Trifiro

1998-01-01

25

The cyclic-AMP receptor protein (CRP) regulon in Aggregatibacter actinomycetemcomitans includes leukotoxin  

PubMed Central

The cyclic-AMP receptor protein (CRP) acts as a global regulatory protein among bacteria. Here, the CRP regulon has been defined in Aggregatibacter actinomycetemcomitans using microarray analysis of A. actinomycetemcomitans strain JP2 wild type cells compared to an isogenic crp deletion mutant. Genes whose expression levels changed at least 2-fold with p ? 0.05 were considered significant. Of the 300 genes identified as being CRP-regulated, 139 were CRP-activated, including leukotoxin, with the remaining being CRP-repressed. The 300 genes represent 14.2% of ORFs probed which is significantly higher than what has been reported for CRP regulons in other bacteria. If the CRP-regulated genes are put into 17 functional classes, all 17 categories had at least 1 CRP-regulated gene. Several functional categories, mainly transport and binding proteins and energy metabolism proteins, were disproportionately represented in the CRP-regulated subset of genes relative to their overall representation in the genome. This is similar to the patterns seen in other bacteria. Finally, quantitative RT-PCR was used to show that the leukotoxin RNA levels were repressed 16-fold in the CRP mutant indicating that CRP activates leukotoxin transcription. However, this regulation appears to be acting through another regulatory protein since the leukotoxin promoter, unlike ~129 other promoters of CRP-regulated genes, does not have a match to the consensus CRP binding site. Several candidate genes for this intermediary transcription factor have been identified in the CRP-regulon. PMID:21575705

Feuerbacher, Leigh A.; Burgum, Alex; Kolodrubetz, David

2011-01-01

26

Extrasynaptic NMDA Receptors Reshape Gene Ranks  

NSDL National Science Digital Library

The N-methyl-D-aspartate (NMDA) subtype of glutamate receptors (NMDAR) plays a key role in the control of neuronal plasticity and cell survival by modifying the activity of different signaling pathways and numerous genes. However, it remains unclear how the activation of this one class of glutamate receptors can lead to different functional consequences, such as enhancement of neuronal survival or induction of neuronal death. Recent work further refines the hypothesis that synaptic and extrasynaptic NMDARs have distinct roles in neuronal survival and death by showing that these two subpopulations of NMDARs differentially modify whole-genome activity.

Igor Medina (INSERM; Mediterranean Institute of Neurobiology (INMED) REV)

2007-05-15

27

Includes pre-computed gene families, multiple sequence  

E-print Network

genomes from flowering plants, (club-)mosses and several green algae · All data can be downloaded PLAZA release 2.5 · Includes >900,000 genes from 25 plants covering 13 dicots, 5 monocots, 2 (club-)mosses

Gent, Universiteit

28

Includes pre-computed gene families, multiple sequence alignments &  

E-print Network

23 plants covering 11 dicots, 5 monocots, 2 (club-)mosses and 5 algae · Advanced panel of (inter to perform analyses on their genes · Includes published genomes from flowering plants, mosses and several

Gent, Universiteit

29

Social regulation of cortisol receptor gene expression.  

PubMed

In many social species, individuals influence the reproductive capacity of conspecifics. In a well-studied African cichlid fish species, Astatotilapia burtoni, males are either dominant (D) and reproductively competent or non-dominant (ND) and reproductively suppressed as evidenced by reduced gonadotropin releasing hormone (GnRH1) release, regressed gonads, lower levels of androgens and elevated levels of cortisol. Here, we asked whether androgen and cortisol levels might regulate this reproductive suppression. Astatotilapia burtoni has four glucocorticoid receptors (GR1a, GR1b, GR2 and MR), encoded by three genes, and two androgen receptors (AR? and AR?), encoded by two genes. We previously showed that AR? and AR? are expressed in GnRH1 neurons in the preoptic area (POA), which regulates reproduction, and that the mRNA levels of these receptors are regulated by social status. Here, we show that GR1, GR2 and MR mRNAs are also expressed in GnRH1 neurons in the POA, revealing potential mechanisms for both androgens and cortisol to influence reproductive capacity. We measured AR, MR and GR mRNA expression levels in a microdissected region of the POA containing GnRH1 neurons, comparing D and ND males. Using quantitative PCR (qPCR), we found D males had higher mRNA levels of AR?, MR, total GR1a and GR2 in the POA compared with ND males. In contrast, ND males had significantly higher levels of GR1b mRNA, a receptor subtype with a reduced transcriptional response to cortisol. Through this novel regulation of receptor type, neurons in the POA of an ND male will be less affected by the higher levels of cortisol typical of low status, suggesting GR receptor type change as a potential adaptive mechanism to mediate high cortisol levels during social suppression. PMID:25013108

Korzan, Wayne J; Grone, Brian P; Fernald, Russell D

2014-09-15

30

Thyroid Hormone Receptor Genes of Neotenic Amphibians  

Microsoft Academic Search

.   Since thyroid hormones play a pivotal role in amphibian metamorphosis we used PCR to amplify DNA fragments corresponding\\u000a to a portion of the ligand-binding domain of the thyroid hormone receptor (TR) genes in several neotenic amphibians: the obligatory\\u000a neotenic members of the family Proteidea the mudpuppy Necturus maculosus and Proteus anguinus as well as two members of the facultative

Rachid Safi; Agnès Begue; Catherine Hänni; Dominique Stehelin; Jamshed R. Tata; Vincent Laudet

1997-01-01

31

Glucocorticoid Receptor-Dependent Gene Regulatory Networks  

PubMed Central

While the molecular mechanisms of glucocorticoid regulation of transcription have been studied in detail, the global networks regulated by the glucocorticoid receptor (GR) remain unknown. To address this question, we performed an orthogonal analysis to identify direct targets of the GR. First, we analyzed the expression profile of mouse livers in the presence or absence of exogenous glucocorticoid, resulting in over 1,300 differentially expressed genes. We then executed genome-wide location analysis on chromatin from the same livers, identifying more than 300 promoters that are bound by the GR. Intersecting the two lists yielded 53 genes whose expression is functionally dependent upon the ligand-bound GR. Further network and sequence analysis of the functional targets enabled us to suggest interactions between the GR and other transcription factors at specific target genes. Together, our results further our understanding of the GR and its targets, and provide the basis for more targeted glucocorticoid therapies. PMID:16110340

Phuc Le, Phillip; Friedman, Joshua R; Schug, Jonathan; Brestelli, John E; Parker, J. Brandon; Bochkis, Irina M; Kaestner, Klaus H

2005-01-01

32

The S15 Self-Incompatibility Haplotype in Brassica oleracea Includes Three S Gene Family Members Expressed in Stigmas  

Microsoft Academic Search

Self-incompatibility in Brassica is controlled by a single, highly polymorphic locus that extends over several hundred ki- lobases and includes several expressed genes. Two stigma proteins, the S locus receptor kinase (SRK) and the S locus glycoprotein (SLG), are encoded by genes located at the S locus and are thought to be involved in the recognition of self-pollen by the

Didier Cabrillac; Valérie Delorme; Jerome Garin; Véronique Ruffio-Châble; Jean-Loïc Giranton; Christian Dumas; Thierry Gaude; J. Mark Cock

1999-01-01

33

Glucocorticoid receptor gene polymorphism and juvenile idiopathic arthritis  

Microsoft Academic Search

BACKGROUND: The glucocorticoid receptor gene (NR3C1) has been suggested as a candidate gene affecting juvenile idiopathic arthritis (JIA) course and prognosis. The purpose of this study is to investigate the glucocorticoid receptor gene BclI polymorphism (rs41423247) in JIA patients, the gene's role in susceptibility to juvenile idiopathic arthritis, and its associations with JIA activity, course and bone mineralization. METHODS: One

Mikhail M Kostik; Alexandra A Klyushina; Mikhail V Moskalenko; Larisa A Scheplyagina; Valentina I Larionova

2011-01-01

34

Genetic Variation in Genes for Host Resistance to Disease Genomic variation is clearly a major factor in host resistance to pathogens in mammals including cattle and humans. Identification  

E-print Network

factor in host resistance to pathogens in mammals including cattle and humans. Identification of specific-initiated epidemics, and to developing models of human gene/pathogen interaction. The cattle genome project has resistance to specific pathogens. Specific genes targeted include the Toll-like receptor (TLR) gene family

35

Effect of glucocorticoid receptor gene polymorphisms on asthma phenotypes.  

PubMed

The clinical presentation of asthma results from complex gene-gene and gene-environment interactions. The natural variability of the DNA sequence within the NR3C1 gene affects the activity of glucocorticoid receptors (GCRs). The NR3C1 gene is localized on chromosome 5q31-q32. The gene coding for the GCR comprises nine exons. The structural domains of the GCR determine the biological functions of the functional domains. The observed resistance to glucocorticosteroids and the normal metabolic profile of Tth111I single nucleotide polymorphism (SNP) carriers is due to the ER22/23EK polymorphism that is present in them. BclI polymorphism significantly affects the process of alternative NR3C1 gene splicing and within that mechanism increases the sensitivity to glucocorticoids (GCs). A total of 451 subjects were enrolled in the present study, including 235 qualified to the group of bronchial asthma patients. A group of 216 healthy participants with no history of asthma or atopic conditions was qualified for the study. Genotyping was accomplished using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR-high resolution melting (HRM) methods. No statistically significant differences were observed in the frequency of Tth111I, BclI and ER22/23EK polymorphisms of the NR3C1 gene when comparing mild, moderate and severe asthma vs. the control group. Investigative analyses demonstrated statistically significant correlations for alleles and genotypes of Tth111I polymorphism of the NR3C1 gene between healthy subjects and patients with severe asthma characterized by a control profile corresponding to an Asthma Control Test (ACT)™ score ?20. It was established that only the Tth111I polymorphism of the NR3C1 gene plays an important role in the pathogenesis of chronic bronchitis leading to the development of asthma with both allergic and non-allergic etiology. PMID:23407653

Panek, Micha?; Pietras, Tadeusz; Fabijan, Artur; Mi?anowski, Maciej; Wieteska, Lukasz; Górski, Pawe?; Kuna, Piotr; Szemraj, Janusz

2013-02-01

36

Carbon dioxide receptor genes in cotton bollworm Helicoverpa armigera.  

PubMed

Carbon dioxide (CO2) is important in insect ecology, eliciting a range of behaviours across different species. Interestingly, the numbers of CO2 gustatory receptors (GRs) vary among insect species. In the model organism Drosophila melanogaster, two GRs (DmelGR21a and DmelGR63a) have been shown to detect CO2. In the butterfly, moth, beetle and mosquito species studied so far, three CO2 GR genes have been identified, while in tsetse flies, four CO2 GR genes have been identified. In other species including honeybees, pea aphids, ants, locusts and wasps, no CO2 GR genes have been identified from the genome. These genomic differences may suggest different mechanisms for CO2 detection exist in different insects but, with the exception of Drosophila and mosquitoes, limited attention has been paid to the CO2 GRs in insects. Here, we cloned three putative CO2 GR genes from the cotton bollworm Helicoverpa armigera and performed phylogenetic and expression analysis. All three H. armigera CO2 GRs (HarmGR1, HarmGR2 and HarmGR3) are specifically expressed in labial palps, the CO2-sensing tissue of this moth. HarmGR3 is significantly activated by NaHCO3 when expressed in insect Sf9 cells but HarmGR1 and HarmGR2 are not. This is the first report characterizing the function of lepidopteran CO2 receptors, which contributes to our general understanding of the molecular mechanisms of insect CO2 gustatory receptors. PMID:25724420

Xu, Wei; Anderson, Alisha

2015-04-01

37

Carbon dioxide receptor genes in cotton bollworm Helicoverpa armigera  

NASA Astrophysics Data System (ADS)

Carbon dioxide (CO2) is important in insect ecology, eliciting a range of behaviours across different species. Interestingly, the numbers of CO2 gustatory receptors (GRs) vary among insect species. In the model organism Drosophila melanogaster, two GRs (DmelGR21a and DmelGR63a) have been shown to detect CO2. In the butterfly, moth, beetle and mosquito species studied so far, three CO2 GR genes have been identified, while in tsetse flies, four CO2 GR genes have been identified. In other species including honeybees, pea aphids, ants, locusts and wasps, no CO2 GR genes have been identified from the genome. These genomic differences may suggest different mechanisms for CO2 detection exist in different insects but, with the exception of Drosophila and mosquitoes, limited attention has been paid to the CO2 GRs in insects. Here, we cloned three putative CO2 GR genes from the cotton bollworm Helicoverpa armigera and performed phylogenetic and expression analysis. All three H. armigera CO2 GRs (HarmGR1, HarmGR2 and HarmGR3) are specifically expressed in labial palps, the CO2-sensing tissue of this moth. HarmGR3 is significantly activated by NaHCO3 when expressed in insect Sf9 cells but HarmGR1 and HarmGR2 are not. This is the first report characterizing the function of lepidopteran CO2 receptors, which contributes to our general understanding of the molecular mechanisms of insect CO2 gustatory receptors.

Xu, Wei; Anderson, Alisha

2015-04-01

38

Diverse growth hormone receptor gene mutations in Laron syndrome  

SciTech Connect

To better understand the molecular genetic basis and genetic epidemiology of Laron syndrome (growth-hormone insensitivity syndrome), the authors analysed the growth-hormone receptor (GHR) genes of seven unrelated affected individuals from the United States, South America, Europe, and Africa. They amplified all nine GHR gene exons and splice junctions from these individuals by PCR and screened the products for mutations by using denaturing gradient gel electrophoresis (DGGE). They identified a single GHR gene fragment with abnormal DGGE results for each affected individual, sequenced this fragment, and, in each case, identified a mutation likely to cause Laron syndrome, including two nonsense mutations (R43X and R217X), two splice-junction mutations, (189-1 G to T and 71+1 G to A), and two frameshift mutations (46 del TT and 230 del TA or AT). Only one of these mutations, R43X, has been previously reported. Using haplotype analysis, they determined that this mutation, which involves a CpG dinucleotide hot spot, likely arose as a separate event in this case, relative to the two prior reports of R43X. Aside from R43X, the mutations identified are unique to patients from particular geographic regions. Ten GHR gene mutations have now been described in this disorder. The authors conclude that Laron syndrome is caused by diverse GHR gene mutations, including deletions, RNA processing defects, translational stop codons, and missense codons. All the identified mutations involve the extracellular domain of the receptor, and most are unique to particular families or geographic areas. 35 refs., 3 figs., 1 tab.

Berg, M.A.; Francke, U. (Stanford Univ. School of Medicine, CA (United States)); Gracia, R.; Rosenbloom, A.; Toledo, S.P.A. (Univ. Autonoma, Madrid (Spain)); Chernausek, S. (Children's Hospital Medical Center, Cincinnati, OH (United States)); Guevara-Aguirre, J. (Institute of Endocrinology, Metabolism, and Reproduction, Quito (Ecuador)); Hopp, M. (Univ. of Witwatersrand, Johannesburg (South Africa)); Rosenbloom, A.; Argente, J. (Univ. of Florida, Gainesville (United States)); Toledo, S.P.A. (Univ. of Sao Paulo (Brazil))

1993-05-01

39

Gene Transfer and Molecular Cloning of the Human NGF Receptor  

NASA Astrophysics Data System (ADS)

Nerve growth factor (NGF) and its receptor are important in the development of cells derived from the neural crest. Mouse L cell transformants have been generated that stably express the human NGF receptor gene transfer with total human DNA. Affinity cross-linking, metabolic labeling and immunoprecipitation, and equilibrium binding with 125I-labeled NGF revealed that this NGF receptor had the same size and binding characteristics as the receptor from human melanoma cells and rat PC12 cells. The sequences encoding the NGF receptor were molecularly cloned using the human Alu repetitive sequence as a probe. A cosmid clone that contained the human NGF receptor gene allowed efficient transfection and expression of the receptor.

Chao, Moses V.; Bothwell, Mark A.; Ross, Alonzo H.; Koprowski, Hilary; Lanahan, Anthony A.; Buck, C. Randall; Sehgal, Amita

1986-04-01

40

Regulation of cytochrome P450 (CYP) genes by nuclear receptors.  

PubMed Central

Members of the nuclear-receptor superfamily mediate crucial physiological functions by regulating the synthesis of their target genes. Nuclear receptors are usually activated by ligand binding. Cytochrome P450 (CYP) isoforms often catalyse both formation and degradation of these ligands. CYPs also metabolize many exogenous compounds, some of which may act as activators of nuclear receptors and disruptors of endocrine and cellular homoeostasis. This review summarizes recent findings that indicate that major classes of CYP genes are selectively regulated by certain ligand-activated nuclear receptors, thus creating tightly controlled networks. PMID:10749660

Honkakoski, P; Negishi, M

2000-01-01

41

Dysregulation of gene expression within the peroxisome proliferator activated receptor pathway in morbidly obese patients  

Microsoft Academic Search

BACKGROUND: The causes of obesity are multifactorial but may include dysregulation of a family of related genes, such as the peroxisome proliferator activated receptor gamma (PPARgamma). When activated, the PPARgamma pathway promotes lipid metabolism. This study used microarray technology to evaluate differential gene expression profiles in obese patients undergoing bariatric surgery. METHODS: The study enrolled six morbidly obese patients with

A. Katharine Hindle; Jadd Koury; Tim McCaffrey; Sidney W. Fu; Fred Brody

2009-01-01

42

Nuclear Receptor Coactivators Modulate Hormone-Dependent Gene Expression in Brain and Female  

E-print Network

Nuclear Receptor Coactivators Modulate Hormone- Dependent Gene Expression in Brain and Female- crinology 143: 436­444, 2002) STEROID HORMONES ARE essential for growth, devel- opment, and reproduction in a variety of hormone-responsive tissues, including brain (14­17). This ER-dependent induction of PR gene

43

Identification of chemosensory receptor genes from vertebrate genomes.  

PubMed

Chemical senses are essential for the survival of animals. In vertebrates, mainly three different types of receptors, olfactory receptors (ORs), vomeronasal receptors type 1 (V1Rs), and vomeronasal receptors type 2 (V2Rs), are responsible for the detection of chemicals in the environment. Mouse or rat genomes contain >1,000 OR genes, forming the largest multigene family in vertebrates, and have >100 V1R and V2R genes as well. Recent advancement in genome sequencing enabled us to computationally identify nearly complete repertories of OR, V1R, and V2R genes from various organisms, revealing that the numbers of these genes are highly variable among different organisms depending on each species' living environment. Here I would explain bioinformatic methods to identify the entire repertoires of OR, V1R, and V2R genes from vertebrate genome sequences. PMID:24014356

Niimura, Yoshihito

2013-01-01

44

Extraordinary Diversity of Chemosensory Receptor Gene Repertoires Among Vertebrates  

E-print Network

of each gene has about 1,000 nucleotides. They are mainly expressed in sensory neurons of MOEsExtraordinary Diversity of Chemosensory Receptor Gene Repertoires Among Vertebrates P. Shi and J that are encoded by several large gene families. This review summarizes recent comparative genomic and evolutionary

Zhang, Jianzhi

45

Ontogeny of Odorant Receptor Gene Expression in Zebrafish, Danio rerio  

E-print Network

of neurons expressing OR genes through a developmental progression from embryo (12 h postfertilization receptors, zebrafish, placode, olfac- tory neuron, gene expression. 01996John Wiley &Sons,Inc. INTRODUCTION;Ben-Arieet al., 1994)down to 100 in catfish (Ngai et al., 1993b). Neurons expressing specific OR genes

Vogt, Richard G.

46

Profiling of olfactory receptor gene expression in whole human olfactory mucosa.  

PubMed

Olfactory perception is mediated by a large array of olfactory receptor genes. The human genome contains 851 olfactory receptor gene loci. More than 50% of the loci are annotated as nonfunctional due to frame-disrupting mutations. Furthermore haplotypic missense alleles can be nonfunctional resulting from substitution of key amino acids governing protein folding or interactions with signal transduction components. Beyond their role in odor recognition, functional olfactory receptors are also required for a proper targeting of olfactory neuron axons to their corresponding glomeruli in the olfactory bulb. Therefore, we anticipate that profiling of olfactory receptor gene expression in whole human olfactory mucosa and analysis in the human population of their expression should provide an opportunity to select the frequently expressed and potentially functional olfactory receptors in view of a systematic deorphanization. To address this issue, we designed a TaqMan Low Density Array (Applied Biosystems), containing probes for 356 predicted human olfactory receptor loci to investigate their expression in whole human olfactory mucosa tissues from 26 individuals (13 women, 13 men; aged from 39 to 81 years, with an average of 67±11 years for women and 63±12 years for men). Total RNA isolation, DNase treatment, RNA integrity evaluation and reverse transcription were performed for these 26 samples. Then 384 targeted genes (including endogenous control genes and reference genes specifically expressed in olfactory epithelium for normalization purpose) were analyzed using the same real-time reverse transcription PCR platform. On average, the expression of 273 human olfactory receptor genes was observed in the 26 selected whole human olfactory mucosa analyzed, of which 90 were expressed in all 26 individuals. Most of the olfactory receptors deorphanized to date on the basis of sensitivity to known odorant molecules, which are described in the literature, were found in the expressed olfactory receptors gene set. PMID:24800820

Verbeurgt, Christophe; Wilkin, Françoise; Tarabichi, Maxime; Gregoire, Françoise; Dumont, Jacques E; Chatelain, Pierre

2014-01-01

47

Profiling of Olfactory Receptor Gene Expression in Whole Human Olfactory Mucosa  

PubMed Central

Olfactory perception is mediated by a large array of olfactory receptor genes. The human genome contains 851 olfactory receptor gene loci. More than 50% of the loci are annotated as nonfunctional due to frame-disrupting mutations. Furthermore haplotypic missense alleles can be nonfunctional resulting from substitution of key amino acids governing protein folding or interactions with signal transduction components. Beyond their role in odor recognition, functional olfactory receptors are also required for a proper targeting of olfactory neuron axons to their corresponding glomeruli in the olfactory bulb. Therefore, we anticipate that profiling of olfactory receptor gene expression in whole human olfactory mucosa and analysis in the human population of their expression should provide an opportunity to select the frequently expressed and potentially functional olfactory receptors in view of a systematic deorphanization. To address this issue, we designed a TaqMan Low Density Array (Applied Biosystems), containing probes for 356 predicted human olfactory receptor loci to investigate their expression in whole human olfactory mucosa tissues from 26 individuals (13 women, 13 men; aged from 39 to 81 years, with an average of 67±11 years for women and 63±12 years for men). Total RNA isolation, DNase treatment, RNA integrity evaluation and reverse transcription were performed for these 26 samples. Then 384 targeted genes (including endogenous control genes and reference genes specifically expressed in olfactory epithelium for normalization purpose) were analyzed using the same real-time reverse transcription PCR platform. On average, the expression of 273 human olfactory receptor genes was observed in the 26 selected whole human olfactory mucosa analyzed, of which 90 were expressed in all 26 individuals. Most of the olfactory receptors deorphanized to date on the basis of sensitivity to known odorant molecules, which are described in the literature, were found in the expressed olfactory receptors gene set. PMID:24800820

Tarabichi, Maxime; Gregoire, Françoise; Dumont, Jacques E.; Chatelain, Pierre

2014-01-01

48

First evidence for functional vomeronasal 2 receptor genes in primates.  

PubMed

Two classes of vomeronasal receptor genes, V1R and V2R, occur in vertebrates. Whereas, V1R loci are found in a wide variety of mammals, including primates, intact V2R genes have thus far only been described in rodents and marsupials. In primates, the V2R repertoire has been considered degenerate. Here, we identify for the first time two intact V2R loci in a strepsirrhine primate, the grey mouse lemur (Microcebus murinus), and demonstrate their expression in the vomeronasal organ. Putatively functional orthologues are present in two other strepsirrhines, whereas, both loci are pseudogenes in a range of anthropoid species. The functional significance of the loci is unknown, but positive selection on one of them is consistent with an adaptive role in pheromone detection. Finally, conservation of V2R loci in strepsirrhines is notable, given their high diversity and role in MUP and MHC detection in rodents. PMID:23269843

Hohenbrink, Philipp; Mundy, Nicholas I; Zimmermann, Elke; Radespiel, Ute

2013-02-23

49

Constraint and Adaptation in newt Toll-Like Receptor Genes  

PubMed Central

Acute die-offs of amphibian populations worldwide have been linked to the emergence of viral and fungal diseases. Inter and intraspecific immunogenetic differences may influence the outcome of infection. Toll-like receptors (TLRs) are an essential component of innate immunity and also prime acquired defenses. We report the first comprehensive assessment of TLR gene variation for urodele amphibians. The Lissotriton newt TLR repertoire includes representatives of 13 families and is compositionally most similar to that of the anuran Xenopus. Both ancient and recent gene duplications have occurred in urodeles, bringing the total number of TLR genes to at least 21. Purifying selection has predominated the evolution of newt TLRs in both long (?70 Ma) and medium (?18 Ma) timescales. However, we find evidence for both purifying and positive selection acting on TLRs in two recently diverged (2–5 Ma) allopatric evolutionary lineages (Lissotriton montandoni and L. vulgaris graecus). Overall, both forms of selection have been stronger in L. v. graecus, while constraint on most TLR genes in L. montandoni appears relaxed. The differences in selection regimes are unlikely to be biased by demographic effects because these were controlled by means of a historical demographic model derived from an independent data set of 62 loci. We infer that TLR genes undergo distinct trajectories of adaptive evolution in closely related amphibian lineages, highlight the potential of TLRs to capture the signatures of different assemblages of pathogenic microorganisms, and suggest differences between lineages in the relative roles of innate and acquired immunity. PMID:25480684

Babik, Wies?aw; Dudek, Katarzyna; Fijarczyk, Anna; Pabijan, Maciej; Stuglik, Micha?; Szkotak, Rafa?; Zieli?ski, Piotr

2015-01-01

50

The ?3 subunit gene of the nicotinic acetylcholine receptor is a candidate gene for ethanol stimulation  

PubMed Central

Alcohol and nicotine are coabused, and preclinical and clinical data suggest that common genes may influence responses to both drugs. A gene in a region of mouse chromosome 9 that includes a cluster of three nicotinic acetylcholine receptor (nAChR) subunit genes influences the locomotor stimulant response to ethanol. The current studies first used congenic mice to confirm the influential gene on chromosome 9. Congenic F2 mice were then used to more finely map the location. Gene expression of the three subunit genes was quantified in strains of mice that differ in response to ethanol. Finally, the locomotor response to ethanol was examined in mice heterozygous for a null mutation of the ?3 nAChR subunit gene (Chrna3). Congenic data indicate that a gene on chromosome 9, within a 46 cM region that contains the cluster of nAChR subunit genes, accounts for 41% of the genetic variation in the stimulant response to ethanol. Greater expression of Chrna3 was found in whole brain and dissected brain regions relevant to locomotor behavior in mice that were less sensitive to ethanol-induced stimulation compared to mice that were robustly stimulated; the other two nAChR subunit genes in the gene cluster (?5 and ?4) were not differentially expressed. Locomotor stimulation was not expressed on the genetic background of Chrna3 heterozygous (+/?) and wild-type (+/+) mice; +/? mice were more sensitive than +/+ mice to the locomotor depressant effects of ethanol. Chrna3 is a candidate gene for the acute locomotor stimulant response to ethanol that deserves further examination. PMID:18826434

Kamens, H. M.; McKinnon, C. S.; Li, N; Helms, M. L.; Belknap, J. K.; Phillips, T. J.

2009-01-01

51

Adenovirus receptors and their implications in gene delivery  

PubMed Central

Adenoviruses (Ads) have gained popularity as gene delivery vectors for therapeutic and prophylactic applications. Ad entry into host cells involves specific interactions between cell surface receptors and viral capsid proteins. Several cell surface molecules have been identified as receptors for Ad attachment and entry. Tissue tropism of Ad vectors is greatly influenced by their receptor usage. A variety of strategies have been investigated to modify Ad vector tropism by manipulating the receptor-interacting moieties. Many such strategies are aimed at targeting and/or detargeting of Ad vectors. In this review, we discuss the various cell surface molecules that are implicated as receptors for virus attachment and internalization. Special emphasis is given to Ad types that are utilized as gene delivery vectors. Various strategies to modify Ad tropism using the knowledge of Ad receptors are also discussed. PMID:19647886

Sharma, Anurag; Li, Xiaoxin; Bangari, Dinesh S.; Mittal, Suresh K.

2010-01-01

52

Modulation of oestrogen action by receptor gene inhibition  

Microsoft Academic Search

Selective oestrogen receptor downregulators (SERDs) are a class of highly effective steroidal antitumour agents that reduce cellular levels of the oestrogen receptor (ER). In this study, we compared the efficacy by which three novel molecular approaches: (1) antisense oligonucleotides; (2) antisense RNA; and (3) dominant negative mutants are able to act as SERDs. Using transient and, where appropriate, stable gene

T. A. Madden; D. Barrow; R. A. McClelland; J. M. W. Gee; R. I. Nicholson

2000-01-01

53

Androgen Receptor Repression of GnRH Gene Transcription  

E-print Network

Androgen Receptor Repression of GnRH Gene Transcription Melissa J. Brayman, Patricia A. Pepa, Sara the GnRH regulatory region in the GT1-7 cell line, a model of GnRH neurons. A synthetic androgen, R1881 to colo- calize steroid receptors with GnRH-expressing neurons, it was believed that this feedback

Mellon, Pamela L.

54

Deletion of Exon 15 of the LDL Receptor Gene Is Associated With a Mild Form of Familial Hypercholesterolemia FH-Espoo  

Microsoft Academic Search

We describe a mutation of the low-density lipoprotein (LDL) receptor gene, designated familial hypercholesterolemia (FH)-Espoo, which deletes exon 15 of the LDL receptor gene. The mutant receptor is predicted to lack 57 amino acids, including 18 serine and threonine residues, which are the sites of the clustered 0-linked sugars of the receptor. Studies on 10 carriers of this gene revealed

Pekka V. I. Koivisto; Ulla-Maija Koivisto; Petri T. Kovanen; Helena Gylling; Tatu A. Miettinen; Kimmo Kontula

55

Identification of Receptor-Tyrosine-Kinase-Signaling Target Genes Reveals Receptor-Specific Activities and Pathway Branchpoints During Drosophila Development  

PubMed Central

Receptor tyrosine kinases (RTKs) are an important family of signaling molecules with the unusual property that they are able to transduce their signals using the same downstream pathways. This has led to an unresolved debate as to whether individual receptors are interchangeable, or if each receptor can mediate specific downstream responses. To address this question, we have conducted a screen to identify target genes whose expression is differentially modulated by RTKs and their downstream pathway components. Using whole-mount in situ hybridization in Drosophila embryos exposed to constitutively active RTK pathway signaling, along with quantitative RT–PCR, we found that a significant fraction of target genes respond differentially in a spatial and/or quantitative manner. This includes differential responses to EGF receptor vs. fibroblast growth factor receptor signaling as well as to more downstream components such as Ras1 and pointed. We show that not only genes but also individual alternative transcripts can respond differently to signaling, and we present evidence that the differential responses can be mediated at the transcriptional level. Our results demonstrate that different RTKs can elicit distinct transcriptional responses, and the target genes obtained from our screen provide a valuable resource for further exploration of the mechanisms underlying this signaling specificity. PMID:19189950

Leatherbarrow, John R.; Halfon, Marc S.

2009-01-01

56

Multimodality Imaging of Gene Transfer with a Receptor-Based Reporter Gene  

E-print Network

Multimodality Imaging of Gene Transfer with a Receptor-Based Reporter Gene Ron Chen1, Jesse J, Missouri Gene therapy trials have traditionally used tumor and tissue biopsies for assessing the efficacy of gene transfer. Non- invasive imaging techniques offer a distinct advantage over tissue biopsies

Larson-Prior, Linda

57

Characterization of avian T-cell receptor ??genes  

PubMed Central

In birds and mammals T cells develop along two discrete pathways characterized by expression of either the ?? or the ?? T-cell antigen receptors (TCRs). To gain further insight into the evolutionary significance of the ?? T-cell lineage, the present studies sought to define the chicken TCR? locus. A splenic cDNA library was screened with two polymerase chain reaction products obtained from genomic DNA using primers for highly conserved regions of TCR and immunoglobulin genes. This strategy yielded cDNA clones with characteristics of mammalian TCR ? chains, including canonical residues considered important for proper folding and stability. Northern blot analysis with the TCR? cDNA probe revealed 1.9-kb transcripts in the thymus, spleen, and a ?? T-cell line, but not in B or ?? T-cell lines. Three multimember V? subfamilies, three J? gene segments, and a single constant region C? gene were identified in the avian TCR? locus. Members of each of the three V? subfamilies were found to undergo rearrangement in parallel during the first wave of thymocyte development. TCR? repertoire diversification was initiated on embryonic day 10 by an apparently random pattern of V-J? recombination, nuclease activity, and P- and N-nucleotide additions to generate a diverse repertoire of avian TCR? genes early in ontogeny. PMID:8986811

Six, Adrien; Rast, Jonathan?P.; McCormack, Wayne?T.; Dunon, Dominique; Courtois, David; Li, Yue; Chen, Chen-lo?H.; Cooper, Max?D.

1996-01-01

58

Regulation of the Oct-4 gene by nuclear receptors.  

PubMed Central

To unravel the network of transcription factors established during development it is important to understand how genes specifically expressed during embryogenesis are regulated. Oct-4 is a transcription factor whose expression is associated with an undifferentiated cell phenotype in the early mouse embryo and is downregulated when such cells differentiate. An enhancer in the upstream region of Oct-4 has previously been reported as being sufficient to mediate the cell-type specific expression and RA-dependent down-regulation in EC cells, although the enhancer contains no retinoic acid receptor (RAR) binding sites. Here we report the identification of promoter elements important for the regulation of the Oct-4 gene in EC cells. A region of the proximal Oct-4 promoter contains an overlapping set of regulatory elements including a high affinity binding site for Sp1 and three direct repeats of an AGGTCA-like sequence with either +1 or 0 spacing. Binding and transient transfection assays reveal that Oct-4 is subject to negative regulation by different members of the steroid-thyroid hormone receptor superfamily. Specifically, important roles for ARP-1 and RAR in Oct-4 expression are indicated. Images PMID:8152920

Sylvester, I; Schöler, H R

1994-01-01

59

A mutation in the thyroid hormone receptor alpha gene.  

PubMed

Thyroid hormones exert their effects through alpha (TR?1) and beta (TR?1 and TR?2) receptors. Here we describe a child with classic features of hypothyroidism (growth retardation, developmental retardation, skeletal dysplasia, and severe constipation) but only borderline-abnormal thyroid hormone levels. Using whole-exome sequencing, we identified a de novo heterozygous nonsense mutation in a gene encoding thyroid hormone receptor alpha (THRA) and generating a mutant protein that inhibits wild-type receptor action in a dominant negative manner. Our observations are consistent with defective human TR?-mediated thyroid hormone resistance and substantiate the concept of hormone action through distinct receptor subtypes in different target tissues. PMID:22168587

Bochukova, Elena; Schoenmakers, Nadia; Agostini, Maura; Schoenmakers, Erik; Rajanayagam, Odelia; Keogh, Julia M; Henning, Elana; Reinemund, Jana; Gevers, Evelien; Sarri, Margarita; Downes, Kate; Offiah, Amaka; Albanese, Assunta; Halsall, David; Schwabe, John W R; Bain, Murray; Lindley, Keith; Muntoni, Francesco; Vargha-Khadem, Faraneh; Khadem, Faraneh Vargha; Dattani, Mehul; Farooqi, I Sadaf; Gurnell, Mark; Chatterjee, Krishna

2012-01-19

60

Characteristics of the mouse genomic histamine H1 receptor gene  

SciTech Connect

We report here the molecular cloning of a mouse histamine H1 receptor gene. The protein deduced from the nucleotide sequence is composed of 488 amino acid residues with characteristic properties of GTP binding protein-coupled receptors. Our results suggest that the mouse histamine H1 receptor gene is a single locus, and no related sequences were detected. Interspecific backcross analysis indicated that the mouse histamine H1 receptor gene (Hrh1) is located in the central region of mouse Chromosome 6 linked to microphthalmia (Mitfmi), ras-related fibrosarcoma oncogene 1 (Raf1), and ret proto-oncogene (Ret) in a region of homology with human chromosome 3p. 12 refs., 3 figs.

Inoue, Isao; Taniuchi, Ichiro; Kitamura, Daisuke [Kyushu Univ., Fukuoka (Japan)] [and others] [Kyushu Univ., Fukuoka (Japan); and others

1996-08-15

61

Identification of a null mutation in the human dopamine D4 receptor gene  

SciTech Connect

Dopamine receptors belong to the family of G protein-coupled receptors. Five different dopamine receptor genes have thus far been identified. These receptors are classified into two main subfamilies: D1, which includes the D1 and D5 receptors, and D2, which includes the D2, D3, and D4 receptors. The dopamine D4 receptor is of great interest for research into neuropsychiatric disorders and psychopharmacology in light of the fact that it binds the antipsychotic medication clozapine with higher affinity than does any other dopamine receptor. In addition, among the dopamine receptors, the D4 receptor shows a uniquely high degree of genetic variation in the human population. We identified a new 13 bp deletion in exon 1 of the D4 gene. This frameshift creates a terminator codon at amino acid position 98. mRNA isolated from brain tissue of two heterozygous persons showed both alleles to be expressed. The deletion occurs with a frequency of 2% in the German population. One person was identified to be homozygous for the deletion. Interestingly, he has a normal intelligence and did not exhibit a major psychiatric disorder as defined by DSM III-R. The 13 bp deletion is the first mutation resulting in premature translation termination reported for a dopamine receptor gene so far. This mutation is a good candidate to test for potential effects on disease and/or individual response to pharmacotherapy. Association studies in patients with various psychiatric illnesses and differences in response to clozapine are underway.

Noethen, M.M.; Cichon, S. [Univ. of Bonn (Georgia); Hebebrand, J. [Univ. of Marburg (Georgia)] [and others

1994-09-01

62

Dopamine D4 Receptor Gene: Novelty or Nonsense?  

Microsoft Academic Search

Although the role of genetics in personality has been studied extensively at a phenomenological level, only lately has the investigation of specific genes been performed. Recent reports suggest that DNA variants of the dopamine D4 receptor gene (DRD4) are associated with the personality trait of novelty seeking; however, others fail to replicate this finding. Such conflicting results suggest either a

Andrew D Paterson; Glen A Sunohara; James L Kennedy

1999-01-01

63

Melanoma risk is associated with vitamin D receptor gene polymorphisms.  

PubMed

Previous studies have reported that vitamin D receptor (VDR) gene polymorphisms are associated with the occurrence of various cancers, including melanoma. The aim of the current study was to investigate the association of VDR gene polymorphisms with melanoma risk, clinicopathological characteristics, and vitamin D levels. The study group included 117 patients (84 patients with superficial spreading melanoma and 33 patients with nodular melanoma). The control group included 122 sex-matched and age-matched healthy-blood donors of the same ethnicity. VDR gene polymorphisms FokI, EcoRV, TaqI, and ApaI were genotyped by real-time PCR. In 60 patients, the total 25-hydroxyvitamin D levels were evaluated in serum samples by direct chemiluminescence. Associations among parameters were considered to be significant if the P value was less than 0.05. Significant differences in the frequencies of VDR genotypes were observed between cases and the control group for FokI and TaqI polymorphisms (P<0.0001; P=0.005, respectively). Heterozygous Ff as well as mutant FF genotypes of the FokI polymorphism were associated with increased melanoma risk compared with the wild-type form [odds ratio (OR)=3.035, P=0.003; OR=9.276, P<0.0001, respectively]. A significantly increased melanoma risk was observed for the heterozygous Tt (OR=2.302, P=0.011) and the mutated variant tt (OR=3.697, P=0.003) of the TaqI polymorphism in comparison with the wild-type genotype. None of the polymorphisms studied was associated with clinicopathological characteristics and vitamin D serum level. Our results suggest that FokI and TaqI polymorphisms in the VDR gene may be considered as potential biomarkers for melanoma susceptibility. Low vitamin D levels in melanoma patients indicate the need for vitamin D supplementation. PMID:24638155

Zeljic, Katarina; Kandolf-Sekulovic, Lidija; Supic, Gordana; Pejovic, Janko; Novakovic, Marijan; Mijuskovic, Zeljko; Magic, Zvonko

2014-06-01

64

Structure and expression of the mouse growth hormone receptor\\/growth hormone binding protein gene  

Microsoft Academic Search

The mouse growth hormone receptor\\/growth hormone-binding protein (GHR\\/BP) gene produces several distinct mRNA forms through alterna- tive splicing, including mRNAs encoding the membrane-bound growth hormone receptor (GHR) and the soluble growth hormone-binding protein (GHBP). Transcripts are also heterogeneous in their 5* regions due to alternative selection of two major 5* untranslated region (5*UTR) sequences, designated L1 and L2. Here we

J. Moffat; F Talamantes

1999-01-01

65

Structure of the bovine ETB endothelin receptor gene.  

PubMed Central

The structure of the gene encoding the bovine type B endothelin receptor (ETB) has been established and compared with those of other heptahelical receptors. The gene is present as a single copy in the bovine genome, as demonstrated by Southern blot analysis, and spans at least 36 kb. The coding region is divided into 7 exons separated by 6 introns, one of which is more than 23 kb in length. The exons correspond well to the structural domains of the receptor: the first exon encodes the first and second transmembrane domains, and each of the following transmembrane domains is encoded by a separate exon. The portion of the ETB protein sequence encoded by exon 3 is quite different from the corresponding ETA sequence, suggesting that this region is responsible for the distinct ligand specificities of the two receptor subtypes. The second intron interrupts the canonical Asp-Arg-Tyr sequence, which is located at the end of the third transmembrane domain of the heptahelical receptors, as with the substance P, substance K, dopamine D2 and dopamine D3 receptor genes. To map the 5' region of the gene and determine the start of transcription, primer-extended cDNAs were cloned and sequenced: multiple start sites were deduced with no apparent TATA box in the expected upstream region. Similar results were obtained by ribonuclease protection analysis. Images Fig. 4. Fig. 5. PMID:1417782

Mizuno, T; Saito, Y; Itakura, M; Ito, F; Ito, T; Moriyama, E N; Hagiwara, H; Hirose, S

1992-01-01

66

Odorant receptor genes are expressed in olfactory neuroblastoma.  

PubMed

Olfactory neuroblastoma (ONB) is a malignant tumor found in the human nasal cavity. These tumors are rare and poorly characterized at the molecular level. In this study, we asked whether olfactory-specific genes are expressed in ONBs by using reverse-transcriptase-polymerase chain reaction. We found that the olfactory marker protein and the RIC-8B genes, which are specifically expressed in mature olfactory neurons, are expressed in ONBs. Importantly, we also found that ONBs express a large variety of odorant receptor genes, representative of different odorant receptor gene subfamilies. Our results show that the ONBs express genes that are normally expressed in mature olfactory neurons and indicate that they are derived from progenitor or immature cells in the olfactory epithelium and not from a clonal expansion of a single or few mature olfactory neurons. PMID:24065686

Gonzalez-Kristeller, D C; Gutiyama, L M; Campos, A H; Soares, F A; Brentani, H; Malnic, B

2013-01-01

67

Sulfotransferase genes: Regulation by nuclear receptors in response to xeno/endo-biotics  

PubMed Central

Pregnane X receptor (PXR) and constitutive active/androstane receptor (CAR), members of the nuclear receptor superfamily, are two major xeno-sensing transcription factors. They can be activated by a broad range of lipophilic xenobiotics including therapeutics drugs. In addition to xenobiotics, endogenous compounds such as steroid hormones and bile acids can also activate PXR and/or CAR. These nuclear receptors regulate genes that encode enzymes and transporters that metabolize and excrete both xenobiotics and endobiotics. Sulfotransferases (SULTs) are a group of these enzymes and sulfate xenobiotics for detoxification. In general, inactivation by sulfation constitutes the mechanism to maintain homeostasis of endobiotics. Thus, deciphering the molecular mechanism by which PXR and CAR regulate SULT genes is critical for understanding the roles of SULTs in the alterations of physiological and pathophysiological processes caused by drug treatment or environmental exposures. PMID:24025090

Kodama, Susumu; Negishi, Masahiko

2014-01-01

68

Integrating nuclear receptor mobility in models of gene regulation  

PubMed Central

The mode of action of nuclear receptors in living cells is an actively investigated field but much remains hypothetical due to the lack, until recently, of methods allowing the assessment of molecular mechanisms in vivo. However, these last years, the development of fluorescence microscopy methods has allowed initiating the dissection of the molecular mechanisms underlying gene regulation by nuclear receptors directly in living cells or organisms. Following our analyses on peroxisome proliferator activated receptors (PPARs) in living cells, we discuss here the different models arising from the use of these tools, that attempt to link mobility, DNA binding or chromatin interaction, and transcriptional activity. PMID:16741568

Gelman, Laurent; Feige, Jerome N.; Tudor, Cicerone; Engelborghs, Yves; Wahli, Walter; Desvergne, Beatrice

2006-01-01

69

Chromosomal localization of the human prostanoid receptor gene family  

SciTech Connect

Prostaglandins (PGD{sub 2}, PGE{sub 2}, PGF{sub 2{alpha}}, and PGI{sub 2}) and thromboxane A{sub 2} (TXA{sub 2}) are biologically active molecules derived from the metabolism of arachidonic acid by cyclooxygenases. They produce a wide variety of physiological and pathophysiological effects mediated through specific G protein-coupled cell surface receptors. In this study, we have mapped the chromosomal positions of the human genes that encode the PGE{sub 2} receptor subtypes (PTGER1, PTGER2, and PTGER3), the PGF{sub 2{alpha}} receptor (PTGFR), the PGI{sub 2} receptor (PTGIR), and the TXA{sub 2} receptor (TBXA2R) using in situ hybridization. The PTGER1, TBXA2R, and PTGIR genes mapped to chromosome 19 at positions 19p13.1, 19p13.3, and 19q13.3, respectively. The PTGFR and PTGER3 genes mapped to chromosome 1 at positions 1p31.1 and 1p31.2, respectively, and PTGER2 gene mapped to chromosome band 5p13.1. 16 refs., 1 tab.

Duncan, A.M.V.; Anderson, L.L. [Queen`s Univ., Kingston, Ontario (Canada)] [Queen`s Univ., Kingston, Ontario (Canada); Funk, C.D. [Vanderbilt Univ., Nashville, TN (United States)] [and others] [Vanderbilt Univ., Nashville, TN (United States); and others

1995-02-10

70

Isolation and characterisation of main olfactory and vomeronasal receptor gene families from the Atlantic salmon (Salmo salar)  

E-print Network

receptor type 1; TM, transmembrane domain; VNO, vomeronasal organ; VNR, vomeronasal receptor geneIsolation and characterisation of main olfactory and vomeronasal receptor gene families from report the isolation and characterisation of salmon olfactory receptor (SOR) and salmon vomeronasal

Neigel, Joseph E.

71

Comparison of the Olfactory Receptor Genes in Canines and Primates  

NSDL National Science Digital Library

Dogs are known for their acute sense of smell. Humans are not. Do dogs have a higher percentage of functional olfactory receptors as compared to humans and other primates? Students will be assigned to obtain the full length genetic sequence of five olfactory receptor (OR) genes from their assigned OR family. (See website below.) Students will determine if a functional orthologous gene is present in the human genome, in the genome of a great ape, and in the sequence of a monkey. The class will pool their data and analyze for the percentage of pseudogenes present in each group.

Gary Ogden (St. Mary's University; )

2005-05-25

72

Natural killer cell receptor genes in the family Equidae: not only Ly49.  

PubMed

Natural killer (NK) cells have important functions in immunity. NK recognition in mammals can be mediated through killer cell immunoglobulin-like receptors (KIR) and/or killer cell lectin-like Ly49 receptors. Genes encoding highly variable NK cell receptors (NKR) represent rapidly evolving genomic regions. No single conservative model of NKR genes was observed in mammals. Single-copy low polymorphic NKR genes present in one mammalian species may expand into highly polymorphic multigene families in other species. In contrast to other non-rodent mammals, multiple Ly49-like genes appear to exist in the horse, while no functional KIR genes were observed in this species. In this study, Ly49 and KIR were sought and their evolution was characterized in the entire family Equidae. Genomic sequences retrieved showed the presence of at least five highly conserved polymorphic Ly49 genes in horses, asses and zebras. These findings confirmed that the expansion of Ly49 occurred in the entire family. Several KIR-like sequences were also identified in the genome of Equids. Besides a previously identified non-functional KIR-Immunoglobulin-like transcript fusion gene (KIR-ILTA) and two putative pseudogenes, a KIR3DL-like sequence was analyzed. In contrast to previous observations made in the horse, the KIR3DL sequence, genomic organization and mRNA expression suggest that all Equids might produce a functional KIR receptor protein molecule with a single non-mutated immune tyrosine-based inhibition motif (ITIM) domain. No evidence for positive selection in the KIR3DL gene was found. Phylogenetic analysis including rhinoceros and tapir genomic DNA and deduced amino acid KIR-related sequences showed differences between families and even between species within the order Perissodactyla. The results suggest that the order Perissodactyla and its family Equidae with expanded Ly49 genes and with a potentially functional KIR gene may represent an interesting model for evolutionary biology of NKR genes. PMID:23724088

Futas, Jan; Horin, Petr

2013-01-01

73

Natural Killer Cell Receptor Genes in the Family Equidae: Not only Ly49  

PubMed Central

Natural killer (NK) cells have important functions in immunity. NK recognition in mammals can be mediated through killer cell immunoglobulin-like receptors (KIR) and/or killer cell lectin-like Ly49 receptors. Genes encoding highly variable NK cell receptors (NKR) represent rapidly evolving genomic regions. No single conservative model of NKR genes was observed in mammals. Single-copy low polymorphic NKR genes present in one mammalian species may expand into highly polymorphic multigene families in other species. In contrast to other non-rodent mammals, multiple Ly49-like genes appear to exist in the horse, while no functional KIR genes were observed in this species. In this study, Ly49 and KIR were sought and their evolution was characterized in the entire family Equidae. Genomic sequences retrieved showed the presence of at least five highly conserved polymorphic Ly49 genes in horses, asses and zebras. These findings confirmed that the expansion of Ly49 occurred in the entire family. Several KIR-like sequences were also identified in the genome of Equids. Besides a previously identified non-functional KIR-Immunoglobulin-like transcript fusion gene (KIR-ILTA) and two putative pseudogenes, a KIR3DL-like sequence was analyzed. In contrast to previous observations made in the horse, the KIR3DL sequence, genomic organization and mRNA expression suggest that all Equids might produce a functional KIR receptor protein molecule with a single non-mutated immune tyrosine-based inhibition motif (ITIM) domain. No evidence for positive selection in the KIR3DL gene was found. Phylogenetic analysis including rhinoceros and tapir genomic DNA and deduced amino acid KIR-related sequences showed differences between families and even between species within the order Perissodactyla. The results suggest that the order Perissodactyla and its family Equidae with expanded Ly49 genes and with a potentially functional KIR gene may represent an interesting model for evolutionary biology of NKR genes. PMID:23724088

Futas, Jan; Horin, Petr

2013-01-01

74

Behavioural anomalies in mice evoked by ``Tokyo'' disruption of the Vitamin D receptor gene  

E-print Network

Behavioural anomalies in mice evoked by ``Tokyo'' disruption of the Vitamin D receptor gene Allan V functional VDR (``Tokyo'' VDR mutant mice) display several behavioural anomalies, including high anxiety in the regulationof motor activity andbehaviour(Prufer et al., 1999; Langub et al., 2001; Walbert et al., 2001; Eyles

Kalueff, Allan V.

75

Structure of the Human Interleukin2 Receptor Gene  

Microsoft Academic Search

The gene encoding the human interleukin-2 (IL-2) receptor consists of 8 exons spanning more than 25 kilobases on chromosome 10. Exons 2 and 4 were derived from a gene duplication event and unexpectedly also are homologous to the recognition domain of human complement factor B. Alternative messenger RNA (mRNA) splicing may delete exon 4 sequences, resulting in a mRNA that

Warren J. Leonard; Joel M. Depper; Minoru Kanehisa; Martin Kronke; Nancy J. Peffer; Penny B. Svetlik; Margery Sullivan; Warner C. Greene

1985-01-01

76

Regulation of dihydropyridine receptor and ryanodine receptor gene expression in regenerating skeletal muscle  

Microsoft Academic Search

One of the the major properties of mature skeletal muscle is its ability to regenerate after injury. The purpose of the present\\u000a study was to determine whether the expression of genes encoding the dihydropyridine receptor calcium channel (DHPR) and the\\u000a ryanodine receptor (RyR), which play a critical role in excitation–contraction coupling, is regulated by skeletal muscle regeneration.\\u000a The process of

Yann Péréon; Javier Navarro; Vincenzo Sorrentino; Jean-Pierre Louboutin; Jacques Noireaud; P. Palade

1996-01-01

77

Characterisation of the legume SERK-NIK gene superfamily including splice variants: Implications for development and defence  

PubMed Central

Background SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) genes are part of the regulation of diverse signalling events in plants. Current evidence shows SERK proteins function both in developmental and defence signalling pathways, which occur in response to both peptide and steroid ligands. SERKs are generally present as small gene families in plants, with five SERK genes in Arabidopsis. Knowledge gained primarily through work on Arabidopsis SERKs indicates that these proteins probably interact with a wide range of other receptor kinases and form a fundamental part of many essential signalling pathways. The SERK1 gene of the model legume, Medicago truncatula functions in somatic and zygotic embryogenesis, and during many phases of plant development, including nodule and lateral root formation. However, other SERK genes in M. truncatula and other legumes are largely unidentified and their functions unknown. Results To aid the understanding of signalling pathways in M. truncatula, we have identified and annotated the SERK genes in this species. Using degenerate PCR and database mining, eight more SERK-like genes have been identified and these have been shown to be expressed. The amplification and sequencing of several different PCR products from one of these genes is consistent with the presence of splice variants. Four of the eight additional genes identified are upregulated in cultured leaf tissue grown on embryogenic medium. The sequence information obtained from M. truncatula was used to identify SERK family genes in the recently sequenced soybean (Glycine max) genome. Conclusions A total of nine SERK or SERK-like genes have been identified in M. truncatula and potentially 17 in soybean. Five M. truncatula SERK genes arose from duplication events not evident in soybean and Lotus. The presence of splice variants has not been previously reported in a SERK gene. Upregulation of four newly identified SERK genes (in addition to the previously described MtSERK1) in embryogenic tissue cultures suggests these genes also play a role in the process of somatic embryogenesis. The phylogenetic relationship of members of the SERK gene family to closely related genes, and to development and defence function is discussed. PMID:21385462

2011-01-01

78

Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism  

SciTech Connect

The allelic association of the human D2 dopamine receptor gene with the binding characteristics of the D2 dopamine receptor was determined in 66 brains of alcoholic and non-alcoholic subjects. In a blinded experiment, DNA from the cerebral cortex was treated with the restriction endonuclease Taql and probed with a 1.5-kilobase (kb) digest of a clone (lambda hD2G1) of the human D2 dopamine receptor gene. The binding characteristics (Kd (binding affinity) and Bmax (number of binding sites)) of the D2 dopamine receptor were determined in the caudate nuclei of these brains using tritiated spiperone as the ligand. The adjusted Kd was significantly lower in alcoholic than in nonalcoholic subjects. In subjects with the A1 allele, in whom a high association with alcoholism was found, the Bmax was significantly reduced compared with the Bmax of subjects with the A2 allele. Moreover, a progressively reduced Bmax was found in subjects with A2/A2, A1/A2, and A1/A1 alleles, with subjects with A2/A2 having the highest mean values, and subjects with A1/A1, the lowest. The polymorphic pattern of the D2 dopamine receptor gene and its differential expression of receptors suggests the involvement of the dopaminergic system in conferring susceptibility to at least one subtype of severe alcoholism.

Noble, E.P.; Blum, K.; Ritchie, T.; Montgomery, A.; Sheridan, P.J. (Neuropsychiatric Institute, UCLA (USA))

1991-07-01

79

Chemosensory receptor genes in the Oriental tobacco budworm Helicoverpa assulta.  

PubMed

The Oriental tobacco budworm (Helicoverpa assulta) is a specialist herbivore moth and its larvae feed on Solanaceous plants. (Z)-9-hexadecenal (Z9-16: Ald) is the major sex pheromone component in H.?assulta but the specific pheromone receptor (PR) against Z9-16: Ald has not yet been identified. In the present study, we integrated transcriptomic, bioinformatic and functional characterization approaches to investigate the chemosensory receptor genes of H.?assulta. We identified seven potential PRs with 44 olfactory receptors, 18 gustatory receptors and 24 ionotropic receptors, which were further studied by in silico gene expression profile, phylogenetic analysis, reverse transcription PCR and calcium imaging assays. The candidate PR, HassOR13, showed a strong response to the minor sex pheromone component, (Z)-11-hexadecenal, but not the major component, Z9-16: Ald, in calcium imaging assays. This study provides the molecular basis for comparative studies of chemosensory receptors between H.?assulta and other Helicoverpa species and will advance our understanding of the evolution and function of Lepidoptera insect chemosensation. PMID:25430896

Xu, W; Papanicolaou, A; Liu, N-Y; Dong, S-L; Anderson, A

2015-04-01

80

Association between Vitamin D Receptor Gene Polymorphism and Nephrolithiasis  

Microsoft Academic Search

Aims: To study the distribution of vitamin D receptor (VDR) gene alleles in hypercalciuric and nonhypercalciuric nephrolithiasis patients, hypothesizing that distinct biochemical parameters would be associated with different VDR genotypes. Methods: 12 hypercalciuric, 15 normocalciuric nephrolithiasis patients, and 150 healthy subjects were recruited. The individual genetic pattern for VDR was evaluated by DNA extraction followed by polymerase chain reaction amplification

Marco Ruggiero; Stefania Pacini; Marcello Amato; Stefano Aterini; Vincenzo Chiarugi

1999-01-01

81

EGF receptor gene mutations are common in lung cancers from  

Microsoft Academic Search

Somatic mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene are reportedly associated with sensitivity of lung cancers to gefitinib (Iressa), kinase inhibitor. In-frame deletions occur in exon 19, whereas point mutations occur frequently in codon 858 (exon 21). We found from sequencing the EGFR TK domain that 7 of 10 gefitinib-sensitive tumors had

William Pao; Vincent Miller; Maureen Zakowski; Jennifer Doherty; Katerina Politi; Inderpal Sarkaria; Bhuvanesh Singh; Robert Heelan; Valerie Rusch; Lucinda Fulton; Elaine Mardis; Doris Kupfer; Richard Wilson; Mark Kris; Harold Varmus

2004-01-01

82

The Glucocorticoid Receptor Gene and Its Association to Metabolic Syndrome  

Microsoft Academic Search

In recent decades, there has been an increasing interest in the role of endogenous glucocorticoids such as cortisol in the pathogenesis of metabolic syndrome. Studies in humans have suggested a positive association between obesity, hypertension, and insulin resistance, with alleles at the glucocorticoid receptor (GR) gene. For instance, the BclI polymorphism within the intron upstream of GR exon 2 has

Roland Rosmond

2002-01-01

83

Linkage analysis of schizophrenia with five dopamine receptor genes in nine pedigrees  

SciTech Connect

Alterations in dopamine neurotransmission have been strongly implicated in the pathogenesis of schizophrenia for nearly 2 decades. Recently, the genes for five dopamine receptors have been cloned and characterized, and genetic and physical map information has become available. Using these five loci as candidate genes, the authors have tested for genetic linkage to schizophrenia in nine multigenerational families which include multiple affected individuals. In addition to testing conservative disease models, the have used a neurophysiological indicator variable, the P50 auditory evoked response. Deficits in gating of the P50 response have been shown to segregate with schizophrenia in this sample and may identify carriers of gene(s) predisposing for schizophrenia. Linkage results were consistently negative, indicating that a defect at any of the actual receptor sites is unlikely to be a major contributor to schizophrenia in the nine families studied. 47 refs., 1 fig., 4 tabs.

Coon, H.; Byerley, W.; Holik, J.; Hoff, M.; Myles-Worsley, M.; Plaetke, R. (Univ. of Utah, Salt Lake City (United States)); Lannfelt, L. (Karolinska Inst., Stockholm (Sweden)); Sokoloff, P.; Schwartz, J.C. (Unite de Neurobiologie et de Pharmacologie de l'INSERM, Paris (France)); Waldo, M.; Freedman, R. (Univ. of Colorado, Denver (United States))

1993-02-01

84

Common Promoter Elements in Odorant and Vomeronasal Receptor Genes  

PubMed Central

In mammals, odorants and pheromones are detected by hundreds of odorant receptors (ORs) and vomeronasal receptors (V1Rs and V2Rs) expressed by sensory neurons that are respectively located in the main olfactory epithelium and in the vomeronasal organ. Even though these two olfactory systems are functionally and anatomically separate, their sensory neurons show a common mechanism of receptor gene regulation: each neuron expresses a single receptor gene from a single allele. The mechanisms underlying OR and VR gene expression remain unclear. Here we investigated if OR and V1R genes share common sequences in their promoter regions. We conducted a comparative analysis of promoter regions of 39 mouse V1R genes and found motifs that are common to a large number of promoters. We then searched mouse OR promoter regions for motifs that resemble the ones found in the V1R promoters. We identified motifs that are present in both the V1R and OR promoter regions. Some of these motifs correspond to the known O/E like binding sites while others resemble binding sites for transcriptional repressors. We show that one of these motifs specifically interacts with proteins extracted from both nuclei from olfactory and vomeronasal neurons. Our study is the first to identify motifs that resemble binding sites for repressors in the promoters of OR and V1R genes. Analysis of these motifs and of the proteins that bind to these motifs should reveal important aspects of the mechanisms of OR/V1R gene regulation. PMID:22216168

Michaloski, Jussara S.; Galante, Pedro A. F.; Nagai, Maíra H.; Armelin-Correa, Lucia; Chien, Ming-Shan; Matsunami, Hiroaki; Malnic, Bettina

2011-01-01

85

Identification of chemosensory receptor genes in Manduca sexta and knockdown by RNA interference  

PubMed Central

Background Insects detect environmental chemicals via a large and rapidly evolving family of chemosensory receptor proteins. Although our understanding of the molecular genetic basis for Drosophila chemoreception has increased enormously in the last decade, similar understanding in other insects remains limited. The tobacco hornworm, Manduca sexta, has long been an important model for insect chemosensation, particularly from ecological, behavioral, and physiological standpoints. It is also a major agricultural pest on solanaceous crops. However, little sequence information and lack of genetic tools has prevented molecular genetic analysis in this species. The ability to connect molecular genetic mechanisms, including potential lineage-specific changes in chemosensory genes, to ecologically relevant behaviors and specializations in M. sexta would be greatly beneficial. Results Here, we sequenced transcriptomes from adult and larval chemosensory tissues and identified chemosensory genes based on sequence homology. We also used dsRNA feeding as a method to induce RNA interference in larval chemosensory tissues. Conclusions We report identification of new chemosensory receptor genes including 17 novel odorant receptors and one novel gustatory receptor. Further, we demonstrate that systemic RNA interference can be used in larval olfactory neurons to reduce expression of chemosensory receptor transcripts. Together, our results further the development of M. sexta as a model for functional analysis of insect chemosensation. PMID:22646846

2012-01-01

86

Gene expression profiles of estrogen receptor positive and estrogen receptor negative breast cancers are detectable in histologically normal breast epithelium  

PubMed Central

Purpose Previously, we found that gene expression in histologically normal breast epithelium (NlEpi) from women at high breast cancer risk can resemble gene expression in NlEpi from cancer-containing breasts. Therefore, we hypothesized that gene expression characteristic of a cancer subtype might be seen in NlEpi of breasts containing that subtype. Experimental Design We examined gene expression in 46 cases of microdissected NlEpi from untreated women undergoing breast cancer surgery. From 30 age-matched cases (15 estrogen receptor (ER)+, 15 ER-) we used Affymetryix U133A arrays. From 16 independent cases (9 ER+, 7 ER-), we validated selected genes using qPCR. We then compared gene expression between NlEpi and invasive breast cancer using 4 publicly available datasets. Results We identified 198 genes that are differentially expressed between NlEpi from breasts with ER+ (NlEpiER+) compared to ER- cancers (NlEpiER-). These include genes characteristic of ER+ and ER- cancers (e.g., ESR1, GATA3, and CX3CL1, FABP7). QPCR validated the microarray results in both the 30 original cases and the 16 independent cases. Gene expression in NlEpiER+ and NlEpiER- resembled gene expression in ER+ and ER- cancers, respectively: 25-53% of the genes or probes examined in 4 external datasets overlapped between NlEpi and the corresponding cancer subtype. Conclusions Gene expression differs in NlEpi of breasts containing ER+ compared to ER- breast cancers. These differences echo differences in ER+ and ER- invasive cancers. NlEpi gene expression may help elucidate subtype-specific risk signatures, identify early genomic events in cancer development and locate targets for prevention and therapy. PMID:21059815

Graham, Kelly; Ge, Xijin; de las Morenas, Antonio; Tripathi, Anusri; Rosenberg, Carol L.

2010-01-01

87

Molecular evolution of the odorant and gustatory receptor genes in lepidopteran insects: implications for their adaptation and speciation.  

PubMed

Lepidoptera (comprised of butterflies and moths) is one of the largest groups of insects, including more than 160,000 described species. Chemoreception plays important roles in the adaptation of these species to a wide range of niches, e.g., plant hosts, egg-laying sites, and mates. This study investigated the molecular evolution of the lepidopteran odorant (Or) and gustatory receptor (Gr) genes using recently identified genes from Bombyx mori, Danaus plexippus, Heliconius melpomene, Plutella xylostella, Heliothis virescens, Manduca sexta, Cydia pomonella, and Spodoptera littoralis. A limited number of cases of large lineage-specific gene expansion are observed (except in the P. xylostella lineage), possibly due to selection against tandem gene duplication. There has been strong purifying selection during the evolution of both lepidopteran odorant and gustatory genes, as shown by the low ? values estimated through CodeML analysis, ranging from 0.0093 to 0.3926. However, purifying selection has been relaxed on some amino acid sites in these receptors, leading to sequence divergence, which is a precursor of positive selection on these sequences. Signatures of positive selection were detected only in a few loci from the lineage-specific analysis. Estimation of gene gains and losses suggests that the common ancestor of the Lepidoptera had fewer Or genes compared to extant species and an even more reduced number of Gr genes, particularly within the bitter receptor clade. Multiple gene gains and a few gene losses occurred during the evolution of Lepidoptera. Gene family expansion may be associated with the adaptation of lepidopteran species to plant hosts, especially after angiosperm radiation. Phylogenetic analysis of the moth sex pheromone receptor genes suggested that chromosomal translocations have occurred several times. New sex pheromone receptors have arisen through tandem gene duplication. Positive selection was detected at some amino acid sites predicted to be in the extracellular and transmembrane regions of the newly duplicated genes, which might be associated with the evolution of the new pheromone receptors. PMID:25038840

Engsontia, Patamarerk; Sangket, Unitsa; Chotigeat, Wilaiwan; Satasook, Chutamas

2014-08-01

88

Chromosomal localization of the human V3 pituitary vasopressin receptor gene (AVPR3) to 1q32  

SciTech Connect

Vasopressin exerts its physiological effects on liver metabolism, fluid osmolarity, and corticotrophic response to stress through a set of at least three receptors, V1a, V2, and V3 (also called V1b), respectively. These receptors constitute a distinct group of the superfamily of G-protein-coupled cell surface receptors. When bound to vasopressin, they couple to G proteins activating phospholipase C for the V1a and V3 types and adenylate cyclase for the V2. The vasopressin receptor subfamily also includes the receptor for oxytocin, a structurally related hormone that signals through the activation of phospholipase C. The chromosomal position of the V2 receptor gene has been assigned to Xq28-qter by PCR-based screening of somatic cell hybrids, whereas the oxytocin receptor gene has been mapped to chromosome 3q26.2 by fluorescence in situ hybridization (FISH). The chromosomal location of the V1a gene is currently unknown. We recently cloned the cDNA and the gene coding for the human pituitary-specific V3 receptor (HGMW-approved symbol AVPR3). We report here the chromosomal localization of this gene by two distinct in situ hybridization techniques using radioactive and fluorescent probes. 11 refs., 1 fig.

Rousseau-Merck, M.F.; Derre, J.; Berger, R. [INSERM, Paris (France)] [and others

1995-11-20

89

CRDB: Database of Chemosensory Receptor Gene Families in Vertebrate  

PubMed Central

Chemosensory receptors (CR) are crucial for animals to sense the environmental changes and survive on earth. The emergence of whole-genome sequences provides us an opportunity to identify the entire CR gene repertoires. To completely gain more insight into the evolution of CR genes in vertebrates, we identified the nearly all CR genes in 25 vertebrates using homology-based approaches. Among these CR gene repertoires, nearly half of them were identified for the first time in those previously uncharacterized species, such as the guinea pig, giant panda and elephant, etc. Consistent with previous findings, we found that the numbers of CR genes vary extensively among different species, suggesting an extreme form of ‘birth-and-death’ evolution. For the purpose of facilitating CR gene analysis, we constructed a database with the goals to provide a resource for CR genes annotation and a web tool for exploring their evolutionary patterns. Besides a search engine for the gene extraction from a specific chromosome region, an easy-to-use phylogenetic analysis tool was also provided to facilitate online phylogeny study of CR genes. Our work can provide a rigorous platform for further study on the evolution of CR genes in vertebrates. PMID:22393364

Wu, Xiaoli; Zhong, Yang

2012-01-01

90

CRDB: database of chemosensory receptor gene families in vertebrate.  

PubMed

Chemosensory receptors (CR) are crucial for animals to sense the environmental changes and survive on earth. The emergence of whole-genome sequences provides us an opportunity to identify the entire CR gene repertoires. To completely gain more insight into the evolution of CR genes in vertebrates, we identified the nearly all CR genes in 25 vertebrates using homology-based approaches. Among these CR gene repertoires, nearly half of them were identified for the first time in those previously uncharacterized species, such as the guinea pig, giant panda and elephant, etc. Consistent with previous findings, we found that the numbers of CR genes vary extensively among different species, suggesting an extreme form of 'birth-and-death' evolution. For the purpose of facilitating CR gene analysis, we constructed a database with the goals to provide a resource for CR genes annotation and a web tool for exploring their evolutionary patterns. Besides a search engine for the gene extraction from a specific chromosome region, an easy-to-use phylogenetic analysis tool was also provided to facilitate online phylogeny study of CR genes. Our work can provide a rigorous platform for further study on the evolution of CR genes in vertebrates. PMID:22393364

Dong, Dong; Jin, Ke; Wu, Xiaoli; Zhong, Yang

2012-01-01

91

The orphan G-protein-coupled receptor-encoding gene V28 is closely related to genes for chemokine receptors and is expressed in lymphoid and neural tissues  

Microsoft Academic Search

A polymerase chain reaction (PCR) strategy with degenerate primers was used to identify novel G-protein-coupled receptor-encoding genes from human genomic DNA. One of the isolated clones, termed V28, showed high sequence similarity to the genes encoding human chemokine receptors for monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein l?(MIP-1?)\\/RANTES, and to the rat orphan receptor-encoding gene RBS11. When RNA

Carol J. Raport; Vicki L. Schweickart; Roger L. Eddy; Thomas B. Shows; Patrick W. Gray

1995-01-01

92

A candidate taste receptor gene near a sweet taste locus.  

PubMed

The mechanisms underlying sweet taste in mammals have been elusive. Although numerous studies have implicated G proteins in sweet taste detection, the expected G protein-coupled receptors have not been found. Here we describe a candidate taste receptor gene, T1r3, that is located at or near the mouse Sac locus, a genetic locus that controls the detection of certain sweet tastants. T1R3 differs in amino acid sequence in mouse strains with different Sac phenotypes ('tasters' versus 'nontasters'). In addition, a perfect correlation exists between two different T1r3 alleles and Sac phenotypes in recombinant inbred mouse strains. The T1r3 gene is expressed in a subset of taste cells in circumvallate, foliate and fungiform taste papillae. In circumvallate and foliate papillae, most T1r3-expressing cells also express a gene encoding a related receptor, T1R2, raising the possibility that these cells recognize more than one ligand, or that the two receptors function as heterodimers. PMID:11319557

Montmayeur, J P; Liberles, S D; Matsunami, H; Buck, L B

2001-05-01

93

Symptoms of Attention-Deficit/Hyperactivity Disorder in Down Syndrome: Effects of the Dopamine Receptor D4 Gene  

ERIC Educational Resources Information Center

This study examined individual differences in ADHD symptoms and executive function (EF) in children with Down syndrome (DS) in relation to the dopamine receptor D4 (DRD4) gene, a gene often linked to ADHD in people without DS. Participants included 68 individuals with DS (7-21 years), assessed through laboratory tasks, caregiver reports, and…

Mason, Gina Marie; Spanó, Goffredina; Edgin, Jamie

2015-01-01

94

Insect storage proteins: gene families and receptors.  

PubMed

The accumulation and utilization of storage proteins are prominent events linked to the metamorphosis of holometabolous insects. Storage proteins are synthesized in fat body, secreted into the larval hemolymph and taken up by fat body shortly before pupation. Within the pupal fat body, these proteins are initially stored in protein granules, and later proteolytically broken down to supply amino acid resources necessary for the completion of adult development. Most, but not all storage proteins belong to a superfamily of hexameric larval serum proteins that are evolutionarily related to hemocyanin. This article reviews the classification of these proteins, based on their amino acid sequences, and the current knowledge of the receptors that mediate their selective uptake into pupal fat body. PMID:9014325

Haunerland, N H

1996-01-01

95

Modulation of oestrogen action by receptor gene inhibition.  

PubMed

Selective oestrogen receptor downregulators (SERDs) are a class of highly effective steroidal antitumour agents that reduce cellular levels of the oestrogen receptor (ER). In this study, we compared the efficacy by which three novel molecular approaches: (1) antisense oligonucleotides; (2) antisense RNA; and (3) dominant negative mutants are able to act as SERDs. Using transient and, where appropriate, stable gene transfection experiments we found that constitutive overexpression of ER antisense RNA and a hormone-binding domain compromised dominant-negative ER mutant (DNER-1), were most effective at downregulating ER expression and/or activity in vitro. PMID:11056309

Madden, T A; Barrow, D; McClelland, R A; Gee, J M; Nicholson, R I

2000-09-01

96

Parallel evolution of domesticated Caenorhabditis species targets pheromone receptor genes  

PubMed Central

Evolution can follow predictable genetic trajectories1, indicating that discrete environmental shifts can select for reproducible genetic changes2-4. Conspecific individuals are an important feature of an animal's environment, and a potential source of selective pressures. We show here that adaptation of two Caenorhabditis species to growth at high density, a feature common to domestic environments, occurs by reproducible genetic changes to pheromone receptor genes. Chemical communication through pheromones that accumulate during high-density growth causes young nematode larvae to enter the long-lived but non-reproductive dauer stage. Two strains of Caenorhabditis elegans grown at high density have independently acquired multigenic resistance to pheromone-induced dauer formation. In each strain, resistance to the pheromone ascaroside C3 results from a deletion that disrupts the adjacent chemoreceptor genes serpentine receptor class g (srg)-36 and -37. Through misexpression experiments, we show that these genes encode redundant G protein-coupled receptors for ascaroside C3. Multigenic resistance to dauer formation has also arisen in high-density cultures of a different nematode species, Caenorhabditis briggsae, resulting in part from deletion of an srg gene paralogous to srg-36 and srg-37. These results demonstrate rapid remodeling of the chemoreceptor repertoire as an adaptation to specific environments, and indicate that parallel changes to a common genetic substrate can affect life history traits across species. PMID:21849976

McGrath, Patrick T.; Xu, Yifan; Ailion, Michael; Garrison, Jennifer L.; Butcher, Rebecca A.; Bargmann, Cornelia I.

2011-01-01

97

Regulation of Proteome Maintenance Gene Expression by Activators of Peroxisome Proliferator-Activated Receptor ?  

PubMed Central

The nuclear receptor peroxisome proliferator-activated receptor ? (PPAR?) is activated by a large number of xenobiotic and hypolipidemic compounds called peroxisome proliferator chemicals (PPCs). One agonist of PPAR? (WY-14,643) regulates responses in the mouse liver to chemical stress in part by altering expression of genes involved in proteome maintenance (PM) including protein chaperones in the heat shock protein (Hsp) family and proteasomal genes (Psm) involved in proteolysis. We hypothesized that other PPAR? activators including diverse hypolipidemic and xenobiotic compounds also regulate PM genes in the rat and mouse liver. We examined the expression of PM genes in rat and mouse liver after exposure to 7 different PPCs (WY-14,643, clofibrate, fenofibrate, valproic acid, di-(2-ethylhexyl) phthalate, perfluorooctanoic acid, and perfluorooctane sulfonate) using Affymetrix microarrays. In rats and mice, 174 or 380?PM genes, respectively, were regulated by at least one PPC. The transcriptional changes were, for the most part, dependent on PPAR?, as most changes were not observed in similarly treated PPAR?-null mice and the changes were not consistently observed in rats treated with activators of the nuclear receptors CAR or PXR. In rats and mice, PM gene expression exhibited differences compared to typical direct targets of PPAR? (e.g., Cyp4a family members). PM gene expression was usually delayed and in some cases, it was transient. Dose-response characterization of protein expression showed that Hsp86 and Hsp110 proteins were induced only at higher doses. These studies demonstrate that PPAR?, activated by diverse PPC, regulates the expression of a large number of genes involved in protein folding and degradation and support an expanded role for PPAR? in the regulation of genes that protect the proteome. PMID:21318169

Ren, Hongzu; Vallanat, Beena; Brown-Borg, Holly M.; Currie, Richard; Corton, J. Christopher

2010-01-01

98

Regulation of Proteome Maintenance Gene Expression by Activators of Peroxisome Proliferator-Activated Receptor ?.  

PubMed

The nuclear receptor peroxisome proliferator-activated receptor ? (PPAR?) is activated by a large number of xenobiotic and hypolipidemic compounds called peroxisome proliferator chemicals (PPCs). One agonist of PPAR? (WY-14,643) regulates responses in the mouse liver to chemical stress in part by altering expression of genes involved in proteome maintenance (PM) including protein chaperones in the heat shock protein (Hsp) family and proteasomal genes (Psm) involved in proteolysis. We hypothesized that other PPAR? activators including diverse hypolipidemic and xenobiotic compounds also regulate PM genes in the rat and mouse liver. We examined the expression of PM genes in rat and mouse liver after exposure to 7 different PPCs (WY-14,643, clofibrate, fenofibrate, valproic acid, di-(2-ethylhexyl) phthalate, perfluorooctanoic acid, and perfluorooctane sulfonate) using Affymetrix microarrays. In rats and mice, 174 or 380?PM genes, respectively, were regulated by at least one PPC. The transcriptional changes were, for the most part, dependent on PPAR?, as most changes were not observed in similarly treated PPAR?-null mice and the changes were not consistently observed in rats treated with activators of the nuclear receptors CAR or PXR. In rats and mice, PM gene expression exhibited differences compared to typical direct targets of PPAR? (e.g., Cyp4a family members). PM gene expression was usually delayed and in some cases, it was transient. Dose-response characterization of protein expression showed that Hsp86 and Hsp110 proteins were induced only at higher doses. These studies demonstrate that PPAR?, activated by diverse PPC, regulates the expression of a large number of genes involved in protein folding and degradation and support an expanded role for PPAR? in the regulation of genes that protect the proteome. PMID:21318169

Ren, Hongzu; Vallanat, Beena; Brown-Borg, Holly M; Currie, Richard; Corton, J Christopher

2010-01-01

99

Relationship between the level of hippocampal leptin receptor gene expression and learning performance in diabetic rats.  

PubMed

Diabetes mellitus may be associated with impaired cognitive function. Decreased peripheral glucose regulation was associated with decreased general cognitive performance, memory impairments, and atrophy of the hippocampus, a brain area that is key for learning and memory. Leptin that is a peptide hormone, acts in the hippocampus where it facilitates the induction of long-term potentiation and enhances NMDA receptor mediated transmission. The aim of the present study is to investigate possible relationship between the hippocampal leptin receptor gene expression and learning performance in streptozotocin (STZ) induced diabetic rats. In this study was conducted on a total of 40 Winstar albino female rats, including a control group consisting of 20 rats and experimental group comprising of 20 rats in which diabetes was induced by means of STZ administration. Leptin receptor gene expression was detected in hippocampal samples by using real time-PCR. According to the evaluation, the learning performance of rats with induced diabetes was found to be same throughout the first 3 days after STZ in comparison to the control group rats. End of the 45 days the learning performance of the control group was found to be better than the diabetic group (p<0.05). Hipocampal leptin receptor expression was found lower in diabetic group than the control group (p<0.05). The results provide evidence that leptin receptor gene may related to learning performance in diabetic rats. Further, detailed studies are needed to address the exact role of leptin and related molecules in learning performance. PMID:25380550

Demirel, C; Balc?, S O; Korkmaz, H; Akarsu, E

2014-11-01

100

Unraveling gene-gene interactions regulated by ligands of the aryl hydrocarbon receptor.  

PubMed Central

The co-expression of genes coupled to additive probabilistic relationships was used to identify gene sets predictive of the complex biological interactions regulated by ligands of the aryl hydrocarbon receptor ((Italic)Ahr(/Italic)). To maximize the number of possible gene-gene combinations, data sets from murine embryonic kidney, fetal heart, and vascular smooth muscle cells challenged (Italic)in vitro(/Italic) with ligands of the (Italic)Ahr(/Italic) were used to create predictor/training data sets. Biologically relevant gene predictor sets were calculated for (Italic)Ahr(/Italic), cytochrome P450 1B1, insulin-like growth factor-binding protein-5, lysyl oxidase, and osteopontin. Transcript levels were categorized into ternary expressions and target genes selected from the data set and tested for all possible combinations using three gene sets as predictors of transitional level. The goodness of prediction for each set was quantified using a multivariate nonlinear coefficient of determination. Evidence is presented that predictor gene combinations can be effectively used to resolve gene-gene interactions regulated by (Italic)Ahr(/Italic) ligands. (Italic)Key words:(/Italic) aryl hydrocarbon receptor, bioinformatics, gene networks, genomics. (Italic)Environ Health Perspect (/Italic)112:403-412 (2004). [Online 14 January 2004] PMID:15033587

Johnson, Charles D; Balagurunathan, Yoganand; Tadesse, Mahlet G; Falahatpisheh, M Hadi; Brun, Marcel; Walker, Mary K; Dougherty, Edward R; Ramos, Kenneth S

2004-01-01

101

Gene number determination and genetic polymorphism of the gamma delta T cell co-receptor WC1 genes  

Technology Transfer Automated Retrieval System (TEKTRAN)

Background WC1 co-receptors belong to the scavenger receptor cysteine-rich superfamily and are encoded by a multi-gene family. Expression of particular WC1 genes defines functional subpopulations of WC1+ '' T cells. Our previous study identified partial sequences for 13 different WC1 genes by annota...

102

Cutaneous Lesions in the Rat Following Administration of an Irreversible Inhibitor of erbB Receptors, Including the Epidermal Growth Factor Receptor  

Microsoft Academic Search

CI-1033 (canertinib) is an irreversible inhibitor of the erbB family of transmembrane tyrosine kinase receptors, including the epidermal growth factor (EGF) receptor. Various inhibitors of the EGF receptor, including CI-1033, have resulted in cutaneous toxicity in humans as a common adverse event. In a chronic toxicity study in rats, CI-1033 produced cutaneous lesions with morphologic characteristics similar to that reported

ALAN P. B ROWN; R OBERT W. D UNSTAN; L. COURTNEY; K AY A. CRISWELL; MICHAEL J. GRAZIANO

2010-01-01

103

A transcriptionally active human type II gonadotropin-releasing hormone receptor gene homolog overlaps two genes in the antisense orientation on chromosome 1q.12.  

PubMed

GnRH-II peptide hormone exhibits complete sequence conservation across vertebrate species, including man. Type-II GnRH receptor genes have been characterized recently in nonhuman primates, but the human receptor gene homolog contains a frameshift, a premature stop codon (UGA), and a 3' overlap of the RBM8A gene on chromosome 1q.12. A retrotransposed pseudogene, RBM8B, retains partial receptor sequence. In this study, bioinformatics show that the human receptor gene promoter overlaps the peroxisomal protein 11-beta gene promoter and the premature UGA is positionally conserved in chimpanzee. A CGA [arginine (Arg)] occurs in porcine DNA, but UGA is shifted one codon to the 5' direction in bovine DNA, suggesting independent evolution of premature stop codons. In contrast to marmoset tissue RNA, exon- and strand-specific probes are required to distinguish differently spliced human receptor gene transcripts in cell lines (HP75, IMR-32). RBM8B is not transcribed. Sequencing of cDNAs for spliced receptor mRNAs showed no evidence for alteration of the premature UGA by RNA editing, but alternative splicing circumvents the frameshift to encode a two-membrane-domain protein before this UGA. A stem-loop motif resembling a selenocysteine insertion sequence and a potential alternative translation initiation site might enable expression of further proteins involved in interactions within the GnRH system. PMID:12538601

Morgan, Kevin; Conklin, Darrell; Pawson, Adam J; Sellar, Robin; Ott, Thomas R; Millar, Robert P

2003-02-01

104

Identification of novel androgen receptor target genes in prostate cancer  

PubMed Central

Background The androgen receptor (AR) plays critical roles in both androgen-dependent and castrate-resistant prostate cancer (PCa). However, little is known about AR target genes that mediate the receptor's roles in disease progression. Results Using Chromatin Immunoprecipitation (ChIP) Display, we discovered 19 novel loci occupied by the AR in castrate resistant C4-2B PCa cells. Only four of the 19 AR-occupied regions were within 10-kb 5'-flanking regulatory sequences. Three were located up to 4-kb 3' of the nearest gene, eight were intragenic and four were in gene deserts. Whereas the AR occupied the same loci in C4-2B (castrate resistant) and LNCaP (androgen-dependent) PCa cells, differences between the two cell lines were observed in the response of nearby genes to androgens. Among the genes strongly stimulated by DHT in C4-2B cells – D-dopachrome tautomerase (DDT), Protein kinase C delta (PRKCD), Glutathione S- transferase theta 2 (GSTT2), Transient receptor potential cation channel subfamily V member 3 (TRPV3), and Pyrroline-5-carboxylate reductase 1 (PYCR1) – most were less strongly or hardly stimulated in LNCaP cells. Another AR target gene, ornithine aminotransferase (OAT), was AR-stimulated in a ligand-independent manner, since it was repressed by AR siRNA knockdown, but not stimulated by DHT. We also present evidence for in vivo AR-mediated regulation of several genes identified by ChIP Display. For example, PRKCD and PYCR1, which may contribute to PCa cell growth and survival, are expressed in PCa biopsies from primary tumors before and after ablation and in metastatic lesions in a manner consistent with AR-mediated stimulation. Conclusion AR genomic occupancy is similar between LNCaP and C4-2B cells and is not biased towards 5' gene flanking sequences. The AR transcriptionally regulates less than half the genes nearby AR-occupied regions, usually but not always, in a ligand-dependent manner. Most are stimulated and a few are repressed. In general, response is stronger in C4-2B compared to LNCaP cells. Some of the genes near AR-occupied regions appear to be regulated by the AR in vivo as evidenced by their expression levels in prostate cancer tumors of various stages. Several AR target genes discovered in the present study, for example PRKCD and PYCR1, may open avenues in PCa research and aid the development of new approaches for disease management. PMID:17553165

Jariwala, Unnati; Prescott, Jennifer; Jia, Li; Barski, Artem; Pregizer, Steve; Cogan, Jon P; Arasheben, Armin; Tilley, Wayne D; Scher, Howard I; Gerald, William L; Buchanan, Grant; Coetzee, Gerhard A; Frenkel, Baruch

2007-01-01

105

Sheep exhibit novel variations in the organization of the mammalian type II gonadotropin-releasing hormone receptor gene.  

PubMed

Species-specific differences in genes encoding type II GnRH receptor indicate that a functional hepta-helical receptor is produced in monkeys but not in rodents, cows, chimpanzees, or humans. To further investigate the extent of evolutionary differences, we sequenced the type II GnRH receptor gene from wild-type Soay sheep. The gene was isolated by long-distance PCR using primers to PEX11beta and RBM8A genes known to flank type II GnRH receptor gene homologues. The gene spans 5.7-kb DNA and was sequenced after shot-gun subcloning. Its novel features include absence of a Pit-1 transcription factor binding site, a premature stop codon (TAG) in exon 1, an in-frame deletion of 51 bp (17 codons) in exon 2, and several nonconservative codon changes. Sheep breed variation in the gene was assessed using genomic DNA in PCR-restriction digest assays for the premature stop codon and in a PCR assay for the deletion. Both characteristics were present in all 15 breeds tested. Receptor gene expression was investigated using poly-A(+) RNA Northern analysis, RT-PCR, and in situ hybridization. An oligonucleotide probe to exon 1 revealed an alternative transcript in testis but not in pituitary gland. No transcripts in testis or pituitary were detectable using an exon 2-3 probe. All tissues examined including multiple brain areas and gonadotrope-enriched cell cultures were negative for type II GnRH receptor in RT-PCR. Testis and pituitary sections were negative with exon 1 riboprobes and exon 1 or 2-3 oligonucleotide probes in in situ hybridization. A hepta-helical type II GnRH receptor is therefore not expressed from this sheep gene. PMID:14749360

Gault, Paula M; Morgan, Kevin; Pawson, Adam J; Millar, Robert P; Lincoln, Gerald A

2004-05-01

106

Multiple Yeast Genes, Including Paf1 Complex Genes, Affect Telomere Length via Telomerase RNA Abundance? †  

PubMed Central

Twofold reductions in telomerase RNA levels cause telomere shortening in both humans and the yeast Saccharomyces cerevisiae. To test whether multiple genes that affect telomere length act by modulating telomerase RNA abundance, we used real-time reverse transcription-PCR to screen S. cerevisiae deletion strains reported to maintain shorter or longer telomeres to determine the levels of their telomerase RNA (TLC1) abundance. Of 290 strains screened, 5 had increased TLC1 levels; 4 of these maintained longer telomeres. Twenty strains had decreased TLC1 levels; 18 of these are known to maintain shorter telomeres. Four strains with decreased TLC1 RNA levels contained deletions of subunits of Paf1C (polymerase II-associated factor complex). While Paf1C had been implicated in the transcription of both polyadenylated and nonpolyadenylated RNAs, Paf1C had not been associated previously with the noncoding telomerase RNA. In Paf1C mutant strains, TLC1 overexpression partially rescues telomere length and cell growth defects, suggesting that telomerase RNA is a critical direct or indirect Paf1C target. Other factors newly identified as affecting TLC1 RNA levels include cyclin-dependent kinase, the mediator complex, protein phosphatase 2A, and ribosomal proteins L13B and S16A. This report establishes that a subset of telomere length genes act by modulating telomerase RNA abundance. PMID:18411302

Mozdy, Amy D.; Podell, Elaine R.; Cech, Thomas R.

2008-01-01

107

Dynamic evolution of bitter taste receptor genes in vertebrates  

PubMed Central

Background Sensing bitter tastes is crucial for many animals because it can prevent them from ingesting harmful foods. This process is mainly mediated by the bitter taste receptors (T2R), which are largely expressed in the taste buds. Previous studies have identified some T2R gene repertoires, and marked variation in repertoire size has been noted among species. However, the mechanisms underlying the evolution of vertebrate T2R genes remain poorly understood. Results To better understand the evolutionary pattern of these genes, we identified 16 T2R gene repertoires based on the high coverage genome sequences of vertebrates and studied the evolutionary changes in the number of T2R genes during birth-and-death evolution using the reconciled-tree method. We found that the number of T2R genes and the fraction of pseudogenes vary extensively among species. Based on the results of phylogenetic analysis, we showed that T2R gene families in teleost fishes are more diverse than those in tetrapods. In addition to the independent gene expansions in teleost fishes, frogs and mammals, lineage-specific gene duplications were also detected in lizards. Furthermore, extensive gains and losses of T2R genes were detected in each lineage during their evolution, resulting in widely differing T2R gene repertoires. Conclusion These results further support the hypotheses that T2R gene repertoires are closely related to the dietary habits of different species and that birth-and-death evolution is associated with adaptations to dietary changes. PMID:19144204

Dong, Dong; Jones, Gareth; Zhang, Shuyi

2009-01-01

108

Differential expression of olfactory genes in the southern house mosquito and insights into unique odorant receptor gene isoforms.  

PubMed

The southern house mosquito, Culex quinquefasciatus, has one of the most acute and eclectic olfactory systems of all mosquito species hitherto studied. Here, we used Illumina sequencing to identify olfactory genes expressed predominantly in antenna, mosquito's main olfactory organ. Less than 50% of the trimmed reads generated by high-quality libraries aligned to a transcript, but approximately 70% of them aligned to the genome. Differential expression analysis, which was validated by quantitative real-time PCR on a subset of genes, showed that approximately half of the 48 odorant-binding protein genes were enriched in antennae, with the other half being predominantly expressed in legs. Similar patterns were observed with chemosensory proteins, "plus-C" odorant-binding proteins, and sensory neuron membrane proteins. Transcripts for as many as 43 ionotropic receptors were enriched in female antennae, thus making the ionotropic receptor family the largest of antennae-rich olfactory genes, second only to odorant receptor (OR) genes. As many as 177 OR genes have been identified, including 36 unique transcripts. The unique OR genes differed from previously annotated ORs in internal sequences, splice variants, and extended N or C terminus. One of the previously unknown transcripts was validated by cloning and functional expression. When challenged with a large panel of physiologically relevant compounds, CquiOR95b responded in a dose-dependent manner to ethyl 2-phenylacteate, which was demonstrated to repel Culex mosquitoes, and secondarily to citronellal, a known insect repellent. This transcriptome study led to identification of key molecular components and a repellent for the southern house mosquito. PMID:24167245

Leal, Walter S; Choo, Young-Moo; Xu, Pingxi; da Silva, Cherre S B; Ueira-Vieira, Carlos

2013-11-12

109

Differential expression of olfactory genes in the southern house mosquito and insights into unique odorant receptor gene isoforms  

PubMed Central

The southern house mosquito, Culex quinquefasciatus, has one of the most acute and eclectic olfactory systems of all mosquito species hitherto studied. Here, we used Illumina sequencing to identify olfactory genes expressed predominantly in antenna, mosquito’s main olfactory organ. Less than 50% of the trimmed reads generated by high-quality libraries aligned to a transcript, but approximately 70% of them aligned to the genome. Differential expression analysis, which was validated by quantitative real-time PCR on a subset of genes, showed that approximately half of the 48 odorant-binding protein genes were enriched in antennae, with the other half being predominantly expressed in legs. Similar patterns were observed with chemosensory proteins, “plus-C” odorant-binding proteins, and sensory neuron membrane proteins. Transcripts for as many as 43 ionotropic receptors were enriched in female antennae, thus making the ionotropic receptor family the largest of antennae-rich olfactory genes, second only to odorant receptor (OR) genes. As many as 177 OR genes have been identified, including 36 unique transcripts. The unique OR genes differed from previously annotated ORs in internal sequences, splice variants, and extended N or C terminus. One of the previously unknown transcripts was validated by cloning and functional expression. When challenged with a large panel of physiologically relevant compounds, CquiOR95b responded in a dose-dependent manner to ethyl 2-phenylacteate, which was demonstrated to repel Culex mosquitoes, and secondarily to citronellal, a known insect repellent. This transcriptome study led to identification of key molecular components and a repellent for the southern house mosquito. PMID:24167245

Leal, Walter S.; Choo, Young-Moo; Xu, Pingxi; da Silva, Cherre S. B.; Ueira-Vieira, Carlos

2013-01-01

110

Association of Retinoic Acid Receptor Genes with Meningomyelocele  

PubMed Central

BACKGROUND Neural tube defects (NTDs) occur in as many as 0.5–2 per 1000 live births in the United ‘States. One of the most common and severe neural tube defects is meningomyelocele (MM) resulting from failed closure of the caudal end of the neural tube. MM has been induced by retinoic acid teratogenicity in rodent models. We hypothesized that genetic variants influencing retinoic acid (RA) induction via retinoic acid receptors (RARs) may be associated with risk for MM. METHODS We analyzed 47 single nucleotide polymorphisms (SNPs) that span across the three retinoic acid receptor genes using the SNPlex genotyping platform. Our cohort consisted of 610 MM families. RESULTS One variant in the RARA gene (rs12051734), three variants in the RARB gene (rs6799734, rs12630816, rs17016462), and a single variant in the RARG gene (rs3741434) were found to be statistically significant at p < 0.05. CONCLUSION RAR genes were associated with risk for MM. For all associated SNPs, the rare allele conferred a protective effect for MM susceptibility. PMID:21254357

Tran, Phong X.; Au, Kit Sing; Morrison, Alanna C.; Fletcher, Jack M.; Ostermaier, Kathryn K.; Tyerman, Gayle H.; Northrup, Hope

2011-01-01

111

Neuropeptide S Receptor 1: an Asthma Susceptibility Gene  

Microsoft Academic Search

The positional cloning of Neuropeptide S receptor (NPSR1) as an asthma susceptibility gene highlighted the notion that many\\u000a relevant disease pathways may have remained undiscovered until recently. Robust replications of the genetic effect of NPSR1\\u000a in asthma have paved a way for interaction studies. In a rapid pace, knowledge has been accumulated of the ligand and its\\u000a pharmacology as well

Juha Kere

112

Somatic and germline mutations of the TSH receptor gene in thyroid diseases  

SciTech Connect

Under physiological circumstances, thyrotropin (TSH) is the primary hormone that controls thyroid function and growth. TSH acts by binding to its receptor at the basolateral membrane of thyroid follicular cells. The TSH receptor is a member of the large family of G protein-coupled receptors, which share a similar structural pattern: seven transmembrane segments connected by three extra and three intracellular loops. Together with the receptors for other glycoprotein hormones LH/CG and FSH, the TSH receptor has a long aminoterminal domain that has been shown to encode the specificity for hormone recognition and binding. The G protein-coupled receptors share a common mode of intracellular signalling: They control the on/off state of a variety of trimeric G proteins (G{alpha}{beta}{gamma}) by stimulating the exchange of GDP for GTP on the {alpha} subunit (G{alpha}). The result is that G{alpha} or G{beta}{gamma}, after dissociation of the trimer, will interact with downstream effectors of the receptor. In the case of the TSH receptor, the main G protein involved is Gs, which activates adenylyl cyclase via Gs{alpha}. In some species, including man, the TSH receptor is also capable of activating phospholipase C (via Gq), thus stimulating the production of diacylglycerol and inositolphosphate (IP{sub 3}). However, higher concentrations of TSH are required to activate phospholipase C, compared with adenylyl cyclase. As a consequence, the main second messenger of TSH effects on the human thyroid is cyclic AMP. The present review will summarize recent findings identifying mutations of the TSH receptor gene as a cause for thyroid diseases. 59 refs., 4 figs.

Van Sande, J.; Parma, J.; Tonacchera, M. [and others] [and others

1995-09-01

113

SUMOylation regulates the chromatin occupancy and anti-proliferative gene programs of glucocorticoid receptor  

PubMed Central

In addition to the glucocorticoids, the glucocorticoid receptor (GR) is regulated by post-translational modifications, including SUMOylation. We have analyzed how SUMOylation influences the activity of endogenous GR target genes and the receptor chromatin binding by using isogenic HEK293 cells expressing wild-type GR (wtGR) or SUMOylation-defective GR (GR3KR). Gene expression profiling revealed that both dexamethasone up- and downregulated genes are affected by the GR SUMOylation and that the affected genes are significantly associated with pathways of cellular proliferation and survival. The GR3KR-expressing cells proliferated more rapidly, and their anti-proliferative response to dexamethasone was less pronounced than in the wtGR-expressing cells. ChIP-seq analyses indicated that the SUMOylation modulates the chromatin occupancy of GR on several loci associated with cellular growth in a fashion that parallels with their differential dexamethasone-regulated expression between the two cell lines. Moreover, chromatin SUMO-2/3 marks, which were associated with active GR-binding sites, showed markedly higher overlap with the wtGR cistrome than with the GR3KR cistrome. In sum, our results indicate that the SUMOylation does not simply repress the GR activity, but regulates the activity of the receptor in a target locus selective fashion, playing an important role in controlling the GR activity on genes influencing cell growth. PMID:24194604

Paakinaho, Ville; Kaikkonen, Sanna; Makkonen, Harri; Benes, Vladimir; Palvimo, Jorma J.

2014-01-01

114

The CAG Repeat within the Androgen Receptor Gene and its Relationship to Prostate Cancer  

Microsoft Academic Search

The length of a polymorphic CAG repeat sequence, occurring in the androgen receptor gene, is inversely correlated with transcriptional activity by the androgen receptor. Because heightened androgenic stimulation may increase risk of prostate cancer development and progression, we examined whether shorter CAG repeats in the androgen receptor gene are related to higher risk of prostate cancer. We conducted a nested

Edward Giovannucci; Meir J. Stampfer; Krishna Krithivas; Myles Brown; Adam Brufsky; James Talcott; Charles H. Hennekens; Philip W. Kantoff

1997-01-01

115

Enhancers Located within Two Introns of the Vitamin D Receptor Gene Mediate Transcriptional  

E-print Network

Enhancers Located within Two Introns of the Vitamin D Receptor Gene Mediate Transcriptional of 1,25-(OH)2D3 are medi- ated by the vitamin D receptor (VDR), a protein that binds to target genes. (Molecular Endo- crinology 20: 1231­1247, 2006) THE VITAMIN D RECEPTOR (VDR) is a member of a large

Pike, J. Wesley

116

Early vertebrate chromosome duplications and the evolution of the neuropeptide Y receptor gene regions  

Microsoft Academic Search

BACKGROUND: One of the many gene families that expanded in early vertebrate evolution is the neuropeptide (NPY) receptor family of G-protein coupled receptors. Earlier work by our lab suggested that several of the NPY receptor genes found in extant vertebrates resulted from two genome duplications before the origin of jawed vertebrates (gnathostomes) and one additional genome duplication in the actinopterygian

Tomas A Larsson; Frida Olsson; Gorel Sundstrom; Lars-Gustav Lundin; Sydney Brenner; Byrappa Venkatesh; Dan Larhammar

2008-01-01

117

Ghrelin receptor gene polymorphisms and body size in children and adults Garcia Edwin A. 1 ,*  

E-print Network

first authors Abstract Background The growth hormone secretagogue receptor type 1a gene ( ) encodes ; ALSPAC ; Ely Study Introduction The growth hormone secretagogue receptor type 1a gene ( ) encodes the cognate receptor of ghrelin, a gut hormone that regulatesGHSR food intake and pituitary growth hormone

Paris-Sud XI, Université de

118

Plant Receptor-Like Kinase Gene Family: Diversity, Function, and Signaling  

NSDL National Science Digital Library

A basic feature of all biological systems is the ability to sense and process information from chemical signals via cell-surface receptors. One prevalent class of receptors in both plants and animals is the receptor protein kinases. These proteins contain a signal-binding region located outside the cell linked to a region inside the cell called the protein kinase domain. The protein kinase domain transmits information to other cellular components by catalyzing the transfer of a phosphate group from adenosine triphosphate (ATP) to an amino acid residue on the target proteins. In animals and humans, the well-studied family of receptor tyrosine kinases (RTKs) mediates a wide range of signaling events at the cell surface. The importance of receptor protein kinases in plant biology was revealed by the discovery of a family of more than 400 genes coding for receptor-like kinases (RLKs) present in the recently sequenced genome of the model plant Arabidopsis. Unlike most animal RTKs, the plant RLKs use serine and threonine residues in proteins as targets for phosphorylation. Detailed studies of a handful of plant RLK genes have implicated them in the control of plant growth and development and in responses to pathogens. Multiple signals can be sensed by different RLKs, including peptides produced by neighboring cells, steroid hormones, and pathogen cell-wall proteins and carbohydrates. Major challenges for the future will include understanding the wide range of specific signaling functions performed by this large family of receptors and discovering how the information from this multitude of signal initiation points is integrated by the plant's cells.

Shin-Han Shiu (University of Wisconsin-Madison; The Department of Botany REV)

2001-12-18

119

Smallest bitter taste receptor (T2Rs) gene repertoire in carnivores.  

PubMed

Bitter taste reception is presumably associated with dietary selection, preventing animals from ingesting potentially harmful compounds. Accordingly, carnivores, who encounter these toxic substances less often, should have fewer genes associated with bitter taste reception compared with herbivores and omnivores. To investigate the genetic basis of bitter taste reception, we confirmed bitter taste receptor (T2R) genes previously found in the genome sequences of two herbivores (cow and horse), two omnivores (mouse and rat) and one carnivore (dog). We also identified, for the first time, the T2R repertoire from the genome of other four carnivore species (ferret, giant panda, polar bear and cat) and detected 17-20 bitter receptor genes from the five carnivore genomes, including 12-16 intact genes, 0-1 partial but putatively functional genes, and 3-8 pseudogenes. Both the intact T2R genes and the total T2R gene number among carnivores were the smallest among the tested species, supporting earlier speculations that carnivores have fewer T2R genes, herbivores an intermediate number, and omnivores the largest T2R gene repertoire. To further explain the genetic basis for this disparity, we constructed a phylogenetic tree, which showed most of the T2R genes from the five carnivores were one-to-one orthologs across the tree, suggesting that carnivore T2Rs were conserved among mammals. Similarly, the small carnivore T2R family size was likely due to rare duplication events. Collectively, these results strengthen arguments for the connection between T2R gene family size, diet and habit. PMID:23776004

Hu, Ling-Ling; Shi, Peng

2013-06-01

120

Control of transcriptional repression of the vitellogenin receptor gene in largemouth bass (Micropterus salmoides) by select estrogen receptors isotypes.  

PubMed

The vitellogenin receptor (Vtgr) plays an important role in fish reproduction. This receptor functions to incorporate vitellogenin (Vtg), a macromolecule synthesized and released from the liver in the bloodstream, into oocytes where it is processed into yolk. Although studies have focused on the functional role of Vtgr in fish, the mechanistic control of this gene is still unexplored. Here we report the identification and analysis of the first piscine 5' regulatory region of the vtgr gene which was cloned from largemouth bass (Micropterus salmoides). Using this putative promoter sequence, we investigated a role for hormones, including insulin and 17?-estradiol (E2), in transcriptional regulation through cell-based reporter assays. No effect of insulin was observed, however, E2 was able to repress transcriptional activity of the vtgr promoter through select estrogen receptor subtypes, Esr1 and Esr2a but not Esr2b. Electrophoretic mobility shift assay demonstrated that Esr1 likely interacts with the vtgr promoter region through half ERE and/or SP1 sites, in part. Finally we also show that ethinylestradiol (EE2), but not bisphenol-A (BPA), represses promoter activity similarly to E2. These results reveal for the first time that the Esr1 isoform may play an inhibitory role in the expression of LMB vtgr mRNA under the influence of E2, and potent estrogens such as EE2. In addition, this new evidence suggests that vtgr may be a target of select endocrine disrupting compounds through environmental exposures. PMID:25061109

Dominguez, Gustavo A; Bisesi, Joseph H; Kroll, Kevin J; Denslow, Nancy D; Sabo-Attwood, Tara

2014-10-01

121

Amplification of small molecule-inducible gene expression via tuning of intracellular receptor densities  

PubMed Central

Ligand-responsive transcription factors in prokaryotes found simple small molecule-inducible gene expression systems. These have been extensively used for regulated protein production and associated biosynthesis of fine chemicals. However, the promoter and protein engineering approaches traditionally used often pose significant restrictions to predictably and rapidly tune the expression profiles of inducible expression systems. Here, we present a new unified and rational tuning method to amplify the sensitivity and dynamic ranges of versatile small molecule-inducible expression systems. We employ a systematic variation of the concentration of intracellular receptors for transcriptional control. We show that a low density of the repressor receptor (e.g. TetR and ArsR) in the cell can significantly increase the sensitivity and dynamic range, whereas a high activator receptor (e.g. LuxR) density achieves the same outcome. The intracellular concentration of receptors can be tuned in both discrete and continuous modes by adjusting the strength of their cognate driving promoters. We exemplified this approach in several synthetic receptor-mediated sensing circuits, including a tunable cell-based arsenic sensor. The approach offers a new paradigm to predictably tune and amplify ligand-responsive gene expression with potential applications in synthetic biology and industrial biotechnology. PMID:25589545

Wang, Baojun; Barahona, Mauricio; Buck, Martin

2015-01-01

122

Ligand-based gene expression profiling reveals novel roles of glucocorticoid receptor in cardiac metabolism.  

PubMed

Recent studies have documented various roles of adrenal corticosteroid signaling in cardiac physiology and pathophysiology. It is known that glucocorticoids and aldosterone are able to bind glucocorticoid receptor (GR) and mineralocorticoid receptor, and these ligand-receptor interactions are redundant. It, therefore, has been impossible to delineate how these nuclear receptors couple with corticosteroid ligands and differentially regulate gene expression for operation of their distinct functions in the heart. Here, to particularly define the role of GR in cardiac muscle cells, we applied a ligand-based approach involving the GR-specific agonist cortivazol (CVZ) and the GR antagonist RU-486 and performed microarray analysis using rat neonatal cardiomyocytes. We indicated that glucocorticoids appear to be a major determinant of GR-mediated gene expression when compared with aldosterone. Moreover, expression profiles of these genes highlighted numerous roles of glucocorticoids in various aspects of cardiac physiology. At first, we identified that glucocorticoids, via GR, induce mRNA and protein expression of a transcription factor Kruppel-like factor 15 and its downstream target genes, including branched-chain aminotransferase 2, a key enzyme for amino acid catabolism in the muscle. CVZ treatment or overexpression of KLF15 decreased cellular branched-chain amino acid concentrations and introduction of small-interfering RNA against KLF15 cancelled these CVZ actions in cardiomyocytes. Second, glucocorticoid-GR signaling promoted gene expression of the enzymes involved in the prostaglandin biosynthesis, including cyclooxygenase-2 and phospholipase A2 in cardiomyocytes. Together, we may conclude that GR signaling should have distinct roles for maintenance of cardiac function, for example, in amino acid catabolism and prostaglandin biosynthesis in the heart. PMID:19293335

Yoshikawa, Noritada; Nagasaki, Masao; Sano, Motoaki; Tokudome, Satori; Ueno, Kazuko; Shimizu, Noriaki; Imoto, Seiya; Miyano, Satoru; Suematsu, Makoto; Fukuda, Keiichi; Morimoto, Chikao; Tanaka, Hirotoshi

2009-06-01

123

Perilipin, a critical regulator of fat storage and breakdown, is a target gene of estrogen receptor-related receptor {alpha}  

SciTech Connect

Perilipin is a protein localized on lipid droplet surfaces in adipocytes and steroidogenic cells, playing a central role in regulated lipolysis. Expression of the perilipin gene is markedly induced during adipogenesis. We found that transcription from the perilipin gene promoter is activated by an orphan nuclear receptor, estrogen receptor-related receptor (ERR){alpha}. A response element to this receptor was identified in the promoter region by a gene reporter assay, the electrophoretic-gel mobility-shift assay and the chromatin immunoprecipitation assay. Peroxisome proliferator-activated receptor {gamma} coactivator (PGC)-1{alpha} enhanced, whereas small heterodimer partner (SHP) repressed, the transactivating function of ERR{alpha} on the promoter. Thus, the perilipin gene expression is regulated by a transcriptional network controlling energy metabolism, substantiating the functional importance of perilipin in the maintenance of body energy balance.

Akter, Mst. Hasina; Yamaguchi, Tomohiro; Hirose, Fumiko [Graduate School of Life Science, Himeji Institute of Technology, University of Hyogo, 3-2-1 Koto, Kamigori, Hyogo 678-1297 (Japan); Osumi, Takashi [Graduate School of Life Science, Himeji Institute of Technology, University of Hyogo, 3-2-1 Koto, Kamigori, Hyogo 678-1297 (Japan)], E-mail: osumi@sci.u-hyogo.ac.jp

2008-04-11

124

Directed evolution of specific receptor-ligand pairs for use in the creation of gene switches  

Microsoft Academic Search

Despite their versatility and power in controlling gene regulation in nature, nuclear hormone receptors (NHRs) have largely eluded utility in heterologous gene regulation applications such as gene therapy and metabolic engineering. The main reason for this void is the pleiotropic interference of the receptor-ligand combination with regulatory networks in the host organism. In recent years, numerous strategies have been developed

Karuppiah Chockalingam; Zhilei Chen; John A. Katzenellenbogen; Huimin Zhao

2005-01-01

125

Analysis of the murine Dtk gene identifies conservation of genomic structure within a new receptor tyrosine kinase subfamily  

SciTech Connect

The receptor tyrosine kinase Dtk/Tyro 3/Sky/rse/brt/tif is a member of a new subfamily of receptors that also includes Axl/Ufo/Ark and Eyk/Mer. These receptors are characterized by the presence of two immunoglobulin-like loops and two fibronectin type III repeats in their extracellular domains. The structure of the murine Dtk gene has been determined. The gene consists of 21 exons that are distributed over 21 kb of genomic DNA. An isoform of Dtk is generated by differential splicing of exons from the 5{prime} region of the gene. The overall genomic structure of Dtk is virtually identical to that determined for the human UFO gene. This particular genomic organization is likely to have been duplicated and closely maintained throughout evolution. 38 refs., 3 figs., 1 tab.

Lewis, P.M.; Crosier, K.E.; Crosier, P.S. [Univ. of Auckland (New Zealand)] [and others] [Univ. of Auckland (New Zealand); and others

1996-01-01

126

Characterization of a dwarf gene in Brassica rapa , including the identification of a candidate gene  

Microsoft Academic Search

Dwarf genes have been valuable for improving harvestable yield of several crop plants and may be useful in oilseed Brassica. We evaluated a dwarf gene, dwf2, from Brassica rapa in order to determine its phenotypic effects and genetic characteristics. The dwf2 mutant was insensitive to exogenous GA 3 for both plant height and flowering time, suggesting that it is not

A. Muangprom; T. C. Osborn

2004-01-01

127

Expression analysis of the estrogen receptor target genes in renal cell carcinoma  

PubMed Central

The aim of the present study was to investigate the differentially expressed genes (DEGs) and target genes of the estrogen receptor (ER) in renal cell carcinoma. The data (GSE12090) were downloaded from the gene expression omnibus database. Data underwent preprocessing using the affy package for Bioconductor software, then the DEGs were selected via the significance analysis of microarray algorithm within the siggenes package. Subsequently, the DEGs underwent functional and pathway enrichment analysis using Database for Annotation Visualization and Integrated Discovery software. Following data analysis, transcriptional regulatory networks between the DEGs and transcription factors were constructed. Finally, the ER target genes were subjected to gene ontology enrichment analysis. A total of 215 DEGs were identified between the chromophobe renal cell carcinoma samples and the oncocytoma samples, including 126 upregulated and 89 downregulated genes. Functional enrichment analysis indicated that 25% of the DEGs were significantly enriched in functions associated with the plasma membrane. Among those DEGs, 105 were regulated by the ER. Further regulatory network analysis indicated that the ER was mainly involved in the regulation of oncogenes and tumor suppressor genes, including protease serine 8, claudin 7 and Ras-related protein Rab-25. In the present study, the identified ER target genes were demonstrated to be closely associated with tumor development; this knowledge may improve the understanding of the ER regulatory mechanisms during tumor development and promote the discovery of predictive markers for renal cell carcinoma. PMID:25351113

LIU, ZHIHONG; LU, YOU; HE, ZONGHAI; CHEN, LIBO; LU, YIPING

2015-01-01

128

Expression analysis of the estrogen receptor target genes in renal cell carcinoma.  

PubMed

The aim of the present study was to investigate the differentially expressed genes (DEGs) and target genes of the estrogen receptor (ER) in renal cell carcinoma. The data (GSE12090) were downloaded from the gene expression omnibus database. Data underwent preprocessing using the affy package for Bioconductor software, then the DEGs were selected via the significance analysis of microarray algorithm within the siggenes package. Subsequently, the DEGs underwent functional and pathway enrichment analysis using Database for Annotation Visualization and Integrated Discovery software. Following data analysis, transcriptional regulatory networks between the DEGs and transcription factors were constructed. Finally, the ER target genes were subjected to gene ontology enrichment analysis. A total of 215 DEGs were identified between the chromophobe renal cell carcinoma samples and the oncocytoma samples, including 126 upregulated and 89 downregulated genes. Functional enrichment analysis indicated that 25% of the DEGs were significantly enriched in functions associated with the plasma membrane. Among those DEGs, 105 were regulated by the ER. Further regulatory network analysis indicated that the ER was mainly involved in the regulation of oncogenes and tumor suppressor genes, including protease serine 8, claudin 7 and Ras-related protein Rab-25. In the present study, the identified ER target genes were demonstrated to be closely associated with tumor development; this knowledge may improve the understanding of the ER regulatory mechanisms during tumor development and promote the discovery of predictive markers for renal cell carcinoma. PMID:25351113

Liu, Zhihong; Lu, You; He, Zonghai; Chen, Libo; Lu, Yiping

2015-01-01

129

Polymorphism and genetic mapping of the human oxytocin receptor gene on chromosome 3  

SciTech Connect

Centrally administered oxytocin has been reported to facilitate affiliative and social behaviors, in functional harmony with its well-known peripheral effects on uterine contraction and milk ejection. The biological effects of oxytocin could be perturbed by mutations occurring in the sequence of the oxytocin receptor gene, and it would be of interest to establish the position of this gene on the human linkage map. Therefore we identified a polymorphism at the human oxytocin receptor gene. A portion of the 3{prime} untranslated region containing a 30 bp CA repeat was amplified by polymerase chain reaction (PCR), revealing a polymorphism with two alleles occurring with frequencies of 0.77 and 0.23 in a sample of Caucasian CEPH parents (n = 70). The CA repeat polymorphism we detected was used to map the human oxytocin receptor to chromosome 3p25-3p26, in a region which contains several important genes, including loci for Von Hippel-Lindau disease (VHL) and renal cell carcinoma. 53 refs., 2 figs., 1 tab.

Michelini, S.; Urbanek, M.; Goldman, D. [National Institute of Health-National Institute of Alcohol Abuse and Alcoholism, Rockville, MD (United States)] [and others

1995-06-19

130

Gene expression of NMDA receptor subunits in the cerebellum of elderly patients with schizophrenia  

Microsoft Academic Search

To determine if NMDA receptor alterations are present in the cerebellum in schizophrenia, we measured NMDA receptor binding\\u000a and gene expression of the NMDA receptor subunits in a post-mortem study of elderly patients with schizophrenia and non-affected\\u000a subjects. Furthermore, we assessed influence of genetic variation in the candidate gene neuregulin-1 (NRG1) on the expression of the NMDA receptor in an

Andrea Schmitt; Jiri Koschel; Mathias Zink; Manfred Bauer; Clemens Sommer; Josef Frank; Jens Treutlein; Thomas Schulze; Thomas Schneider-Axmann; Eleni Parlapani; Marcella Rietschel; Peter Falkai; Fritz A. Henn

2010-01-01

131

Evolution of dopamine receptor genes of the D1 class in vertebrates.  

PubMed

The receptors of the dopamine neurotransmitter belong to two unrelated classes named D1 and D2. For the D1 receptor class, only two subtypes are found in mammals, the D1A and D1B, receptors, whereas additional subtypes, named D1C, D1D, and D1X, have been found in other vertebrate species. Here, we analyzed molecular phylogeny, gene synteny, and gene expression pattern of the D1 receptor subtypes in a large range of vertebrate species, which leads us to propose a new view of the evolution of D1 dopamine receptor genes. First, we show that D1C and D1D receptor sequences are encoded by orthologous genes. Second, the previously identified Cypriniform D1X sequence is a teleost-specific paralog of the D1B sequences found in all groups of jawed vertebrates. Third, zebrafish and several sauropsid species possess an additional D1-like gene, which is likely to form another orthology group of vertebrate ancestral genes, which we propose to name D1E. Ancestral jawed vertebrates are thus likely to have possessed four classes of D1 receptor genes-D1A, D1B(X), D1C(D), and D1E-which arose from large-scale gene duplications. The D1C receptor gene would have been secondarily lost in the mammalian lineage, whereas the D1E receptor gene would have been lost independently in several lineages of modern vertebrates. The D1A receptors are well conserved throughout jawed vertebrates, whereas sauropsid D1C receptors have rapidly diverged, to the point that they were misidentified as D1D. The functional significance of the D1C receptor loss is not known. It is possible that the function may have been substituted with D1A or D1B receptors in mammals, following the disappearance of D1C receptors in these species. PMID:23197594

Yamamoto, Kei; Mirabeau, Olivier; Bureau, Charlotte; Blin, Maryline; Michon-Coudouel, Sophie; Demarque, Michaël; Vernier, Philippe

2013-04-01

132

Enhancement of gene transactivation activity of androgen receptor by hepatitis B virus X protein  

SciTech Connect

Hepatitis B virus (HBV) X protein (HBx) is a regulatory protein that is required for efficient replication of HBV in its natural host. In this report, we demonstrate by co-immunoprecipitation experiments that HBx can physically bind to the androgen receptor (AR), which is a nuclear hormone receptor that is expressed in many different tissues including the liver. This observation is further supported by confocal microscopy, which reveals that HBx can alter the subcellular localization of the AR both in the presence and in the absence of dihydrotestosterone (DHT). Further studies indicate that HBx can enhance the gene transactivation activity of AR by enhancing its DNA binding activity in a DHT-dependent manner. However, HBx does not remain associated with AR on the DNA. As AR can regulate the expression of a number of cellular genes, our results raise the possibility that HBV pathogenesis may be mediated in part via the interaction between HBx and AR.

Zheng Yanyan [Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, HMR-401, Los Angeles, CA 90033 (United States); Chen Wenling [Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, HMR-401, Los Angeles, CA 90033 (United States); Ma, W.-L. Maverick [George Whipple Lab for Cancer Research, Department of Pathology, Urology, Radiation Oncology and the Cancer Center, University of Rochester Medical Center, Rochester, NY (United States); Chang Chawnshang [George Whipple Lab for Cancer Research, Department of Pathology, Urology, Radiation Oncology and the Cancer Center, University of Rochester Medical Center, Rochester, NY (United States); Ou, J.-H. James [Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, HMR-401, Los Angeles, CA 90033 (United States)]. E-mail: jamesou@hsc.usc.edu

2007-07-05

133

Identification of Modulators of the Nuclear Receptor Peroxisome Proliferator-Activated Receptor ? (PPAR?) in a Mouse Liver Gene Expression Compendium  

PubMed Central

The nuclear receptor family member peroxisome proliferator-activated receptor ? (PPAR?) is activated by therapeutic hypolipidemic drugs and environmentally-relevant chemicals to regulate genes involved in lipid transport and catabolism. Chronic activation of PPAR? in rodents increases liver cancer incidence, whereas suppression of PPAR? activity leads to hepatocellular steatosis. Analytical approaches were developed to identify biosets (i.e., gene expression differences between two conditions) in a genomic database in which PPAR? activity was altered. A gene expression signature of 131 PPAR?-dependent genes was built using microarray profiles from the livers of wild-type and PPAR?-null mice after exposure to three structurally diverse PPAR? activators (WY-14,643, fenofibrate and perfluorohexane sulfonate). A fold-change rank-based test (Running Fisher’s test (p-value ? 10-4)) was used to evaluate the similarity between the PPAR? signature and a test set of 48 and 31 biosets positive or negative, respectively for PPAR? activation; the test resulted in a balanced accuracy of 98%. The signature was then used to identify factors that activate or suppress PPAR? in an annotated mouse liver/primary hepatocyte gene expression compendium of ~1850 biosets. In addition to the expected activation of PPAR? by fibrate drugs, di(2-ethylhexyl) phthalate, and perfluorinated compounds, PPAR? was activated by benzofuran, galactosamine, and TCDD and suppressed by hepatotoxins acetaminophen, lipopolysaccharide, silicon dioxide nanoparticles, and trovafloxacin. Additional factors that activate (fasting, caloric restriction) or suppress (infections) PPAR? were also identified. This study 1) developed methods useful for future screening of environmental chemicals, 2) identified chemicals that activate or suppress PPAR?, and 3) identified factors including diets and infections that modulate PPAR? activity and would be hypothesized to affect chemical-induced PPAR? activity. PMID:25689681

Oshida, Keiyu; Vasani, Naresh; Thomas, Russell S.; Applegate, Dawn; Rosen, Mitch; Abbott, Barbara; Lau, Christopher; Guo, Grace; Aleksunes, Lauren M.; Klaassen, Curtis; Corton, J. Christopher

2015-01-01

134

Identification of Modulators of the Nuclear Receptor Peroxisome Proliferator-Activated Receptor ? (PPAR?) in a Mouse Liver Gene Expression Compendium.  

PubMed

The nuclear receptor family member peroxisome proliferator-activated receptor ? (PPAR?) is activated by therapeutic hypolipidemic drugs and environmentally-relevant chemicals to regulate genes involved in lipid transport and catabolism. Chronic activation of PPAR? in rodents increases liver cancer incidence, whereas suppression of PPAR? activity leads to hepatocellular steatosis. Analytical approaches were developed to identify biosets (i.e., gene expression differences between two conditions) in a genomic database in which PPAR? activity was altered. A gene expression signature of 131 PPAR?-dependent genes was built using microarray profiles from the livers of wild-type and PPAR?-null mice after exposure to three structurally diverse PPAR? activators (WY-14,643, fenofibrate and perfluorohexane sulfonate). A fold-change rank-based test (Running Fisher's test (p-value ? 10-4)) was used to evaluate the similarity between the PPAR? signature and a test set of 48 and 31 biosets positive or negative, respectively for PPAR? activation; the test resulted in a balanced accuracy of 98%. The signature was then used to identify factors that activate or suppress PPAR? in an annotated mouse liver/primary hepatocyte gene expression compendium of ~1850 biosets. In addition to the expected activation of PPAR? by fibrate drugs, di(2-ethylhexyl) phthalate, and perfluorinated compounds, PPAR? was activated by benzofuran, galactosamine, and TCDD and suppressed by hepatotoxins acetaminophen, lipopolysaccharide, silicon dioxide nanoparticles, and trovafloxacin. Additional factors that activate (fasting, caloric restriction) or suppress (infections) PPAR? were also identified. This study 1) developed methods useful for future screening of environmental chemicals, 2) identified chemicals that activate or suppress PPAR?, and 3) identified factors including diets and infections that modulate PPAR? activity and would be hypothesized to affect chemical-induced PPAR? activity. PMID:25689681

Oshida, Keiyu; Vasani, Naresh; Thomas, Russell S; Applegate, Dawn; Rosen, Mitch; Abbott, Barbara; Lau, Christopher; Guo, Grace; Aleksunes, Lauren M; Klaassen, Curtis; Corton, J Christopher

2015-01-01

135

The nuclear receptor Liver Receptor Homolog-1 is an Estrogen Receptor target gene  

E-print Network

role for LRH-1 has been discovered in tumor progression, giving LRH-1 potential transforming functions of MCF7 cells. Finally, LRH-1 protein expression was detected by immunohistochemistry in tumor cells in granulosa cells and corpus luteum of the ovary, suggesting potential functions for this nuclear receptor

Paris-Sud XI, Université de

136

Evolutionary dynamics of olfactory and other chemosensory receptor genes in vertebrates  

PubMed Central

The numbers of functional olfactory receptor (OR) genes in humans and mice are about 400 and 1,000 respectively. In both humans and mice, these genes exist as genomic clusters and are scattered over almost all chromosomes. The difference in the number of genes between the two species is apparently caused by massive inactivation of OR genes in the human lineage and a substantial increase of OR genes in the mouse lineage after the human–mouse divergence. Compared with mammals, fishes have a much smaller number of OR genes. However, the OR gene family in fishes is much more divergent than that in mammals. Fishes have many different groups of genes that are absent in mammals, suggesting that the mammalian OR gene family is characterized by the loss of many group genes that existed in the ancestor of vertebrates and the subsequent expansion of specific groups of genes. Therefore, this gene family apparently changed dynamically depending on the evolutionary lineage and evolved under the birth-and-death model of evolution. Study of the evolutionary changes of two gene families for vomeronasal receptors and two gene families for taste receptors, which are structurally similar, but remotely related to OR genes, showed that some of the gene families evolved in the same fashion as the OR gene family. It appears that the number and types of genes in chemosensory receptor gene families have evolved in response to environmental needs, but they are also affected by fortuitous factors. PMID:16607462

Niimura, Yoshihito

2007-01-01

137

Novel transcripts of the estrogen receptor ?? gene in channel catfish  

USGS Publications Warehouse

Complementary DNA libraries from liver and ovary of an immature female channel catfish were screened with a homologous ER?? cDNA probe. The hepatic library yielded two new channel catfish ER cDNAs that encode N-terminal ER?? variants of different sizes. Relative to the catfish ER?? (medium size; 581 residues) previously reported, these new cDNAs encode Long-ER?? (36 residues longer) and Short-ER?? (389 residues shorter). The 5???-end of Long-ER?? cDNA is identical to that of Medium-ER?? but has an additional 503-bp segment with an upstream, in-frame translation-start codon. Recombinant Long-ER?? binds estrogen with high affinity (Kd = 3.4 nM), similar to that previously reported for Medium-ER?? but lower than reported for catfish ER??. Short-ER?? cDNA encodes a protein that lacks most of the receptor protein and does not bind estrogen. Northern hybridization confirmed the existence of multiple hepatic ER?? RNAs that include the size range of the ER?? cDNAs obtained from the libraries as well as additional sizes. Using primers for RT-PCR that target locations internal to the protein-coding sequence, we also established the presence of several ER?? cDNA variants with in-frame insertions in the ligand-binding and DNA-binding domains and in-frame or out-of-frame deletions in the ligand-binding domain. These internal variants showed patterns of expression that differed between the ovary and liver. Further, the ovarian library yielded a full-length, ER?? antisense cDNA containing a poly(A) signal and tail. A limited survey of histological preparations from juvenile catfish by in situ hybridization using directionally synthesized cRNA probes also suggested the expression of ER?? antisense RNA in a tissue-specific manner. In conclusion, channel catfish seemingly have three broad classes of ER?? mRNA variants: those encoding N-terminal truncated variants, those encoding internal variants (including C-terminal truncated variants), and antisense mRNA. The sense variants may encode functional ER?? or related proteins that modulate ER?? or ER?? activity. The existence of ER antisense mRNA is reported in this study for the first time. Its role may be to participate in the regulation of ER gene expression. ?? 2000 Academic Press.

Patino, R.; Xia, Z.; Gale, W.L.; Wu, C.; Maule, A.G.; Chang, X.

2000-01-01

138

Deep Conservation of Genes Required for Both Drosophila melanogaster and Caenorhabditis elegans Sleep Includes a Role for Dopaminergic Signaling  

PubMed Central

Objectives: Cross-species conservation of sleep-like behaviors predicts the presence of conserved molecular mechanisms underlying sleep. However, limited experimental evidence of conservation exists. Here, this prediction is tested directly. Measurements and Results: During lethargus, Caenorhabditis elegans spontaneously sleep in short bouts that are interspersed with bouts of spontaneous locomotion. We identified 26 genes required for Drosophila melanogaster sleep. Twenty orthologous C. elegans genes were selected based on similarity. Their effect on C. elegans sleep and arousal during the last larval lethargus was assessed. The 20 most similar genes altered both the quantity of sleep and arousal thresholds. In 18 cases, the direction of change was concordant with Drosophila studies published previously. Additionally, we delineated a conserved genetic pathway by which dopamine regulates sleep and arousal. In C. elegans neurons, G-alpha S, adenylyl cyclase, and protein kinase A act downstream of D1 dopamine receptors to regulate these behaviors. Finally, a quantitative analysis of genes examined herein revealed that C. elegans arousal thresholds were directly correlated with amount of sleep during lethargus. However, bout duration varies little and was not correlated with arousal thresholds. Conclusions: The comprehensive analysis presented here suggests that conserved genes and pathways are required for sleep in invertebrates and, likely, across the entire animal kingdom. The genetic pathway delineated in this study implicates G-alpha S and previously known genes downstream of dopamine signaling in sleep. Quantitative analysis of various components of quiescence suggests that interdependent or identical cellular and molecular mechanisms are likely to regulate both arousal and sleep entry. Citation: Singh K, Ju JY, Walsh MB, Dilorio MA, Hart AC. Deep conservation of genes required for both Drosophila melanogaster and Caenorhabditis elegans sleep includes a role for dopaminergic signaling. SLEEP 2014;37(9):1439-1451. PMID:25142568

Singh, Komudi; Ju, Jennifer Y.; Walsh, Melissa B.; DiIorio, Michael A.; Hart, Anne C.

2014-01-01

139

Receptor protein kinase gene encoded at the self-incompatibility locus  

DOEpatents

Described herein is a S receptor kinase gene (SRK), derived from the S locus in Brassica oleracea, having a extracellular domain highly similar to the secreted product of the S-locus glycoprotein gene.

Nasrallah, June B. (Ithaca, NY); Nasrallah, Mikhail E. (Ithaca, NY); Stein, Joshua (Cortland, NY)

1996-01-01

140

The dopamine D3 receptor gene and posttraumatic stress disorder.  

PubMed

The dopamine D3 receptor (DRD3) gene has been implicated in schizophrenia, autism, and substance use-disorders and is related to emotion reactivity, executive functioning, and stress-responding, processes impaired in posttraumatic stress disorder (PTSD). The aim of this candidate gene study was to evaluate DRD3 polymorphisms for association with PTSD. The discovery sample was trauma-exposed White, non-Hispanic U.S. veterans and their trauma-exposed intimate partners (N = 491); 60.3% met criteria for lifetime PTSD. The replication sample was 601 trauma-exposed African American participants living in Detroit, Michigan; 23.6% met criteria for lifetime PTSD. Genotyping was based on high-density bead chips. In the discovery sample, 4 single nucleotide polymorphisms (SNPs), rs2134655, rs201252087, rs4646996, and rs9868039, showed evidence of association with PTSD and withstood correction for multiple testing. The minor alleles were associated with reduced risk for PTSD (OR range = 0.59 to 0.69). In the replication sample, rs2251177, located 149 base pairs away from the most significant SNP in the discovery sample, was nominally associated with PTSD in men (OR = 0.32). Although the precise role of the D3 receptor in PTSD is not yet known, its role in executive functioning and emotional reactivity, and the sensitivity of the dopamine system to environmental stressors could potentially explain this association. PMID:25158632

Wolf, Erika J; Mitchell, Karen S; Logue, Mark W; Baldwin, Clinton T; Reardon, Annemarie F; Aiello, Alison; Galea, Sandro; Koenen, Karestan C; Uddin, Monica; Wildman, Derek; Miller, Mark W

2014-08-01

141

Alteration of Gene Expression Profiling Including GPR174 and GNG2 is Associated with Vasovagal Syncope.  

PubMed

Vasovagal syncope (VVS) causes accidental harm for susceptible patients. However, pathophysiology of this disorder remains largely unknown. In an effort to understanding of molecular mechanism for VVS, genome-wide gene expression profiling analyses were performed on VVS patients at syncope state. A total of 66 Type 1 VVS child patients and the same number healthy controls were enrolled in this study. Peripheral blood RNAs were isolated from all subjects, of which 10 RNA samples were randomly selected from each groups for gene expression profile analysis using Gene ST 1.0 arrays (Affymetrix). The results revealed that 103 genes were differently expressed between the patients and controls. Significantly, two G-proteins related genes, GPR174 and GNG2 that have not been related to VVS were among the differently expressed genes. The microarray results were confirmed by qRT-PCR in all the tested individuals. Ingenuity pathway analysis and gene ontology annotation study showed that the differently expressed genes are associated with stress response and apoptosis, suggesting that the alteration of some gene expression including G-proteins related genes is associated with VVS. This study provides new insight into the molecular mechanism of VVS and would be helpful to further identify new molecular biomarkers for the disease. PMID:25367286

Huang, Yu-Juan; Zhou, Zai-Wei; Xu, Miao; Ma, Qing-Wen; Yan, Jing-Bin; Wang, Jian-Yi; Zhang, Quo-Qin; Huang, Min; Bao, Liming

2015-03-01

142

Dopamine D1 Receptors, Regulation of Gene Expression in the Brain, and Neurodegeneration  

PubMed Central

Dopamine (DA), the most abundant catecholamine in the basal ganglia, participates in the regulation of motor functions and of cognitive processes such as learning and memory. Abnormalities in dopaminergic systems are thought to be the bases for some neuropsychiatric disorders including addiction, Parkinson’s disease, and Schizophrenia. DA exerts its arrays of functions via stimulation of D1-like (D1 and D5) and D2-like (D2, D3, and D4) DA receptors which are located in various regions of the brain. The DA D1 and D2 receptors are very abundant in the basal ganglia where they exert their functions within separate neuronal cell types. The present paper focuses on a review of the effects of stimulation of DA D1 receptors on diverse signal transduction pathways and gene expression patterns in the brain. We also discuss the possible involvement of the DA D1 receptors in DA-mediated toxic effects observed both in vitro and in vivo. Future studies using more selective agonist and antagonist agents and the use of genetically modified animals should help to further clarify the role of these receptors in the normal physiology and in pathological events that involve DA. PMID:20632973

Cadet, Jean Lud; Jayanthi, Subramaniam; McCoy, Michael T.; Beauvais, Genevieve; Cai, Ning Sheng

2013-01-01

143

Characterization of a mouse laminin receptor gene homologous to the human blood group Lutheran gene  

Microsoft Academic Search

The human Lutheran (Lu) blood group antigens are carried by two glycoproteins (gps) that belong to the immunoglobulin (Ig)\\u000a superfamily. These gps represent adhesion molecules that function as the unique erythroid receptors for laminin. We report\\u000a here the cloning and functional expression of the orthologous mouse Lu mRNA as well as the genomic organization of the mouse Lu gene. The

Cécile Rahuel; Yves Colin; Dominique Goossens; P. Gane; W. El Nemer; J. P. Cartron; C. Le Van Kim

1999-01-01

144

RESEARCH ARTICLE Open Access Dynamic evolution of the GnRH receptor gene  

E-print Network

RH receptor genes sequenced exhib- ited expression restricted to the pituitary gland in mice and rats [5 family. First, the "mammalian" pituitary type GnRH receptor, which is the sole GnRH receptor in humans- tide produced by neurons in the hypothalamic-preoptic area in vertebrates; it causes pituitary

Eisthen, Heather L.

145

Paradata for 'ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-? and constitutively active receptor induced gene expression'  

NSDL National Science Digital Library

This record contains paradata for the resource 'ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-? and constitutively active receptor induced gene expression'

146

Noninvasive Repetitive Imaging of Somatostatin Receptor 2 Gene Transfer with Positron Emission Tomography  

PubMed Central

Abstract Noninvasive in vivo imaging of gene expression is desirable to monitor gene transfer in both animal models and humans. Reporter transgenes with low endogenous expression levels are instrumental to this end. The human somatostatin receptor 2 (hSSTR2) has low expression levels in a variety of tissues, including muscle and liver. We tested the possibility of noninvasively and quantitatively monitoring hSSTR2 transgene expression, following adeno-associated viral (AAV) vector-mediated gene delivery to murine muscle and liver by positron emission tomography (PET) using 68gallium-DOTA-Tyr3-Thr8-octreotate (68Ga-DOTATATE) as a highly specific SSTR2 ligand. Repetitive PET imaging showed hSSTR2 signal up to 6 months, which corresponds to the last time point of the analysis, after gene delivery in both transduced tissues. The levels of tracer accumulation measured in muscle and liver after gene delivery were significantly higher than in control tissues and correlated with the doses of AAV vector administered. As repetitive, quantitative, noninvasive imaging of AAV-mediated SSTR2 gene transfer to muscle and liver is feasible and efficient using PET, we propose this system to monitor the expression of therapeutic genes coexpressed with SSTR2. PMID:20825281

Cotugno, Gabriella; Aurilio, Michela; Annunziata, Patrizia; Capalbo, Anita; Faella, Armida; Rinaldi, Valentina; Strisciuglio, Caterina; Di Tommaso, Maurizio

2011-01-01

147

Noninvasive repetitive imaging of somatostatin receptor 2 gene transfer with positron emission tomography.  

PubMed

Noninvasive in vivo imaging of gene expression is desirable to monitor gene transfer in both animal models and humans. Reporter transgenes with low endogenous expression levels are instrumental to this end. The human somatostatin receptor 2 (hSSTR2) has low expression levels in a variety of tissues, including muscle and liver. We tested the possibility of noninvasively and quantitatively monitoring hSSTR2 transgene expression, following adeno-associated viral (AAV) vector-mediated gene delivery to murine muscle and liver by positron emission tomography (PET) using (68)gallium-DOTA-Tyr(3)-Thr(8)-octreotate ((68)Ga-DOTATATE) as a highly specific SSTR2 ligand. Repetitive PET imaging showed hSSTR2 signal up to 6 months, which corresponds to the last time point of the analysis, after gene delivery in both transduced tissues. The levels of tracer accumulation measured in muscle and liver after gene delivery were significantly higher than in control tissues and correlated with the doses of AAV vector administered. As repetitive, quantitative, noninvasive imaging of AAV-mediated SSTR2 gene transfer to muscle and liver is feasible and efficient using PET, we propose this system to monitor the expression of therapeutic genes coexpressed with SSTR2. PMID:20825281

Cotugno, Gabriella; Aurilio, Michela; Annunziata, Patrizia; Capalbo, Anita; Faella, Armida; Rinaldi, Valentina; Strisciuglio, Caterina; Di Tommaso, Maurizio; Aloj, Luigi; Auricchio, Alberto

2011-02-01

148

Chromatin Remodeling by the T Cell Receptor (Tcr)-? Gene Enhancer during Early T Cell Development  

PubMed Central

Gene targeting studies have shown that T cell receptor (TCR)-? gene expression and recombination are inhibited after deletion of an enhancer (E?) located at the 3? end of the ?500-kb TCR-? locus. Using knockout mouse models, we have measured, at different regions throughout the TCR-? locus, the effects of E? deletion on molecular parameters believed to reflect epigenetic changes associated with the control of gene activation, including restriction endonuclease access to chromosomal DNA, germline transcription, DNA methylation, and histone H3 acetylation. Our results demonstrate that, in early developing thymocytes, E? contributes to major chromatin remodeling directed to an ?25-kb upstream domain comprised of the D?-J? locus regions. Accordingly, treatment of E?-deleted thymocytes with the histone deacetylase inhibitor trichostatin A relieved the block in TCR-? gene expression and promoted recombination within the D?-J? loci. Unexpectedly, however, epigenetic processes at distal V? genes on the 5? side of the locus and at the 3? proximal V?14 gene appear to be less dependent on E?, suggesting that E? activity is confined to a discrete region of the TCR-? locus. These findings have implications with respect to the developmental control of TCR-? gene recombination, and the process of allelic exclusion at this locus. PMID:10974029

Mathieu, Noëlle; Hempel, William M.; Spicuglia, Salvatore; Verthuy, Christophe; Ferrier, Pierre

2000-01-01

149

The Dopamine D2 Receptor Gene, Perceived Parental Support, and Adolescent Loneliness: Longitudinal Evidence for Gene-Environment Interactions  

ERIC Educational Resources Information Center

Background: Loneliness is a common problem in adolescence. Earlier research focused on genes within the serotonin and oxytocin systems, but no studies have examined the role of dopamine-related genes in loneliness. In the present study, we focused on the dopamine D2 receptor gene (DRD2). Methods: Associations among the DRD2, sex, parental support,…

van Roekel, Eeske; Goossens, Luc; Scholte, Ron H. J.; Engels, Rutger C. M. E.; Verhagen, Maaike

2011-01-01

150

Transcriptional Characterization of Porcine Leptin and Leptin Receptor Genes  

PubMed Central

The leptin (LEP) and its receptor (LEPR) regulate food intake and energy balance through hypothalamic signaling. However, the LEP-LEPR axis seems to be more complex and its expression regulation has not been well described. In pigs, LEP and LEPR genes have been widely studied due to their relevance. Previous studies reported significant effects of SNPs located in both genes on growth and fatness traits. The aim of this study was to determine the expression profiles of LEP and LEPR across hypothalamic, adipose, hepatic and muscle tissues in Iberian x Landrace backcrossed pigs and to analyze the effects of gene variants on transcript abundance. To our knowledge, non porcine LEPR isoforms have been described rather than LEPRb. A short porcine LEPR isoform (LEPRa), that encodes a protein lacking the intracellular residues responsible of signal transduction, has been identified for the first time. The LEPRb isoform was only quantifiable in hypothalamus while LEPRa appeared widely expressed across tissues, but at higher levels in liver, suggesting that both isoforms would develop different roles. The unique LEP transcript showed expression in backfat and muscle. The effects of gene variants on transcript expression revealed interesting results. The LEPRc.1987C>T polymorphism showed opposite effects on LEPRb and LEPRa hypothalamic expression. In addition, one out of the 16 polymorphisms identified in the LEPR promoter region revealed high differential expression in hepatic LEPRa. These results suggest a LEPR isoform-specific regulation at tissue level. Conversely, non-differential expression of LEP conditional on the analyzed polymorphisms could be detected, indicating that its regulation is likely affected by other mechanisms rather than gene sequence variants. The present study has allowed a transcriptional characterization of LEP and LEPR isoforms on a range of tissues. Their expression patterns seem to indicate that both molecules develop peripheral roles apart from their known hypothalamic signal transduction function. PMID:23824082

Pérez-Montarelo, Dafne; Fernández, Almudena; Barragán, Carmen; Noguera, Jose L.; Folch, Josep M.; Rodríguez, M. Carmen; Óvilo, Cristina; Silió, Luis; Fernández, Ana I.

2013-01-01

151

Transcriptional Characterization of Porcine Leptin and Leptin Receptor Genes.  

PubMed

The leptin (LEP) and its receptor (LEPR) regulate food intake and energy balance through hypothalamic signaling. However, the LEP-LEPR axis seems to be more complex and its expression regulation has not been well described. In pigs, LEP and LEPR genes have been widely studied due to their relevance. Previous studies reported significant effects of SNPs located in both genes on growth and fatness traits. The aim of this study was to determine the expression profiles of LEP and LEPR across hypothalamic, adipose, hepatic and muscle tissues in Iberian x Landrace backcrossed pigs and to analyze the effects of gene variants on transcript abundance. To our knowledge, non porcine LEPR isoforms have been described rather than LEPRb. A short porcine LEPR isoform (LEPRa), that encodes a protein lacking the intracellular residues responsible of signal transduction, has been identified for the first time. The LEPRb isoform was only quantifiable in hypothalamus while LEPRa appeared widely expressed across tissues, but at higher levels in liver, suggesting that both isoforms would develop different roles. The unique LEP transcript showed expression in backfat and muscle. The effects of gene variants on transcript expression revealed interesting results. The LEPRc.1987C>T polymorphism showed opposite effects on LEPRb and LEPRa hypothalamic expression. In addition, one out of the 16 polymorphisms identified in the LEPR promoter region revealed high differential expression in hepatic LEPRa. These results suggest a LEPR isoform-specific regulation at tissue level. Conversely, non-differential expression of LEP conditional on the analyzed polymorphisms could be detected, indicating that its regulation is likely affected by other mechanisms rather than gene sequence variants. The present study has allowed a transcriptional characterization of LEP and LEPR isoforms on a range of tissues. Their expression patterns seem to indicate that both molecules develop peripheral roles apart from their known hypothalamic signal transduction function. PMID:23824082

Pérez-Montarelo, Dafne; Fernández, Almudena; Barragán, Carmen; Noguera, Jose L; Folch, Josep M; Rodríguez, M Carmen; Ovilo, Cristina; Silió, Luis; Fernández, Ana I

2013-01-01

152

Sexually dimorphic effects of oxytocin receptor gene (OXTR ) variants on Harm Avoidance  

PubMed Central

Background Recent research has suggested that oxytocin receptor gene (OXTR) variants may account for individual differences in social behavior, the effects of stress and parenting styles. Little is known, however, on a putative role of the gene in heritable temperamental traits. Methods We addressed effects of two common OXTR variants, rs237900 and rs237902, on personality dimensions in 99 healthy subjects using the Temperament and Character Inventory. Results When sex was controlled for and an OXTR genotype*sex interaction term was included in the regression model, 11% of the variance in Harm Avoidance could be explained (uncorrected p???0.01). Female carriers of the minor alleles scored highest, and a novel A217T mutation emerged in the most harm avoidant male participant. Conclusions Findings lend support to a modulatory effect of common OXTR variants on Harm Avoidance in healthy caucasian women and invite resequencing of the gene in anxiety phenotypes to identify more explanatory functional variation. PMID:22846218

2012-01-01

153

Migraine association and linkage analyses of the human 5-hydroxytryptamine (5HT 2A) receptor gene  

E-print Network

Migraine association and linkage analyses of the human 5-hydroxytryptamine (5HT 2A) receptor gene. Migraine association and linkage analyses of the human 5-hydroxytryptamine (5HT2A) receptor gene predominantly serves as an inhibitory neurotransmitter in the brain, has long been implicated in migraine

Nyholt, Dale R.

154

Polymorphism of the Androgen Receptor Gene is Associated with Male Pattern Baldness  

Microsoft Academic Search

The common heritable loss of scalp hair known as male pattern baldness or androgenetic alopecia affects up to 80% of males by age 80. A balding scalp is characterized by high levels of the potent androgen dihydrotestosterone and increased expression of the androgen receptor gene. To determine if the androgen receptor gene is associated with male pattern baldness, we compared

Justine A. Ellis; Margaret Stebbing; Stephen B. Harrap

2001-01-01

155

Dramatic variation of the vomeronasal pheromone receptor gene repertoire among five orders  

E-print Network

Dramatic variation of the vomeronasal pheromone receptor gene repertoire among five orders 25, 2005 (received for review January 15, 2005) Pheromones are chemicals emitted and sensed by the vomeronasal organ (VNO). Pheromone receptors in the mammalian VNO are encoded by the V1R and V2R gene

Zhang, Jianzhi

156

BRIEF REPORT: Ghrelin receptor gene polymorphisms and body size in children and adults  

E-print Network

,version1-20Aug2008 #12;Page 4 Introduction The growth hormone secretagogue receptor type 1a gene (GHSR receptor, body mass index, gene, growth, ALSPAC, Ely Study Word Count: 1899 words Author Disclosure Summary.ong@mrc-epid.cam.ac.uk inserm-00311659,version1-20Aug2008 #12;Page 3 Abstract Background: The growth hormone secretagogue

Paris-Sud XI, Université de

157

Msx1 Homeodomain Protein Represses the GSU and GnRH Receptor Genes During Gonadotrope  

E-print Network

(SF)1, then GnRH receptor (Gn- RHR), and finally, the appearance of the LH and FSH subunits on e16Msx1 Homeodomain Protein Represses the GSU and GnRH Receptor Genes During Gonadotrope Development represses transcription of lineage-specific pituitary genes such as the common -glycopro- tein subunit ( GSU

Mellon, Pamela L.

158

Trans-activator gene of HTLV-II induces IL-2 receptor and IL-2 cellular gene expression.  

PubMed

The human T-lymphotropic viruses types I and II (HTLV-I and -II) have been etiologically linked with certain T-cell leukemias and lymphomas that characteristically display membrane receptors for interleukin-2. The relation of these viruses to this growth factor receptor has remained unexplained. It is demonstrated here that introduction of the trans-activator (tat) gene of HTLV-II into the Jurkat T-lymphoid cell line results in the induction of both interleukin-2 receptor and interleukin-2 gene expression. The coexpression of these cellular genes may play a role in the altering T-cell growth following retroviral infection. PMID:3010456

Greene, W C; Leonard, W J; Wano, Y; Svetlik, P B; Peffer, N J; Sodroski, J G; Rosen, C A; Goh, W C; Haseltine, W A

1986-05-16

159

Multiple Thyrotropin ?-Subunit and Thyrotropin Receptor-Related Genes Arose during Vertebrate Evolution  

PubMed Central

Thyroid-stimulating hormone (TSH) is composed of a specific ? subunit and an ? subunit that is shared with the two pituitary gonadotropins. The three ? subunits derive from a common ancestral gene through two genome duplications (1R and 2R) that took place before the radiation of vertebrates. Analysis of genomic data from phylogenetically relevant species allowed us to identify an additional Tsh? subunit-related gene that was generated through 2R. This gene, named Tsh?2, present in cartilaginous fish, little skate and elephant shark, and in early lobe-finned fish, coelacanth and lungfish, was lost in ray-finned fish and tetrapods. The absence of a second type of TSH receptor (Tshr) gene in these species suggests that both TSHs act through the same receptor. A novel Tsh? sister gene, named Tsh?3, was generated through the third genomic duplication (3R) that occurred early in the teleost lineage. Tsh?3 is present in most teleost groups but was lostin tedraodontiforms. The 3R also generated a second Tshr, named Tshrb. Interestingly, the new Tshrb was translocated from its original chromosomic position after the emergence of eels and was then maintained in its new position. Tshrb was lost in tetraodontiforms and in ostariophysians including zebrafish although the latter species have two TSHs, suggesting that TSHRb may be dispensable. The tissue distribution of duplicated Tsh?s and Tshrs was studied in the European eel. The endocrine thyrotropic function in the eel would be essentially mediated by the classical Tsh? and Tshra, which are mainly expressed in the pituitary and thyroid, respectively. Tsh?3 and Tshrb showed a similar distribution pattern in the brain, pituitary, ovary and adipose tissue, suggesting a possible paracrine/autocrine mode of action in these non-thyroidal tissues. Further studies will be needed to determine the binding specificity of the two receptors and how these two TSH systems are interrelated. PMID:25386660

Maugars, Gersende; Dufour, Sylvie; Cohen-Tannoudji, Joëlle; Quérat, Bruno

2014-01-01

160

The dynamic nature of type 1 cannabinoid receptor (CB1) gene transcription  

PubMed Central

The type 1 cannabinoid receptor (CB1) is an integral component of the endocannabinoid system that modulates several functions in the CNS and periphery. The majority of our knowledge of the endocannabinoid system involves ligand–receptor binding, mechanisms of signal transduction, and protein–protein interactions. In contrast, comparatively little is known about regulation of CB1 gene expression. The levels and anatomical distribution of CB1 mRNA and protein are developmental stage-specific and are dysregulated in several pathological conditions. Moreover, exposure to a variety of drugs, including cannabinoids themselves, alters CB1 gene expression and mRNA levels. As such, alterations in CB1 gene expression are likely to affect the optimal response to cannabinoid-based therapies, which are being developed to treat a growing number of conditions. Here, we will examine the regulation of CB1 mRNA levels and the therapeutic potential inherent in manipulating expression of this gene. Linked Articles This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.167.issue-8 PMID:22924606

Laprairie, RB; Kelly, MEM; Denovan-Wright, EM

2012-01-01

161

Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression  

PubMed Central

We have investigated the effects of ligation of the fibronectin receptor (FnR) on gene expression in rabbit synovial fibroblasts. Monoclonal antibodies to the FnR that block initial adhesion of fibroblasts to fibronectin induced the expression of genes encoding the secreted extracellular matrix-degrading metalloproteinases collagenase and stromelysin. That induction was a direct consequence of interaction with the FnR was shown by the accumulation of mRNA for stromelysin and collagenase. Monoclonal antibodies to several other membrane glycoprotein receptors had no effect on metalloproteinase gene expression. Less than 2 h of treatment of the fibroblasts with anti-FnR in solution was sufficient to trigger the change in gene expression, and induction was blocked by dexamethasone. Unlike other inducers of metalloproteinase expression, including phorbol diesters and growth factors, addition of the anti-FnR in solution to cells adherent to serum-derived adhesion proteins or collagen produced no detectable change in cell shape or actin microfilament organization. Inductive effects were potentiated by cross-linking of the ligand. Fab fragments of anti-FnR were ineffective unless cross-linked or immobilized on the substrate. Adhesion of fibroblasts to native fibronectin did not induce metallo-proteinases. However, adhesion to covalently immobilized peptides containing the arg-gly-asp sequence that were derived from fibronectin, varying in size from hexapeptides up to 120 kD, induced collagenase and stromelysin gene expression. This suggests that degradation products of fibronectin are the natural inductive ligands for the FnR. These data demonstrate that signals leading to changes in gene expression are transduced by the FnR, a member of the integrin family of extracellular matrix receptors. The signaling of changes in gene expression by the FnR is distinct from signaling involving cell shape and actin cytoarchitecture. At least two distinct signals are generated: the binding of fibronectin-derived fragments and adhesion- blocking antibodies to the FnR triggers events different from those triggered by binding of the native fibronectin ligand. Because the genes regulated by this integrin are for enzymes that degrade the extracellular matrix, these results suggest that information transduced by the binding of various ligands to integrins may orchestrate the expression of genes regulating cell behavior in the extracellular environment. PMID:2547805

1989-01-01

162

Control of Energy Balance by Hypothalamic Gene Circuitry Involving Two Nuclear Receptors, Neuron-Derived Orphan Receptor 1 and Glucocorticoid Receptor  

PubMed Central

Nuclear receptors (NRs) regulate diverse physiological processes, including the central nervous system control of energy balance. However, the molecular mechanisms for the central actions of NRs in energy balance remain relatively poorly defined. Here we report a hypothalamic gene network involving two NRs, neuron-derived orphan receptor 1 (NOR1) and glucocorticoid receptor (GR), which directs the regulated expression of orexigenic neuropeptides agouti-related peptide (AgRP) and neuropeptide Y (NPY) in response to peripheral signals. Our results suggest that the anorexigenic signal leptin induces NOR1 expression likely via the transcription factor cyclic AMP response element-binding protein (CREB), while the orexigenic signal glucocorticoid mobilizes GR to inhibit NOR1 expression by antagonizing the action of CREB. Also, NOR1 suppresses glucocorticoid-dependent expression of AgRP and NPY. Consistently, relative to wild-type mice, NOR1-null mice showed significantly higher levels of AgRP and NPY and were less responsive to leptin in decreasing the expression of AgRP and NPY. These results identify mutual antagonism between NOR1 and GR to be a key rheostat for peripheral metabolic signals to centrally control energy balance. PMID:23897430

Kim, Sun-Gyun; Lee, Bora; Kim, Dae-Hwan; Kim, Juhee; Lee, Soo-Kyung

2013-01-01

163

Epigenetic Dysregulation of 15q11-13 GABA A Receptor Genes in Autism  

Microsoft Academic Search

\\u000a GABA is the major inhibitory neurotransmitter in the mammalian brain and defects in inhibition have been implicated in autism\\u000a spectrum disorders. GABA inhibition is mediated through a variety of receptor subunit genes. Three GABAA receptor subunit\\u000a genes, GABRB3, GABRA5, and GABRG3 are located on chromosome 15q11-13. In addition to GABAA receptor subunit genes, chromosome\\u000a 15q11-13 contains genes that are expressed

Amber Hogart; Janine M. LaSalle

164

Gene silencing to investigate the roles of receptor-like proteins in Arabidopsis  

PubMed Central

Receptor-like proteins (RLPs) are cell surface receptors that play important roles in various processes. In several plant species RLPs have been found to play a role in disease resistance, including the tomato Cf and Ve proteins and the apple HcrVf proteins that mediate resistance against the fungal pathogens Cladosporium fulvum, Verticillium spp., and Venturia inaequalis, respectively. The Arabidopsis genome contains 57 AtRLP genes. Two of these, CLV2 (AtRLP10) and TMM (AtRLP17), have well-characterized functions in meristem and stomatal development, respectively, while AtRLP52 is required for defense against powdery mildew. We recently reported the assembly of a genome-wide collection of T-DNA insertion lines for the Arabidopsis AtRLP genes. This collection was functionally analyzed with respect to plant growth, development and sensitivity to various stress responses including pathogen susceptibility. Only few new phenotypes were discovered; while AtRLP41 was found to mediate abscisic acid sensitivity, AtRLP30 (and possibly AtRLP18) was found to be required for full non-host resistance to a bacterial pathogen. Possibly, identification of novel phenotypes is obscured by functional redundancy. Therefore, RNA interference (RNAi) to target the expression of multiple AtRLP genes simultaneously was employed followed by functional analysis of the RNAi lines. PMID:19704533

Ellendorff, Ursula; Zhang, Zhao

2008-01-01

165

Variants in the vitamin D receptor gene and asthma  

PubMed Central

Background Early lifetime exposure to dietary or supplementary vitamin D has been predicted to be a risk factor for later allergy. Twin studies suggest that response to vitamin D exposure might be influenced by genetic factors. As these effects are primarily mediated through the vitamin D receptor (VDR), single base variants in this gene may be risk factors for asthma or allergy. Results 951 individuals from 224 pedigrees with at least 2 asthmatic children were analyzed for 13 SNPs in the VDR. There was no preferential transmission to children with asthma. In their unaffected sibs, however, one allele in the 5' region was 0.5-fold undertransmitted (p = 0.049), while two other alleles in the 3' terminal region were 2-fold over-transmitted (p = 0.013 and 0.018). An association was also seen with bronchial hyperreactivity against methacholine and with specific immunoglobulin E serum levels. Conclusion The transmission disequilibrium in unaffected sibs of otherwise multiple-affected families seem to be a powerful statistical test. A preferential transmission of vitamin D receptor variants to children with asthma could not be confirmed but raises the possibility of a protective effect for unaffected children. PMID:15651992

Wjst, Matthias

2005-01-01

166

Respiratory syncytial virus represses glucocorticoid receptor-mediated gene activation.  

PubMed

Respiratory syncytial virus (RSV) is a common cause of bronchiolitis in infants. Although antiinflammatory in nature, glucocorticoids have been shown to be ineffective in the treatment of RSV-induced bronchiolitis and wheezing. In addition, the effectiveness of glucocorticoids at inhibiting RSV-induced proinflammatory cytokine production in cell culture has been questioned. In this study, we have investigated the effect of RSV infection on glucocorticoid-induced gene activation in lung epithelium-derived cells. We show that RSV infection inhibits dexamethasone induction of three glucocorticoid receptor (GR)-regulated genes (glucocorticoid-inducible leucine zipper, FK506 binding protein, and MAPK phosphatase 1) in A549, BEAS-2B cells, and primary small airway epithelial cells. UV irradiation of the virus prevents this repression, suggesting that viral replication is required. RSV is known to activate the nuclear factor ?B (NF?B) pathway, which is mutually antagonistic towards the GR pathway. However, specific inhibition of NF?B had no effect on the repression of GR-induced genes by RSV infection, indicating that RSV repression of GR is independent of NF?B. RSV infection of A549 cells does not alter GR protein levels or GR nuclear translocation but does reduce GR binding to the promoters of the glucocorticoid responsive genes analyzed in this study. Repression of GR by RSV infection may account for the apparent clinical ineffectiveness of glucocorticoids in RSV bronchiolitis therapy. In addition, this data adds to our previously published data suggesting that GR may be a general target for infectious agents. Identifying the mechanisms through which this suppression occurs may lead to the development of novel therapeutics. PMID:21190962

Hinzey, Adam; Alexander, Jacob; Corry, Jacqueline; Adams, Kathleen M; Claggett, Amanda M; Traylor, Zachary P; Davis, Ian C; Webster Marketon, Jeanette I

2011-02-01

167

GABAA receptor subunit gene expression in human prefrontal cortex: comparison of schizophrenics and controls  

NASA Technical Reports Server (NTRS)

The prefrontal cortex of schizophrenics is hypoactive and displays changes related to inhibitory, GABAergic neurons, and GABAergic synapses. These changes include decreased levels of glutamic acid decarboxylase (GAD), the enzyme for GABA synthesis, upregulation of muscimol binding, and downregulation of benzodiazepine binding to GABAA receptors. Studies in the visual cortex of nonhuman primates have demonstrated that gene expression for GAD and for several GABAA receptor subunit polypeptides is under control of neuronal activity, raising the possibility that similar mechanisms in the hypoactive prefrontal cortex of schizophrenics may explain the abnormalities in GAD and in GABAA receptor regulation. In the present study, which is the first of its type on human cerebral cortex, levels of mRNAs for six GABAA receptor subunits (alpha 1, alpha 2, alpha 5, beta 1, beta 2, gamma 2) and their laminar expression patterns were analyzed in the prefrontal cortex of schizophrenics and matched controls, using in situ hybridization histochemistry and densitometry. Three types of laminar expression pattern were observed: mRNAs for the alpha 1, beta 2, and gamma 2 subunits, which are the predominant receptor subunits expressed in the mature cortex, were expressed at comparatively high levels by cells of all six cortical layers, but most intensely by cells in lower layer III and layer IV. mRNAs for the alpha 2, alpha 5, and beta 1 subunits were expressed at lower levels; alpha 2 and beta 1 were expressed predominantly by cells in layers II, III, and IV; alpha 5 was expressed predominantly in layers IV, V, and VI. There were no significant changes in overall mRNA levels for any of the receptor subunits in the prefrontal cortex of schizophrenics, and the laminar expression pattern of all six receptor subunit mRNAs did not differ between schizophrenics and controls. Because gene expression for GABAA receptor subunits is not consistently altered in the prefrontal cortex of schizophrenics, the previously reported upregulation of muscimol binding sites and downregulation of benzodiazepine binding sites in the prefrontal and adjacent cingulate cortex of schizophrenics are possibly due to posttranscriptional modifications of mRNAs and their translated polypeptides.

Akbarian, S.; Huntsman, M. M.; Kim, J. J.; Tafazzoli, A.; Potkin, S. G.; Bunney, W. E. Jr; Jones, E. G.; Bloom, F. E. (Principal Investigator)

1995-01-01

168

Progesterone receptor gene variants and risk of endometrial cancer  

PubMed Central

Prolonged excessive estrogen exposure unopposed by progesterone is widely accepted to be a risk factor for endometrial cancer development. The physiological function of progesterone is dependent upon the presence of its receptor [progesterone receptor (PGR)] and several studies have reported single nucleotide polymorphisms (SNPs) in the PGR gene to be associated with endometrial cancer risk. We sought to confirm the associations with endometrial cancer risk previously reported for four different PGR polymorphisms. A maximum of 2888 endometrial cancer cases and 4483 female control subjects from up to three studies were genotyped for four PGR polymorphisms (rs1042838, rs10895068, rs11224561 and rs471767). Logistic regression with adjustment for age, study, ethnicity and body mass index was performed to calculate odds ratios (ORs) and associated 95% confidence intervals (CIs) and P-values. Of the four SNPs investigated, only rs11224561 in the 3? region of the PGR gene was found to be significantly associated with endometrial cancer risk. The A allele of the rs11224561 SNP was associated with increased risk of endometrial cancer (OR per allele 1.31; 95% CI 1.12–1.53, P = 0.001, adjusted for age and study), an effect of the same magnitude and direction as reported previously. We have validated the endometrial cancer risk association with a tagSNP in the 3? untranslated region of PGR previously reported in an Asian population. Replication studies will be required to refine the risk estimate and to establish if this, or a correlated SNP, is the underlying causative variant. PMID:21148628

O'Mara, Tracy A.; Fahey, Paul; Ferguson, Kaltin; Marquart, Louise; Lambrechts, Diether; Despierre, Evelyn; Vergote, Ignace; Amant, Frederic; Hall, Per; Liu, Jianjun; Czene, Kamila; Rebbeck, Timothy R.; Ahmed, Shahana; Dunning, Alison M.; Gregory, Catherine S.; Shah, Mitul; Webb, Penelope M.; Spurdle, Amanda B.

2011-01-01

169

Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits  

PubMed Central

Background Low vitamin D status has been shown to be a risk factor for several metabolic traits such as obesity, diabetes and cardiovascular disease. The biological actions of 1, 25-dihydroxyvitamin D, are mediated through the vitamin D receptor (VDR), which heterodimerizes with retinoid X receptor, gamma (RXRG). Hence, we examined the potential interactions between the tagging polymorphisms in the VDR (22 tag SNPs) and RXRG (23 tag SNPs) genes on metabolic outcomes such as body mass index, waist circumference, waist-hip ratio (WHR), high- and low-density lipoprotein (LDL) cholesterols, serum triglycerides, systolic and diastolic blood pressures and glycated haemoglobin in the 1958 British Birth Cohort (1958BC, up to n?=?5,231). We used Multifactor- dimensionality reduction (MDR) program as a non-parametric test to examine for potential interactions between the VDR and RXRG gene polymorphisms in the 1958BC. We used the data from Northern Finland Birth Cohort 1966 (NFBC66, up to n?=?5,316) and Twins UK (up to n?=?3,943) to replicate our initial findings from 1958BC. Results After Bonferroni correction, the joint-likelihood ratio test suggested interactions on serum triglycerides (4 SNP - SNP pairs), LDL cholesterol (2 SNP - SNP pairs) and WHR (1 SNP - SNP pair) in the 1958BC. MDR permutation model testing analysis showed one two-way and one three-way interaction to be statistically significant on serum triglycerides in the 1958BC. In meta-analysis of results from two replication cohorts (NFBC66 and Twins UK, total n?=?8,183), none of the interactions remained after correction for multiple testing (Pinteraction >0.17). Conclusions Our results did not provide strong evidence for interactions between allelic variations in VDR and RXRG genes on metabolic outcomes; however, further replication studies on large samples are needed to confirm our findings. PMID:24641809

2014-01-01

170

Fluoxetine potentiation of methylphenidate-induced gene regulation in striatal output pathways: potential role for 5-HT1B receptor.  

PubMed

Drug combinations that include the psychostimulant methylphenidate plus a selective serotonin reuptake inhibitor (SSRI) such as fluoxetine are increasingly used in children and adolescents. For example, this combination is indicated in the treatment of attention-deficit/hyperactivity disorder and depression comorbidity and other mental disorders. Such co-exposure also occurs in patients on SSRIs who use methylphenidate as a cognitive enhancer. The neurobiological consequences of these drug combinations are poorly understood. Methylphenidate alone can produce gene regulation effects that mimic addiction-related gene regulation by cocaine, consistent with its moderate addiction liability. We have previously shown that combining SSRIs with methylphenidate potentiates methylphenidate-induced gene regulation in the striatum. The present study investigated which striatal output pathways are affected by the methylphenidate + fluoxetine combination, by assessing effects on pathway-specific neuropeptide markers, and which serotonin receptor subtypes may mediate these effects. Our results demonstrate that a 5-day repeated treatment with fluoxetine (5 mg/kg) potentiates methylphenidate (5 mg/kg)-induced expression of both dynorphin (direct pathway marker) and enkephalin (indirect pathway). These changes were accompanied by correlated increases in the expression of the 5-HT1B, but not 5-HT2C, serotonin receptor in the same striatal regions. A further study showed that the 5-HT1B receptor agonist CP94253 (3-10 mg/kg) mimics the fluoxetine potentiation of methylphenidate-induced gene regulation. These findings suggest a role for the 5-HT1B receptor in the fluoxetine effects on striatal gene regulation. Given that 5-HT1B receptors are known to facilitate addiction-related gene regulation and behavior, our results suggest that SSRIs may enhance the addiction liability of methylphenidate by increasing 5-HT1B receptor signaling. PMID:25218038

Van Waes, Vincent; Ehrlich, Sarah; Beverley, Joel A; Steiner, Heinz

2015-02-01

171

Physical mapping of the retinoid X receptor B gene in mouse and human  

SciTech Connect

Retinoid X receptors (RXRs) are zinc finger-containing nuclear transcription factors. They belong to the nuclear receptor superfamily that contains retinoid receptors, vitamin D receptors, thyroid hormone receptors, and steroid hormone receptors as well as the so-called orphan receptors. We previously mapped all three RXR genes on mouse chromosomes, using a panel of Mus spretus-Mus musculus interspecific backcross mice: namely, the RXRA-gene (Rxra) on Chr 2 near the centromere, the RXRB gene (Rxrb) on Chr 17 in the H2 region, and the RXRG gene (Rxrg) on distal Chr 1. Using cosmid clones that cover the major histocompatibility complex (MHC) region, we determined the precise physical map positions of the gene encoding mouse and human RXRB, respectively. The mouse gene (Rxrb) maps between H2-Ke4 and H2-Ke5: namely, immediately telomeric to H2-Ke4 which encodes a histidine-rich transmembrane protein, and 12 kilobases centromeric to H2-Ke5 which is expressed in lymphoid tissues, Rxrb and H2-Ke4 are transcribed into opposite directions from a CpG-rich promoter of about 250 base pairs. This gene organization is well conserved also in the human genome at the HLA-DP subregion of Chr 6p, underscoring the strong conservation of the gene organization in the MHC region between the two mammals. 54 refs., 4 figs.

Nagata, T.; Kitagawa, K.; Taketo, M. [Banyu Tsukuba Research Institute, Tsukuba (Japan); Weiss, E.H. [Ludwig-Maximilians-Univ., Munich (Germany); Abe, K. [Kumamoto Univ. School of Medicine, Kumamoto (Japan); Ando, A.; Yara-Kikuti, Y.; Inoko, H. [Tokai Univ. School of Medicine, Isehara (Japan); Seldin, M.F. [Duke Univ. Medical Center, Durham, NC (United States); Ozato, K. [National Institutes of Health, Bethesda, MD (United States)

1995-01-11

172

The complex NOD-like receptor repertoire of the coral Acropora digitifera includes novel domain combinations.  

PubMed

Innate immunity in corals is of special interest not only in the context of self-defense but also in relation to the establishment and collapse of their obligate symbiosis with dinoflagellates of the genus Symbiodinium. In innate immunity system of vertebrates, approximately 20 tripartite nucleotide oligomerization domain (NOD)-like receptor proteins that are defined by the presence of a NAIP, CIIA, HET-E and TP1 (NACHT) domain, a C-terminal leucine-rich repeat (LRR) domain, and one of three types of N-terminal effector domain, are known to function as the primary intracellular pattern recognition molecules. Surveying the coral genome revealed not only a larger number of NACHT- and related domain nucleotide-binding adaptor shared by APAF-1, R proteins, and CED-4 (NB-ARC)-encoding loci (~500) than in other metazoans but also surprising diversity of domain combinations among the coral NACHT/NB-ARC-containing proteins; N-terminal effector domains included the apoptosis-related domains caspase recruitment domain (CARD), death effector domain (DED), and Death, and C-terminal repeat domains included LRRs, tetratricopeptide repeats, ankyrin repeats, and WD40 repeats. Many of the predicted coral proteins that contain a NACHT/NB-ARC domain also contain a glycosyl transferase group 1 domain, a novel domain combination first found in metazoans. Phylogenetic analyses suggest that the NACHT/NB-ARC domain inventories of various metazoan lineages, including corals, are largely products of lineage-specific expansions. Many of the NACHT/NB-ARC loci are organized in pairs or triplets in the Acropora genome, suggesting that the large coral NACHT/NB-ARC repertoire has been generated at least in part by tandem duplication. In addition, shuffling of N-terminal effector domains may have occurred after expansions of specific NACHT/NB-ARC-repeat domain types. These results illustrate the extraordinary complexity of the innate immune repertoire of corals, which may in part reflect adaptive evolution to a symbiotic lifestyle in a uniquely complex and challenging environment. PMID:22936719

Hamada, Mayuko; Shoguchi, Eiichi; Shinzato, Chuya; Kawashima, Takeshi; Miller, David J; Satoh, Nori

2013-01-01

173

On the Origin and Evolution of Vertebrate Olfactory Receptor Genes: Comparative Genome Analysis Among 23 Chordate Species  

PubMed Central

Olfaction is a primitive sense in organisms. Both vertebrates and insects have receptors for detecting odor molecules in the environment, but the evolutionary origins of these genes are different. Among studied vertebrates, mammals have ?1,000 olfactory receptor (OR) genes, whereas teleost fishes have much smaller (?100) numbers of OR genes. To investigate the origin and evolution of vertebrate OR genes, I attempted to determine near-complete OR gene repertoires by searching whole-genome sequences of 14 nonmammalian chordates, including cephalochordates (amphioxus), urochordates (ascidian and larvacean), and vertebrates (sea lamprey, elephant shark, five teleost fishes, frog, lizard, and chicken), followed by a large-scale phylogenetic analysis in conjunction with mammalian OR genes identified from nine species. This analysis showed that the amphioxus has >30 vertebrate-type OR genes though it lacks distinctive olfactory organs, whereas all OR genes appear to have been lost in the urochordate lineage. Some groups of genes (?, ?, and ?) that are phylogenetically nested within vertebrate OR genes showed few gene gains and losses, which is in sharp contrast to the evolutionary pattern of OR genes, suggesting that they are actually non-OR genes. Moreover, the analysis demonstrated a great difference in OR gene repertoires between aquatic and terrestrial vertebrates, reflecting the necessity for the detection of water-soluble and airborne odorants, respectively. However, a minor group (?) of genes that are atypically present in both aquatic and terrestrial vertebrates was also found. These findings should provide a critical foundation for further physiological, behavioral, and evolutionary studies of olfaction in various organisms. PMID:20333175

2009-01-01

174

Multiple ramp domains are required for generation of amylin receptor phenotype from the calcitonin receptor gene product.  

PubMed

Calcitonin (CT), calcitonin gene-related peptide (CGRP), amylin, and adrenomedullin constitute a family of structurally related peptides that signal via either the calcitonin receptor-like receptor or the CT receptor, with receptor phenotype determined by coexpression of one of the three receptor activity-modifying proteins (RAMPs). The nature of the interaction between the receptor and RAMP was investigated using chimeras between RAMP1 and RAMP2 where the amino-terminal domain of RAMP1 was attached to the transmembrane domain and carboxy terminus of RAMP2 and called RAMP1/2, and vice versa for RAMP2/1. Cotransfection of wild-type or chimeric RAMPs with the insert-negative isoform of the human CT receptor (hCTR(I1-)) into COS-7 cells resulted in the expression of (125)I-rat amylin binding sites. Highest specific binding was observed when either RAMP1 or RAMP2/1 were cotransfected, indicating the importance of the RAMP transmembrane domain and/or carboxy terminus for the degree to which amylin receptors are expressed. In contrast, the phenotype generated was primarily determined by the amino terminus, with similar RAMP1- and RAMP1/2-induced receptor phenotypes that had higher affinity for human CGRPalpha and lower affinity for human calcitonin than the RAMP2- and RAMP2/1-induced receptors. PMID:10623626

Zumpe, E T; Tilakaratne, N; Fraser, N J; Christopoulos, G; Foord, S M; Sexton, P M

2000-01-01

175

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium  

PubMed Central

Background: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods: Data were combined from 49 studies, including 53?835 cases and 50?156 controls, of which 89?050 (46?450 cases and 42?600 controls) were of European ancestry, 12?893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02–1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. PMID:24548884

Agarwal, D; Pineda, S; Michailidou, K; Herranz, J; Pita, G; Moreno, L T; Alonso, M R; Dennis, J; Wang, Q; Bolla, M K; Meyer, K B; Menéndez-Rodríguez, P; Hardisson, D; Mendiola, M; González-Neira, A; Lindblom, A; Margolin, S; Swerdlow, A; Ashworth, A; Orr, N; Jones, M; Matsuo, K; Ito, H; Iwata, H; Kondo, N; Hartman, M; Hui, M; Lim, W Y; T-C Iau, P; Sawyer, E; Tomlinson, I; Kerin, M; Miller, N; Kang, D; Choi, J-Y; Park, S K; Noh, D-Y; Hopper, J L; Schmidt, D F; Makalic, E; Southey, M C; Teo, S H; Yip, C H; Sivanandan, K; Tay, W-T; Brauch, H; Brüning, T; Hamann, U; Dunning, A M; Shah, M; Andrulis, I L; Knight, J A; Glendon, G; Tchatchou, S; Schmidt, M K; Broeks, A; Rosenberg, E H; van't Veer, L J; Fasching, P A; Renner, S P; Ekici, A B; Beckmann, M W; Shen, C-Y; Hsiung, C-N; Yu, J-C; Hou, M-F; Blot, W; Cai, Q; Wu, A H; Tseng, C-C; Van Den Berg, D; Stram, D O; Cox, A; Brock, I W; Reed, M W R; Muir, K; Lophatananon, A; Stewart-Brown, S; Siriwanarangsan, P; Zheng, W; Deming-Halverson, S; Shrubsole, M J; Long, J; Shu, X-O; Lu, W; Gao, Y-T; Zhang, B; Radice, P; Peterlongo, P; Manoukian, S; Mariette, F; Sangrajrang, S; McKay, J; Couch, F J; Toland, A E; Yannoukakos, D; Fletcher, O; Johnson, N; Silva, I dos Santos; Peto, J; Marme, F; Burwinkel, B; Guénel, P; Truong, T; Sanchez, M; Mulot, C; Bojesen, S E; Nordestgaard, B G; Flyer, H; Brenner, H; Dieffenbach, A K; Arndt, V; Stegmaier, C; Mannermaa, A; Kataja, V; Kosma, V-M; Hartikainen, J M; Lambrechts, D; Yesilyurt, B T; Floris, G; Leunen, K; Chang-Claude, J; Rudolph, A; Seibold, P; Flesch-Janys, D; Wang, X; Olson, J E; Vachon, C; Purrington, K; Giles, G G; Severi, G; Baglietto, L; Haiman, C A; Henderson, B E; Schumacher, F; Le Marchand, L; Simard, J; Dumont, M; Goldberg, M S; Labrèche, F; Winqvist, R; Pylkäs, K; Jukkola-Vuorinen, A; Grip, M; Devilee, P; Tollenaar, R A E M; Seynaeve, C; García-Closas, M; Chanock, S J; Lissowska, J; Figueroa, J D; Czene, K; Eriksson, M; Humphreys, K; Darabi, H; Hooning, M J; Kriege, M; Collée, J M; Tilanus-Linthorst, M; Li, J; Jakubowska, A; Lubinski, J; Jaworska-Bieniek, K; Durda, K; Nevanlinna, H; Muranen, T A; Aittomäki, K; Blomqvist, C; Bogdanova, N; Dörk, T; Hall, P; Chenevix-Trench, G; Easton, D F; Pharoah, P D P; Arias-Perez, J I; Zamora, P; Benítez, J; Milne, R L

2014-01-01

176

A comparison of reptilian and avian olfactory receptor gene repertoires: Species-specific expansion of group ? genes in birds  

Microsoft Academic Search

BACKGROUND: The detection of odorants is mediated by olfactory receptors (ORs). ORs are G-protein coupled receptors that form a remarkably large protein superfamily in vertebrate genomes. We used data that became available through recent sequencing efforts of reptilian and avian genomes to identify the complete OR gene repertoires in a lizard, the green anole (Anolis carolinensis), and in two birds,

Silke S Steiger; Vladimir Y Kuryshev; Marcus C Stensmyr; Bart Kempenaers; Jakob C Mueller

2009-01-01

177

The evolution of drug-activated nuclear receptors: one ancestral gene diverged into two xenosensor genes in mammals  

Microsoft Academic Search

BACKGROUND: Drugs and other xenobiotics alter gene expression of cytochromes P450 (CYP) by activating the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) in mammals. In non-mammalian species, only one xenosensor gene has been found. Using chicken as a model organism, the aim of our study was to elucidate whether non-mammalian species only have one or two xenosensors like

Christoph Handschin; Sharon Blättler; Adrian Roth; Renate Looser; Mikael Oscarson; Michel R Kaufmann; Michael Podvinec; Carmela Gnerre; Urs A Meyer

2004-01-01

178

The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops  

PubMed Central

Circadian clocks synchronise biological processes with the day/night cycle, using molecular mechanisms that include interlocked, transcriptional feedback loops. Recent experiments identified the evening complex (EC) as a repressor that can be essential for gene expression rhythms in plants. Integrating the EC components in this role significantly alters our mechanistic, mathematical model of the clock gene circuit. Negative autoregulation of the EC genes constitutes the clock's evening loop, replacing the hypothetical component Y. The EC explains our earlier conjecture that the morning gene PSEUDO-RESPONSE REGULATOR 9 was repressed by an evening gene, previously identified with TIMING OF CAB EXPRESSION1 (TOC1). Our computational analysis suggests that TOC1 is a repressor of the morning genes LATE ELONGATED HYPOCOTYL and CIRCADIAN CLOCK ASSOCIATED1 rather than an activator as first conceived. This removes the necessity for the unknown component X (or TOC1mod) from previous clock models. As well as matching timeseries and phase-response data, the model provides a new conceptual framework for the plant clock that includes a three-component repressilator circuit in its complex structure. PMID:22395476

Pokhilko, Alexandra; Fernández, Aurora Piñas; Edwards, Kieron D; Southern, Megan M; Halliday, Karen J; Millar, Andrew J

2012-01-01

179

The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops.  

PubMed

Circadian clocks synchronise biological processes with the day/night cycle, using molecular mechanisms that include interlocked, transcriptional feedback loops. Recent experiments identified the evening complex (EC) as a repressor that can be essential for gene expression rhythms in plants. Integrating the EC components in this role significantly alters our mechanistic, mathematical model of the clock gene circuit. Negative autoregulation of the EC genes constitutes the clock's evening loop, replacing the hypothetical component Y. The EC explains our earlier conjecture that the morning gene Pseudo-Response Regulator 9 was repressed by an evening gene, previously identified with Timing Of CAB Expression1 (TOC1). Our computational analysis suggests that TOC1 is a repressor of the morning genes Late Elongated Hypocotyl and Circadian Clock Associated1 rather than an activator as first conceived. This removes the necessity for the unknown component X (or TOC1mod) from previous clock models. As well as matching timeseries and phase-response data, the model provides a new conceptual framework for the plant clock that includes a three-component repressilator circuit in its complex structure. PMID:22395476

Pokhilko, Alexandra; Fernández, Aurora Piñas; Edwards, Kieron D; Southern, Megan M; Halliday, Karen J; Millar, Andrew J

2012-01-01

180

Estrogen-related receptor {alpha} modulates the expression of adipogenesis-related genes during adipocyte differentiation  

SciTech Connect

Estrogen-related receptor {alpha} (ERR{alpha}) 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{alpha} in adipogenesis and white adipose tissue development has not been well studied. Here, we show that ERR{alpha} and ERR{alpha}-related transcriptional coactivators, peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) coactivator-1{alpha} (PGC-1{alpha}) and PGC-1{beta}, can be up-regulated in 3T3-L1 preadipocytes at mRNA levels under the adipogenic differentiation condition including the inducer of cAMP, glucocorticoid, and insulin. Gene knockdown by ERR{alpha}-specific siRNA results in mRNA down-regulation of fatty acid binding protein 4, PPAR{gamma}, and PGC-1{alpha} in 3T3-L1 cells in the adipogenesis medium. ERR{alpha} and PGC-1{beta} mRNA expression can be also up-regulated in another preadipocyte lineage DFAT-D1 cells and a pluripotent mesenchymal cell line C3H10T1/2 under the differentiation condition. Furthermore, stable expression of ERR{alpha} in 3T3-L1 cells up-regulates adipogenic marker genes and promotes triglyceride accumulation during 3T3-L1 differentiation. These results suggest that ERR{alpha} may play a critical role in adipocyte differentiation by modulating the expression of various adipogenesis-related genes.

Ijichi, Nobuhiro [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Ikeda, Kazuhiro [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Horie-Inoue, Kuniko [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Yagi, Ken [Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Okazaki, Yasushi [Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Inoue, Satoshi [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan) and Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan)]. E-mail: INOUE-GER@h.u-tokyo.ac.jp

2007-07-06

181

Pharmacological characterization of cyclic AMP receptors mediating gene regulation in Dictyostelium discoideum.  

PubMed

Extracellular molecules regulate gene expression in eucaryotes. Exogenous cyclic AMP (cAMP) affects the expression of a large number of developmentally regulated genes in Dictyostelium discoideum. Here, we determine the specificity of the receptor(s) which mediates gene expression by using analogs of cAMP. The order of potency with which these analogs affect the expression of specific genes is consistent with the specificity of their binding to a cell surface receptor and is distinct from their affinity for intracellular cAMP-dependent protein kinase. Dose-response curves with cAMP and adenosine 3',5'-monophosphorothioate, a nonhydrolyzable analog, revealed that the requirement for high concentrations of exogenous cAMP for regulating gene expression is due to the rapid degradation of cAMP by phosphodiesterase. The addition of low concentrations of cAMP (100 nM) or analogs in pulses also regulates gene expression. Both the genes that are positively regulated by exogenous cAMP and the discoidin gene, which is negatively regulated, respond to cAMP analogs to the same degree. Genes expressed in prespore or prestalk cells are also similarly regulated. These data suggest that the effects are mediated through the same receptor. The specificity of this receptor is indistinguishable from that of the well-characterized cell surface cAMP receptor. PMID:3023932

Haribabu, B; Dottin, R P

1986-07-01

182

Perceptual variation in umami taste and polymorphisms in TAS1R taste receptor genes1234  

PubMed Central

Background: The TAS1R1 and TAS1R3 G protein–coupled receptors are believed to function in combination as a heteromeric glutamate taste receptor in humans. Objective: We hypothesized that variations in the umami perception of glutamate would correlate with variations in the sequence of these 2 genes, if they contribute directly to umami taste. Design: In this study, we first characterized the general sensitivity to glutamate in a sample population of 242 subjects. We performed these experiments by sequencing the coding regions of the genomic TAS1R1 and TAS1R3 genes in a separate set of 87 individuals who were tested repeatedly with monopotassium glutamate (MPG) solutions. Last, we tested the role of the candidate umami taste receptor hTAS1R1-hTAS1R3 in a functional expression assay. Results: A subset of subjects displays extremes of sensitivity, and a battery of different psychophysical tests validated this observation. Statistical analysis showed that the rare T allele of single nucleotide polymorphism (SNP) R757C in TAS1R3 led to a doubling of umami ratings of 25 mmol MPG/L. Other suggestive SNPs of TAS1R3 include the A allele of A5T and the A allele of R247H, which both resulted in an approximate doubling of umami ratings of 200 mmol MPG/L. We confirmed the potential role of the human TAS1R1-TAS1R3 heteromer receptor in umami taste by recording responses, specifically to l-glutamate and inosine 5?-monophosphate (IMP) mixtures in a heterologous expression assay in HEK (human embryonic kidney) T cells. Conclusions: There is a reliable and valid variation in human umami taste of l-glutamate. Variations in perception of umami taste correlated with variations in the human TAS1R3 gene. The putative human taste receptor TAS1R1-TAS1R3 responds specifically to l-glutamate mixed with the ribonucleotide IMP. Thus, this receptor likely contributes to human umami taste perception. PMID:19587085

Chen, Qing-Ying; Alarcon, Suzanne; Tharp, Anilet; Ahmed, Osama M; Estrella, Nelsa L; Greene, Tiffani A; Rucker, Joseph; Breslin, Paul AS

2009-01-01

183

Genetic manipulation to analyze pheromone responses: knockouts of multiple receptor genes.  

PubMed

Gene targeting in the mouse is an essential technique to study gene function in vivo. Multigene families encoding vomeronasal receptor (VR) type 1 and type 2 consist of ~300 intact genes, which are clustered at multiple loci in the mouse genome. To understand the function of VRs and neurons expressing a particular VR in vivo, individual endogenous receptor genes can be manipulated by conventional gene targeting to create loss-of-function mutations or to visualize neurons and their axons expressing the VR. Multiple receptor genes in a cluster can also be deleted simultaneously by chromosome engineering, allowing analysis of function of a particular VR subfamily. Here, we describe protocols for conventional gene targeting and chromosome engineering for deleting a large genomic region in mouse embryonic stem (ES) cells. PMID:24014359

Ishii, Tomohiro

2013-01-01

184

Orphan Nuclear Receptor Nur77 Regulates Androgen Receptor Gene Expression in Mouse Ovary  

PubMed Central

The androgen receptor (AR) is a nuclear receptor that is expressed in growing follicles and involved in folliculogenesis and follicle growth. The orphan nuclear receptor, Nur77, also has an important role in steroid signaling and follicle maturation. We hypothesized that AR levels and androgen signaling through AR are regulated by Nur77 in the ovary. In the ovaries of Nur77 knockout mice (n?=?5), real-time PCR results showed that the mRNA levels of AR and an androgen signaling target gene, Kitl, were decreased by 35% and 24%, respectively, relative to wild-type mice (n?=?5), which suggested transcriptional regulation of AR by Nur77 in vivo. In cultured mouse granulosa cells and a steroidogenic human ovarian granulosa-like tumor cell line, KGN, mRNA and protein expression levels of AR were increased by overexpressing Nur77 but decreased by knocking down endogenous Nur77. Consistent with increased AR expression, chromatin immunoprecipitation showed that Nur77 bound to the NGFI-B response element (NBRE) in the AR promoter sequence. AR promoter activity was stimulated by Nur77 in HEK293T cells and attenuated in Nur77 knockout mouse granulosa cells (luciferase assay). Overexpression of Nur77 enhanced the androgenic induction of Kitl (200 nM; 48h), while knockout of Nur77 attenuated this induction. These results demonstrate that AR is regulated by Nur77 in the ovaries, and they suggest that the participation of Nur77 in androgen signaling may be essential for normal follicular development. PMID:22761936

He, Qinyuan; Jiang, Yue; Zhang, Qun; Fang, Ting; Ding, Lijun; Sun, Jianxin; Sun, Haixiang; Hu, Yali

2012-01-01

185

Retinoid X receptor and peroxisome proliferator-activated receptor-gamma agonists cooperate to inhibit matrix metalloproteinase gene expression  

Microsoft Academic Search

INTRODUCTION: We recently described the ability of retinoid X receptor (RXR) ligand LG100268 (LG268) to inhibit interleukin-1-beta (IL-1-?)-driven matrix metalloproteinase-1 (MMP-1) and MMP-13 gene expression in SW-1353 chondrosarcoma cells. Other investigators have demonstrated similar effects in chondrocytes treated with rosiglitazone, a ligand for peroxisome proliferator-activated receptor-gamma (PPAR?), for which RXR is an obligate dimerization partner. The goals of this study

Peter S Burrage; Adam C Schmucker; Yanqing Ren; Michael B Sporn; Constance E Brinckerhoff

2008-01-01

186

Allelic association of human dopamine D sub 2 receptor gene in alcoholism  

SciTech Connect

In a blinded experiment, the authors report the first allelic association of the dopamine D{sub 2} receptor gene in alcoholism. From 70 brain samples of alcoholics and nonalcoholics, DNA was digested with restriction endonucleases and probed with a clone that contained the entire 3{prime} coding exon, the polyadenylation signal, and approximately 16.4 kilobases of noncoding 3{prime} sequence of the human dopamine D{sub 2} receptor gene ({lambda}hD2G1). In the present samples, the presence of A1 allele of the dopamine D{sub 2} receptor gene correctly classified 77% of alcoholics, and its absence classified 72% of nonalcoholics. The polymorphic pattern of this receptor gene suggests that a gene that confers susceptibility to at least one form of alcoholism is located on the q22-q23 region of chromosome 11.

Blum, K.; Sheridan, P.J.; Montgomery, A.; Jagadeeswaran, P.; Nogami, H.; Briggs, A.H. (Univ. of Texas Health Science Center, San Antonio (USA)); Noble, E.P.; Ritchie, T.; Cohn, J.B. (Univ. of California, Los Angeles (USA))

1990-04-18

187

Estrogen Receptor a Gene Polymorphisms and Bone Mineral Density in Healthy Children and Young Adults  

Microsoft Academic Search

The accretion of peak bone mass is largely under genetic control, and one of the potential candidate genes is the estrogen receptor a (ERa) gene. The association of ERa gene polymorphisms with bone mineral density (BMD) was investigated in a group of 147 healthy caucasian children, adolescents, and young adults (57 boys and 90 girls) in a cross-sectional and longitudinal

A. M. Boot; I. M. van der Sluis; S. M. P. F. de Muinck Keizer-Schrama; J. B. J. van Meurs; E. P. Krenning; H. A. P. Pols; A. G. Uitterlinden

2004-01-01

188

Molecular evolution of the genes encoding receptor tyrosine kinase with immunoglobulinlike domains  

Microsoft Academic Search

Receptor tyrosine kinases (RTK) with five, three, or seven immunoglobulinlike domains in their extracellular regions are classified as subclasses III, IV, and V, respectively. Conservation of the exon\\/intron structure of the downstream part of the human KIT, FMS, and FLT3 genes that encode RTK of subclass III together with the particular chromosomal localization of these genes suggests that RTKIII genes

Dominique Rousset; François Agnès; Philippe Lachaume; Catherine André; Francis Galibert

1995-01-01

189

RESEARCH ARTICLE Open Access Inventory of the cichlid olfactory receptor gene  

E-print Network

RESEARCH ARTICLE Open Access Inventory of the cichlid olfactory receptor gene repertoires: identification of olfactory genes with more than one coding exon Naoual Azzouzi , Frederique Barloy contained large numbers of complete genes (O. niloticus 158; H. burtoni 90; M. zebra 102; N. brichardi 69; P

Boyer, Edmond

190

Roles of retinoic acid-inducible gene-I-like receptors (RLRs), Toll-like receptor (TLR) 3 and 2'-5' oligoadenylate synthetase as viral recognition receptors on human mast cells in response to viral infection.  

PubMed

To investigate the anti-viral responses of human mast cells, we performed PCR array analysis of these cells after infection with vesicular stomatitis virus (VSV). PCR array analysis revealed that human mast cells up-regulated several anti-viral genes, including melanoma differentiation-associated gene 5, retinoic acid-inducible gene-I, and Toll-like receptor 3, together with type I interferons and chemokines, upon VSV infection. Additionally, we found that 2'-5' oligoadenylate synthetase, which also works as a virus recognition receptor by activating the latent form of RNase L, leading to viral RNA degradation, was up-regulated in human mast cells upon VSV infection. Moreover, small interfering RNA analysis to identify the receptors responsible for mast cell activation by VSV revealed that these receptors reciprocally cooperate to produce anti-viral cytokines and chemokines, inhibiting VSV replication. Our findings suggest that human mast cells produce cytokines and chemokines using several viral recognition receptors, leading to the inhibition of viral replication. These data provide novel information that improves our understanding of the roles of human mast cells in immune responses against viruses. PMID:25550087

Tsutsui-Takeuchi, Mizuho; Ushio, Hiroko; Fukuda, Minoru; Yamada, Takahiko; Niyonsaba, François; Okumura, Ko; Ogawa, Hideoki; Ikeda, Shigaku

2015-03-01

191

Positive association between a DNA sequence variant in the serotonin 2A receptor gene and schizophrenia  

SciTech Connect

Sixty-two patients with schizophrenia and 96 normal controls were investigated for genetic association with restriction fragment length polymorphisms (RFLPs) in the serotonin receptor genes. A positive association between the serotonin 2A receptor gene (HTR2A) and schizophrenia was found, but not between schizophrenia and the serotonin 1A receptor gene. The positive association we report here would suggest that the DNA region with susceptibility to schizophrenia lies in the HTR2A on the long arm of chromosome 13. 15 refs., 2 tabs.

Inayama, Y.; Yoneda, H.; Sakai, T. [Osaka Medical College (Japan)] [and others] [Osaka Medical College (Japan); and others

1996-02-16

192

Receptor-dependent transcriptional activation of cytochrome P4503A genes: induction mechanisms, species differences and interindividual variation in man.  

PubMed

1. The importance of CYP3A enzymes in drug metabolism and toxicology has yielded a wealth of information on the structure, function and regulation of this subfamily and recent research emphasis has been placed on the human forms, namely CYP3A4, CYP3A5, CYP3A7 and CYP3A43. 2. The current review will focus on the receptor-dependency of CYP3A regulation and includes consideration of the regulatory roles of the glucocorticoid (GR), pregnane X (PXR) and constitutive androstane (CAR) receptors. 3. Emphasis has been placed on the topics of expression and substrate specificity, assessment of induction, species differences in induction, CYP3A promoter sequences and regulation of gene expression, structural and functional aspects of receptor-mediated, CYP3A gene activation, receptor variants and interindividual variation in human CYP3A expression, the latter encompassing environmental, physiological and genetic aspects. 4. An outline of future research needs will be discussed in the context of receptor-mediated molecular mechanisms of CYP3A gene regulation and the impact on interindividual variations in CYP3A expression. 5. Taken collectively, this review highlights the importance of understanding the molecular mechanisms of CYP3A induction as a means of rationalizing human responses to many clinically used drugs, in addition to providing a mechanistically coherent platform to understand and predict interindividual variations in response and drug-drug interactions. PMID:11958559

Gibson, G G; Plant, N J; Swales, K E; Ayrton, A; El-Sankary, W

2002-03-01

193

Vitamin D Receptor Controls Expression of the Anti-aging Klotho Gene in Mouse and Human Renal Cells  

PubMed Central

Isoforms of the mammalian klotho protein serve as membrane co-receptors that regulate renal phosphate and calcium reabsorption. Phosphaturic effects of klotho are mediated in cooperation with fibroblast growth factor receptor-1 and its FGF23 ligand. The vitamin D receptor and its 1,25-dihydroxyvitamin D3 ligand are also crucial for calcium and phosphate regulation at the kidney and participate in a feedback loop with FGF23 signaling. Herein we characterize vitamin D receptor-mediated regulation of klotho mRNA expression, including the identification of vitamin D responsive elements (VDREs) in the vicinity of both the mouse and human klotho genes. In keeping with other recent studies of vitamin D-regulated genes, multiple VDREs control klotho expression, with the most active elements located at some distance (?31 kb to ?46 kb) from the klotho transcriptional start site. We therefore postulate that the mammalian klotho gene is up-regulated by liganded VDR via multiple remote VDREs. The phosphatemic actions of 1,25-dihydroxyvitamin D3 are thus opposed via the combined phosphaturic effects of FGF23 and klotho, both of which are upregulated by the liganded vitamin D receptor. PMID:21982773

Forster, Ryan E.; Jurutka, Peter W.; Hsieh, Jui-Cheng; Haussler, Carol A.; Lowmiller, Christine L.; Kaneko, Ichiro; Haussler, Mark R.; Whitfield, G. Kerr

2011-01-01

194

A novel human gene encoding a G-protein-coupled receptor (GPR15) is located on chromosome 3  

SciTech Connect

We used sequence similarities among G-protein-coupled receptor genes to discover a novel receptor gene. Using primers based on conserved regions of the opioid-related receptors, we isolated a PCR product that was used to locate the full-length coding region of a novel human receptor gene, which we have named GPR15. A comparison of the amino acid sequence of the receptor gene, which we have named GPR15. A comparison of the amino acid sequence of the receptor encoded by GPR15 with other receptors revealed that it shared sequence identity with the angiotensin II AT1 and AT2 receptors, the interleukin 8b receptor, and the orphan receptors GPR1 and AGTL1. GPR15 was mapped to human chromosome 3q11.2-q13.1. 12 refs., 2 figs.

Heiber, M.; Marchese, A.; O`Dowd, B.F. [Univ. of Toronto, Ontario (Canada)] [and others] [Univ. of Toronto, Ontario (Canada); and others

1996-03-05

195

REST mediates androgen receptor actions on gene repression and predicts early recurrence of prostate cancer  

PubMed Central

The androgen receptor (AR) is a key regulator of prostate tumorgenesis through actions that are not fully understood. We identified the repressor element (RE)-1 silencing transcription factor (REST) as a mediator of AR actions on gene repression. Chromatin immunoprecipitation showed that AR binds chromatin regions containing well-characterized cis-elements known to mediate REST transcriptional repression, while cell imaging studies confirmed that REST and AR closely co-localize in vivo. Androgen-induced gene repression also involves modulation of REST protein turnover through actions on the ubiquitin ligase ?-TRCP. Androgen deprivation or AR blockage with inhibitor MDV3100 (Enzalutamide) leads to neuroendocrine (NE) differentiation, a phenomenon that is mimicked by REST inactivation. Gene expression profiling revealed that REST not only acts to repress neuronal genes but also genes involved in cell cycle progression, including Aurora Kinase A, that has previously been implicated in the growth of NE-like castration-resistant tumors. The analysis of prostate cancer tissue microarrays revealed that tumors with reduced expression of REST have higher probability of early recurrence, independently of their Gleason score. The demonstration that REST modulates AR actions in prostate epithelia and that REST expression is negatively correlated with disease recurrence after prostatectomy, invite a deeper characterization of its role in prostate carcinogenesis. PMID:24163104

Svensson, Charlotte; Ceder, Jens; Iglesias-Gato, Diego; Chuan, Yin-Choy; Pang, See Tong; Bjartell, Anders; Martinez, Roxana Merino; Bott, Laura; Helczynski, Leszek; Ulmert, David; Wang, Yuzhuo; Niu, Yuanjie; Collins, Colin; Flores-Morales, Amilcar

2014-01-01

196

Epigenetic regulation of olfactory receptor gene expression by the Myb–MuvB/dREAM complex  

PubMed Central

In both mammals and insects, an olfactory neuron will usually select a single olfactory receptor and repress remaining members of large receptor families. Here we show that a conserved multiprotein complex, Myb–MuvB (MMB)/dREAM, plays an important role in mediating neuron-specific expression of the carbon dioxide (CO2) receptor genes (Gr63a/Gr21a) in Drosophila. Activity of Myb in the complex is required for expression of Gr63a/Gr21a and acts in opposition to the histone methyltransferase Su(var)3-9. Consistent with this, we observed repressive dimethylated H3K9 modifications at the receptor gene loci, suggesting a mechanism for silencing receptor gene expression. Conversely, other complex members, Mip120 (Myb-interacting protein 120) and E2F2, are required for repression of Gr63a in inappropriate neurons. Misexpression in mutants is accompanied by an increase in the H3K4me3 mark of active chromatin at the receptor gene locus. Nuclei of CO2 receptor-expressing neurons contain reduced levels of the repressive subunit Mip120 compared with surrounding neurons and increased levels of Myb, suggesting that activity of the complex can be regulated in a cell-specific manner. Our evidence suggests a model in which olfactory receptors are regulated epigenetically and the MMB/dREAM complex plays a critical role in specifying, maintaining, and modulating the receptor-to-neuron map. PMID:23105004

Sim, Choon Kiat; Perry, Sarah; Tharadra, Sana Khalid; Lipsick, Joseph S.; Ray, Anandasankar

2012-01-01

197

Association of adenosine receptor gene polymorphisms and in vivo adenosine A1 receptor binding in the human brain.  

PubMed

Adenosine A1 receptors (A1ARs) and the interacting adenosine A2A receptors are implicated in neurological and psychiatric disorders. Variants within the corresponding genes ADORA1 and ADORA2A were shown associated with pathophysiologic alterations, particularly increased anxiety. It is unknown so far, if these variants might modulate the A1AR distribution and availability in different brain regions. In this pilot study, the influence of ADORA1 and ADORA2A variants on in vivo A1AR binding was assessed with the A1AR-selective positron emission tomography (PET) radioligand [(18)F]CPFPX in brains of healthy humans. Twenty-eight normal control subjects underwent PET procedures to calculate the binding potential BPND of [(18)F]CPFPX in cerebral regions and to assess ADORA1 and ADORA2A single nucleotide polymorphism (SNP) effects on regional BPND data. Our results revealed SNPs of both genes associated with [(18)F]CPFPX binding to the A1AR. The strongest effects that withstood even Bonferroni correction of multiple SNP testing were found in non-smoking subjects (N=22) for ADORA2A SNPs rs2236624 and rs5751876 (corr. Pall<0.05). SNP alleles previously identified at risk for increased anxiety like the rs5751876 T-allele corresponded to consistently higher A1AR availability in all brain regions. Our data indicate for the first time that variation of A1AR availability was associated with ADORA SNPs. The finding of increased A1AR availability in regions of the fear network, particularly in ADORA2A risk allele carriers, strongly warrants evaluation and replication in further studies including individuals with increased anxiety. PMID:24943643

Hohoff, Christa; Garibotto, Valentina; Elmenhorst, David; Baffa, Anna; Kroll, Tina; Hoffmann, Alana; Schwarte, Kathrin; Zhang, Weiqi; Arolt, Volker; Deckert, Jürgen; Bauer, Andreas

2014-12-01

198

Ancient divergence of animal protein tyrosine kinase genes demonstrated by a gene family tree including choanoflagellate genes  

Microsoft Academic Search

Animal-specific gene families involved in cell–cell communication and developmental control comprise many subfamilies with distinct domain structures and functions. They diverged by subfamily-generating duplications and domain shufflings before the parazoan–eumetazoan split. Here, we have cloned 40 PTK cDNAs from choanoflagellates, Monosiga ovata, Stephanoeca diplocostata and Codosiga gracilis, the closest relatives to animals. A phylogeny-based analysis of PTKs revealed that 40

Hiroshi Suga; Go Sasaki; Kei-ichi Kuma; Hiromi Nishiyori; Nozomi Hirose; Zhi-Hui Su; Naoyuki Iwabe; Takashi Miyata

2008-01-01

199

Functional characterization of the mouse melanocortin 3 receptor gene promoter.  

PubMed

Melanocortin receptor 3 (MC3R) is expressed in the hypothalamus and pituitary in humans and rodents, and is involved in the control of feeding, energy metabolism, and pituitary function. In the mouse pituitary, MC3R is detected in mammotrophs. This study aimed to clarify the regulatory mechanism for Mc3r expression in the mouse pituitary. The promoter activities of reporter constructs for the MC3R gene 5'-flanking region up to -4000bp (transcription initiation site designated as +1) were analyzed. The promoter activity significantly increased in the -86/+109 construct, but decreased in the -38/+109 construct, indicating that the minimal promoter required for basal expression of Mc3r is located in the -86/+109 region. Putative binding sites for transcription factors AP-1 and ATF4 were found in the 5'-flanking region of Mc3r. Site-directed mutation or deletion of these sites affected the promoter activities. In gel-shift assays with a nuclear extract of mouse anterior pituitary cells, band-shifts were detected for both sites after the addition of the nuclear extract, and were decreased in the presence of excess unlabeled probe competitors. These results indicated that both sites were involved in the regulation of Mc3r expression in anterior pituitary cells. Estradiol-17? treatment increased the Mc3r promoter activity, indicating that the gene is regulated by estradiol-17?. In conclusion, we have demonstrated the minimum promoter region required for Mc3r expression, and identified two binding sites for AP-1 and ATF4 and in the 5' upstream-flanking region of Mc3r that are essential for Mc3r expression. PMID:25701401

Okutsu, Keisuke; Ojima, Fumiya; Shinohara, Naoto; Taniuchi, Shusuke; Mizote, Yasusyo; Aoki, Kenji; Kudo, Toshiyuki; Ogoshi, Maho; Takeuchi, Sakae; Takahashi, Sumio

2015-05-10

200

[Novel therapy for malignant lymphoma: adoptive immuno-gene therapy using chimeric antigen receptor(CAR)-expressing T lymphocytes].  

PubMed

Adoptive T-cell therapy using chimeric antigen receptor (CAR) technology is a novel approach to cancer immuno-gene therapy. CARs are hybrid proteins consisting of target-antigen-specific single-chain antibody fragment fused to intracellular T-cell activation domains (CD28 or CD137/CD3 zeta receptor). CAR-expressing engineered T lymphocytes can directly recognize and kill tumor cells in an HLA independent manner. In the United States, promising results have been obtained in the clinical trials of adoptive immuno-gene therapy using CD19-CAR-T lymphocytes for the treatment of refractory B-cell malignancies, including chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL). In this review article, CD19-CAR-T gene therapy for refractory B-cell non-Hodgkin lymphoma is discussed. PMID:24724418

Ozawa, Keiya

2014-03-01

201

Thyroid hormone receptor mediates human MDR1 gene expression—Identification of the response region essential for gene expression  

Microsoft Academic Search

P-glycoprotein, encoded by the MDR1 gene, is a drug efflux transporter that is expressed in various tissues and plays an important role in the absorption and elimination of many drugs and xenobiotics. Induction of the MDR1 gene affects drug disposition and the efficacy of drug treatment. In this study, we demonstrated that the thyroid hormone receptor (TR) induces MDR1 gene

Kouichi Kurose; Mayumi Saeki; Masahiro Tohkin; Ryuichi Hasegawa

2008-01-01

202

Association study of dopamine D3 receptor gene and schizophrenia  

SciTech Connect

Several groups have reported an association between schizophrenia and the MscI polymorphism in the first exon of the dopamine D3 receptor gene (DRD3). We studied this polymorphism using a North American sample (117 patients plus 188 controls) and an Italian sample (97 patients plus 64 controls). In the first part of the study, we compared allele frequencies of schizophrenia patients and unmatched controls and observed a significant difference in the total sample (P = 0.01). The second part of the study involved a case control approach in which each schizophrenia patient was matched to a control of the same sex, and of similar age and ethnic background. The DRD3 allele frequencies of patients and controls revealed no significant difference between the two groups in the Italian (N = 53) or the North American (N = 54) matched populations; however, when these two matched samples were combined, a significant difference was observed (P = 0.026). Our results suggest that the MscI polymorphism may be associated with schizophrenia in the populations studied. 32 refs., 2 tabs.

Kennedy, J.L.; Billett, E.A.; Macciardi, F.M. [Univ. of Toronto, Ontario (Canada)] [and others

1995-12-18

203

A network of heterochronic genes including Imp1 regulates temporal changes in stem cell properties  

PubMed Central

Stem cell properties change over time to match the changing growth and regeneration demands of tissues. We showed previously that adult forebrain stem cell function declines during aging because of increased expression of let-7 microRNAs, evolutionarily conserved heterochronic genes that reduce HMGA2 expression. Here we asked whether let-7 targets also regulate changes between fetal and adult stem cells. We found a second let-7 target, the RNA binding protein IMP1, that is expressed by fetal, but not adult, neural stem cells. IMP1 expression was promoted by Wnt signaling and Lin28a expression and opposed by let-7 microRNAs. Imp1-deficient neural stem cells were prematurely depleted in the dorsal telencephalon due to accelerated differentiation, impairing pallial expansion. IMP1 post-transcriptionally inhibited the expression of differentiation-associated genes while promoting the expression of self-renewal genes, including Hmga2. A network of heterochronic gene products including Lin28a, let-7, IMP1, and HMGA2 thus regulates temporal changes in stem cell properties. DOI: http://dx.doi.org/10.7554/eLife.00924.001 PMID:24192035

Nishino, Jinsuke; Kim, Sunjung; Zhu, Yuan; Zhu, Hao; Morrison, Sean J

2013-01-01

204

Characterisation of androgen receptor function in the male reproductive system through conditional gene targeting   

E-print Network

Androgen receptor (AR) signalling is essential for the development and function of the male reproductive system. Conditional gene ablation using the Cre-loxP system has previously assisted in the elucidation of the role ...

O'Hara, Laura

2011-07-05

205

Establishing and maintaining gene expression patterns: insights from sensory receptor patterning  

PubMed Central

In visual and olfactory sensory systems with high discriminatory power, each sensory neuron typically expresses one, or very few, sensory receptor genes, excluding all others. Recent studies have provided insights into the mechanisms that generate and maintain sensory receptor expression patterns. Here, we review how this is achieved in the fly retina and compare it with the mechanisms controlling sensory receptor expression patterns in the mouse retina and in the mouse and fly olfactory systems. PMID:23293281

Rister, Jens; Desplan, Claude; Vasiliauskas, Daniel

2013-01-01

206

Expression of human platelet-activating factor receptor gene in EoL-1 cells following butyrate-induced differentiation.  

PubMed Central

Platelet-activating factor (PAF) is a potent lipid mediator of allergic inflammation through its interaction with eosinophils. Expression of the PAF receptor is modulated by many agents, including those responsible for cell differentiation. We report here that differentiation of a human eosinophilic leukaemia cell line, EoL-1, by sodium n-butyrate is associated with induction of PAF receptor gene expression, as indicated by: PAF receptor mRNA accumulation; increases in the binding of [3H]WEB 2086, a PAF antagonist; analysis of cell-surface expression of PAF receptor protein using a monoclonal anti-(PAF receptor) antibody; and augmentation of PAF-induced increase in the intracellular concentration of calcium. Using cDNA cloning, the receptor expressed in EoL-1 cells was identified as 'Transcript 1', one of two transcripts which was previously reported from human genomic analysis (Mutoh, Bito, Minami, Nakamura, Honda, Izumi, Nakata, Kurachi, Terano and Shimizu (1993) FEBS Lett. 322, 129-134). The PAF-induced calcium response and phosphoinositide turnover were decreased by pertussis toxin (PTX) treatment, suggesting that these signals are coupled largely with PTX-sensitive G-protein(s) in EoL-1 cells. These systems may provide a useful experimental model with which to investigate the relationship between eosinophilic differentiation and PAF receptor induction, and the role of eosinophils in allergic responses. Images Figure 2 Figure 4 PMID:7848283

Izumi, T; Kishimoto, S; Takano, T; Nakamura, M; Miyabe, Y; Nakata, M; Sakanaka, C; Shimizu, T

1995-01-01

207

Effects of Long-Term Antipsychotic Treatment on NMDA Receptor Binding and Gene Expression of Subunits  

Microsoft Academic Search

Postmortem studies in schizophrenic patients revealed alterations in NMDA receptor binding and gene expression of specific subunits. Because most of the patients had been treated with antipsychotics over long periods, medication effects might have influenced those findings. We treated animals with haloperidol and clozapine in clinical doses to investigate the effects of long-term antipsychotic treatment on NMDA receptor binding and

Andrea Schmitt; Mathias Zink; Bettina Müller; Brigitte May; Anne Herb; Alexander Jatzko; Dieter F. Braus; Fritz A. Henn

2003-01-01

208

Duplication of the Rdl GABA receptor subunit gene in an insecticide-resistant aphid, Myzus persicae  

Microsoft Academic Search

Resistance to cyclodiene insecticides is associated with replacements of a single amino acid (alanine 302) in a ?-aminobutyric acid (GABA) receptor subunit encoded by the single-copy gene Resistance to dieldrin (Rdl). Alanine 302 is predicted to reside within the second membrane-spanning region of the Rdl receptor, a region that is thought to line the integral chloride ion channel pore. In

N. Anthony; T. Unruh; D. Ganser; R. ffrench-Constant

1998-01-01

209

The c-erb-A gene encodes a thyroid hormone receptor  

Microsoft Academic Search

The cDNA sequence of human c-erb-A, the cellular counterpart of the viral oncogene v-erb-A, indicates that the protein encoded by the gene is related to the steroid hormone receptors. Binding studies with the protein show it to be a receptor for thyroid hormones.

Cary Weinberger; Catherine C. Thompson; Estelita S. Ong; Roger Lebo; Donald J. Gruol; Ronald M. Evans

1986-01-01

210

Regulation of adipocyte gene expression and differentiation by peroxisome proliferator activated receptor ?  

Microsoft Academic Search

Peroxisome proliferator activated receptor (PPAR) ? is an orphan member of the nuclear hormone receptor superfamily and is expressed at high levels specifically in adipose tissue. Recent data suggest that this factor is a central regulator of adipocyte gene expression and differentiation. Fibroblastic cell lines that express PPAR? ectopically can be induced to differentiate into fat cells by a variety

Peter Tontonoz; Erding Hu; Bruce M Spiegelman

1995-01-01

211

Suppression of androgen receptor-mediated gene expression by a sequence-specific  

E-print Network

Suppression of androgen receptor-mediated gene expression by a sequence-specific DNA for review April 16, 2007) Androgen receptor (AR) is essential for the growth and progression of prostate cancer in both hormone-sensitive and hormone-refrac- tory disease. A DNA-binding polyamide that targets

Dervan, Peter B.

212

The human interleukin-11 receptor {alpha} gene (IL11RA): Genomic organization and chromosome mapping  

SciTech Connect

This article discusses the organization of the human interleukin-11 receptor {alpha} gene and its localization to human chromosome 9p13 using in situ hybridization. The genetic evolution of this hematopoietic family of cytokine receptors is theorized. 29 refs., 3 figs., 1 tab.

Cherel, M.; Sorel, M.; Apiou, F. [Institut de Biologie, Nantes (France)] [and others] [Institut de Biologie, Nantes (France); and others

1996-02-15

213

Gender, variation in opioid receptor genes and sensitivity to experimental pain  

PubMed Central

Background Pain tolerance is subject to considerable inter-individual variation, which may be influenced by a number of genetic and non-genetic factors. The mu, delta and kappa opioid receptors play a role in pain perception and are thought to mediate different pain modalities. The aim of this study was to explore associations between pain thresholds and gender and genetic variants in the three opioid receptor genes (OPRM, OPRD and OPRK). Experimental multi-modal pain data from previously published studies carried out in healthy Caucasian volunteers were used in order to limit the number of confounders to the study outcome. Data on thermal skin pain (n=36), muscle pressure pain (n=31) and mechanical visceral pain (n=50)) tolerance thresholds were included. Results Nineteen genetic polymorphisms were included in linear regression modeling. Males were found to tolerate higher thermal and muscle pressure pain than females (p=0.003 and 0.02). Thirty four percent of variability in thermal skin pain was accounted for by a model consisting of OPRK rs6473799 and gender. This finding was just outside significance when correction for multiple testing was applied. Variability in muscle pressure pain tolerance was associated with OPRK rs7016778 and rs7824175. These SNPs accounted for 43% of variability in muscle pressure pain sensitivity and these findings remained significant after adjustment for multiple testing. No association was found with mechanical visceral pain. Conclusion This is a preliminary and hypothesis generating study due to the relatively small study size. However, significant association between the opioid receptor genes and experimental pain sensitivity supports the influence of genetic variability in pain perception. These findings may be used to generate hypotheses for testing in larger clinical trials of patients with painful conditions. PMID:23570317

2013-01-01

214

Basic fibroblast growth factor enhances nerve growth factor receptor gene promoter activity in human neuroblastoma cell line CHP100.  

PubMed Central

The human neuroblastoma cell line CHP100 provides a useful model system in which to study the molecular mechanisms of transcriptional regulation of the low-affinity nerve growth factor receptor (NGFR) gene during neuronal development. Basic fibroblast growth factor (bFGF) induced morphological changes in CHP100 cells, including flattening of cell bodies and neurite outgrowth. bFGF also increased p75NGFR immunoreactivity, as assessed by immunocytochemistry, and increased p75NGFR mRNA levels, as assessed by Northern (RNA) blot analysis. A chimeric gene consisting of 6.7 kb of the 5'-flanking region of the human NGFR gene linked to the chloramphenicol acetyltransferase gene was constructed. In stable transformants of CHP100 cells, 10 ng of bFGF per ml induced an eightfold increase in chloramphenicol acetyltransferase activity. These results indicate that upstream elements of the NGFR gene mediate transcriptional regulation by bFGF. Images PMID:1314950

Taiji, M; Taiji, K; Deyerle, K L; Bothwell, M

1992-01-01

215

Angiotensin II Type 1 Receptor Gene Polymorphisms in Human Essential Hypertension  

Microsoft Academic Search

Abstract We conducted ,the present study to determine whether the angiotensin II type I receptor (AT,) gene might beimplicated,in human ,essential hypertension ,by using case-control and ,linkage studies. The entire coding ,and 3' untranslated regions of the AT, receptor gene (2.2 kb) were amplified by polymerase ,chain reaction and ,submitted ,to single-strand conformation ,polymorphism ,in 60 hypertensive

Alain Bonnardeaux; Eleanor Davies; Xavier Jeunemaitre; Isabelle Fery; Anne Charru; Eric Clauser; Laurence Tiret; Francois Cambien; Pierre Corvol; Florent Soubrier

216

Comparative neuroendocrinology of steroid receptor gene expression and regulation: Relationship to physiology and behavior  

Microsoft Academic Search

Great diversity exists among vertebrates in reproductive behaviors and the neuroendocrine mechanisms underlying these behaviors. Comparisons of species with different hormone-brain-behavior relationships reveal three factors which may explain species differences in endocrine physiology and behavior: (a) sensitivity to sex steroid hormones, (b) hormone-dependent regulation of sex steroid hormone receptor gene expression, and (c) neuroanatomical distribution of steroid receptor gene expression,

Larry James Young; David Crews

1995-01-01

217

Estrogen Receptor 1 Gene Expression and Its Combination with Estrogen Receptor 2 or Aromatase Expression Predicts Survival in Non-Small Cell Lung Cancer  

PubMed Central

The biological roles of estrogen receptor 1 (ERS1), estrogen receptor 2 (ERS2), and aromatase (CYP19A1) genes in the development of non-small cell lung cancer (NSCLC) is unclear, as is the use of their expression as a prognostic factor. The aim of this study was to investigate the prognostic value of estrogen receptors and aromatase mRNA expression, along with aromatase protein concentration, in resected NSCLC patients. Tumor and non-tumor lung tissue samples were analyzed for the mRNA expression of ERS1, ERS2 and CYP19A1 by RT-PCR. Aromatase concentration was measured with an ELISA. A total of 96 patients were included. ERS1 expression was significantly higher in non-tumor tissue than in tumor samples. Two gene expression categories were created for each gene (and protein): high and low. ERS1 high category showed increased overall survival (OS) when compared to the low expression category. Aromatase protein concentration was significantly higher in tumor samples. Higher ERS1 expression in tumor tissues was related to longer overall survival. The analysis of gene expression combinations provides evidence for longer OS when both ERS1 and ERS2 are highly expressed. ESR1, alone or in combination with ERS2 or CYP19A1, is the most determining prognostic factor within the analyzed 3 genes. It seems that ERS1 can play a role in NSCLC prognosis, alone or in combination with other genes such as ERS2 or Cyp19a1. ERS2 in combination with aromatase concentration could have a similar function. PMID:25310221

Aresti, Unai; Carrera, Sergio; Iruarrizaga, Eluska; Fuente, Natalia; Marrodan, Ines; de Lobera, Abigail Ruiz; Muñoz, Alberto; Buque, Aitziber; Condori, Elizabeth; Ugalde, Irene; Calvo, Begoña; Vivanco, Guillermo López

2014-01-01

218

Detection of Clonal T-Cell Receptor ? Gene Rearrangements in Early Mycosis Fungoides\\/Sezary Syndrome by Polymerase Chain Reaction and Denaturing Gradient Gel Electrophoresis (PCR\\/DGGE)  

Microsoft Academic Search

We used a gene amplification strategy to analyze T-cell receptor (TCR) gene rearrangements in 185 specimens, including mycosis fungoides\\/Sezary syndrome (MF\\/SS), other cutaneous neoplasms, inflammatory dermatoses, reactive lymphoid tissues,and normal skin. Genomic DNA was extracted from lesional tissues and rearrangements of the TCR-? chain gene were amplified using the polymerase chain reaction (PCR) with primers specific for rearrangements involving V?1-8

Gary S. Wood; Rosnn M. Tung; Andreas C. Heaffner; Carol F. Crooks; Shaoyi Liao; Rachaci Orozco; Hendrik Veelken; Marshall E. Kadin; Howard Koh; Peter Heald; Raymond L. Barnhill; Jeffrey Sklar

1994-01-01

219

Computational Characterization of Modes of Transcriptional Regulation of Nuclear Receptor Genes  

PubMed Central

Background Nuclear receptors are a large structural class of transcription factors that act with their co-regulators and repressors to maintain a variety of biological and physiological processes such as metabolism, development and reproduction. They are activated through the binding of small ligands, which can be replaced by drug molecules, making nuclear receptors promising drug targets. Transcriptional regulation of the genes that encode them is central to gaining a deeper understanding of the diversity of their biochemical and biophysical roles and their role in disease and therapy. Even though they share evolutionary history, nuclear receptor genes have fundamentally different expression patterns, ranging from ubiquitously expressed to tissue-specific and spatiotemporally complex. However, current understanding of regulation in nuclear receptor gene family is still nascent. Methodology/Principal Findings In this study, we investigate the relationship between long-range regulation of nuclear receptor family and their known functionality. Towards this goal, we identify the nuclear receptor genes that are potential targets based on counts of highly conserved non-coding elements. We validate our results using publicly available expression (RNA-seq) and histone modification (ChIP-seq) data from the ENCODE project. We find that nuclear receptor genes involved in developmental roles show strong evidence of long-range mechanism of transcription regulation with distinct cis-regulatory content they feature clusters of highly conserved non-coding elements distributed in regions spanning several Megabases, long and multiple CpG islands, bivalent promoter marks and statistically significant higher enrichment of enhancer mark around their gene loci. On the other hand nuclear receptor genes that are involved in tissue-specific roles lack these features, having simple transcriptional controls and a greater variety of mechanisms for producing paralogs. We further examine the combinatorial patterns of histone maps associated with dynamic functional elements in order to explore the regulatory landscape of the gene family. The results show that our proposed classification capturing long-range regulation is strongly indicative of the functional roles of the nuclear receptors compared to existing classifications. Conclusions/Significanc We present a new classification for nuclear receptor gene family capturing whether a nuclear receptor is a possible target of long-range regulation or not. We compare our classification to existing structural (mechanism of action) and homology-based classifications. Our results show that understanding long-range regulation of nuclear receptors can provide key insight into their functional roles as well as evolutionary history; and this strongly merits further study. PMID:24551185

Sharma, Yogita; Chilamakuri, Chandra Sekhar Reddy; Bakke, Marit; Lenhard, Boris

2014-01-01

220

Cloning of human genes encoding novel G protein-coupled receptors  

SciTech Connect

We report the isolation and characterization of several novel human genes encoding G protein-coupled receptors. Each of the receptors contained the familiar seven transmembrane topography and most closely resembled peptide binding receptors. Gene GPR1 encoded a receptor protein that is intronless in the coding region and that shared identity (43% in the transmembrane regions) with the opioid receptors. Northern blot analysis revealed that GPR1 transcripts were expressed in the human hippocampus, and the gene was localized to chromosome 15q21.6. Gene GPR2 encoded a protein that most closely resembled an interleukin-8 receptor (51% in the transmembrane regions), and this gene, not expressed in the six brain regions examined, was localized to chromosome 17q2.1-q21.3. A third gene, GPR3, showed identity (56% in the transmembrane regions) with a previously characterized cDNA clone from rat and was localized to chromosome 1p35-p36.1. 31 refs., 5 figs., 1 tab.

Marchese, A.; Docherty, J.M.; Heiber, M. [Univ. of Toronto, (Canada)] [and others] [Univ. of Toronto, (Canada); and others

1994-10-01

221

Adoptive Immunotherapy for Hematological Malignancies Using T Cells Gene-Modified to Express Tumor Antigen-Specific Receptors  

PubMed Central

Accumulating clinical evidence suggests that adoptive T-cell immunotherapy could be a promising option for control of cancer; evident examples include the graft-vs-leukemia effect mediated by donor lymphocyte infusion (DLI) and therapeutic infusion of ex vivo-expanded tumor-infiltrating lymphocytes (TIL) for melanoma. Currently, along with advances in synthetic immunology, gene-modified T cells retargeted to defined tumor antigens have been introduced as “cellular drugs”. As the functional properties of the adoptive immune response mediated by T lymphocytes are decisively regulated by their T-cell receptors (TCRs), transfer of genes encoding target antigen-specific receptors should enable polyclonal T cells to be uniformly redirected toward cancer cells. Clinically, anticancer adoptive immunotherapy using genetically engineered T cells has an impressive track record. Notable examples include the dramatic benefit of chimeric antigen receptor (CAR) gene-modified T cells redirected towards CD19 in patients with B-cell malignancy, and the encouraging results obtained with TCR gene-modified T cells redirected towards NY-ESO-1, a cancer-testis antigen, in patients with advanced melanoma and synovial cell sarcoma. This article overviews the current status of this treatment option, and discusses challenging issues that still restrain the full effectiveness of this strategy, especially in the context of hematological malignancy. PMID:25517545

Fujiwara, Hiroshi

2014-01-01

222

Evolution of a Bitter Taste Receptor Gene Cluster in a New World Sparrow  

PubMed Central

Bitter taste perception likely evolved as a protective mechanism against the ingestion of harmful compounds in food. The evolution of the taste receptor type 2 (TAS2R) gene family, which encodes the chemoreceptors that are directly responsible for the detection of bitter compounds, has therefore been of considerable interest. Though TAS2R repertoires have been characterized for a number of species, to date the complement of TAS2Rs from just one bird, the chicken, which had a notably small number of TAS2Rs, has been established. Here, we used targeted mapping and genomic sequencing in the white-throated sparrow (Zonotrichia albicollis) and sample sequencing in other closely related birds to reconstruct the history of a TAS2R gene cluster physically linked to the break points of an evolutionary chromosomal rearrangement. In the white-throated sparrow, this TAS2R cluster encodes up to 18 functional bitter taste receptors and likely underwent a large expansion that predates and/or coincides with the radiation of the Emberizinae subfamily into the New World. In addition to signatures of gene birth-and-death evolution within this cluster, estimates of Ka/Ks for the songbird TAS2Rs were similar to those previously observed in mammals, including humans. Finally, comparison of the complete genomic sequence of the cluster from two common haplotypes in the white-throated sparrow revealed a number of nonsynonymous variants and differences in functional gene content within this species. These results suggest that interspecies and intraspecies genetic variability does exist in avian TAS2Rs and that these differences could contribute to variation in bitter taste perception in birds. PMID:20624740

Davis, Jamie K.; Lowman, Josh J.; Thomas, Pamela J.; ten Hallers, Boudewijn F. H.; Koriabine, Maxim; Huynh, Lynn Y.; Maney, Donna L.; de Jong, Pieter J.; Martin, Christa L.; Thomas, James W.

2010-01-01

223

Molecular characterization, expression profile, and polymorphism of goose dopamine D1 receptor gene.  

PubMed

Dopamine D1 receptor (DRD1) is one of the dopamine receptors with seven transmembrane domains that are coupled to the G protein. In the present study, we cloned the full coding region of DRD1 gene by the reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends from the goose hypothalamus tissues. Results showed that the goose DRD1 cDNA (GenBank: KF156790) contained a 1,356 bp open reading frame encoding a protein 452 amino acid with a molecular weight of 50.52 kDa and a isoelectric point of 6.96. Bioinformatics analysis indicated that the deduced amino acid sequence was 71-98% identical to the DRD1 protein of other species, contained seven transmembrane domains and four N-glycosylation sites. A phylogenetic tree analysis revealed that the deduced goose DRD1 protein had a close genetic relationship and evolutional distance with that of duck, chicken, and zebra finch. The semi-quantitative RT-PCR analysis displayed goose DRD1 gene was widely expressed in all detected tissues, including heart, lung, liver, spleen, kidney, breast muscle, duodenum, sebum, pituitary, hypothalamus, ovary and oviduct. Eighteen single nucleotide polymorphisms were indentified in 3,169 bp length of this gene. For G90A mutation, the genotyping analysis of PCR-TspRI-RFLP showed the allele G was in dominance in all detected goose breeds, and the allele frequencies of this polymorphism were significantly different between Chinese goose breeds and foreign breeds (P<0.01). These findings will help us understand the functions of the DRD1 gene and the molecular breeding in geese. PMID:24452723

Wang, Cui; Liu, Yi; Wang, Huiying; Wu, Huali; Gong, Shaoming; He, Daqian

2014-05-01

224

Evolution of a bitter taste receptor gene cluster in a New World sparrow.  

PubMed

Bitter taste perception likely evolved as a protective mechanism against the ingestion of harmful compounds in food. The evolution of the taste receptor type 2 (TAS2R) gene family, which encodes the chemoreceptors that are directly responsible for the detection of bitter compounds, has therefore been of considerable interest. Though TAS2R repertoires have been characterized for a number of species, to date the complement of TAS2Rs from just one bird, the chicken, which had a notably small number of TAS2Rs, has been established. Here, we used targeted mapping and genomic sequencing in the white-throated sparrow (Zonotrichia albicollis) and sample sequencing in other closely related birds to reconstruct the history of a TAS2R gene cluster physically linked to the break points of an evolutionary chromosomal rearrangement. In the white-throated sparrow, this TAS2R cluster encodes up to 18 functional bitter taste receptors and likely underwent a large expansion that predates and/or coincides with the radiation of the Emberizinae subfamily into the New World. In addition to signatures of gene birth-and-death evolution within this cluster, estimates of Ka/Ks for the songbird TAS2Rs were similar to those previously observed in mammals, including humans. Finally, comparison of the complete genomic sequence of the cluster from two common haplotypes in the white-throated sparrow revealed a number of nonsynonymous variants and differences in functional gene content within this species. These results suggest that interspecies and intraspecies genetic variability does exist in avian TAS2Rs and that these differences could contribute to variation in bitter taste perception in birds. PMID:20624740

Davis, Jamie K; Lowman, Josh J; Thomas, Pamela J; ten Hallers, Boudewijn F H; Koriabine, Maxim; Huynh, Lynn Y; Maney, Donna L; de Jong, Pieter J; Martin, Christa L; Thomas, James W

2010-01-01

225

Association of vitamin D receptor gene polymorphism with the urine calcium level in nephrolithiasis patients.  

PubMed

Association of vitamin D receptor (VDR) gene polymorphism with the urine calcium level in nephrolithiasis patients from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism and urine calcium level in nephrolithiasis patients using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 April 2014, and eligible investigations were included and synthesized using meta-analysis method. Four reports were recruited into this meta-analysis for the association of VDR BsmI, Fok1, TaqI and ApaI gene polymorphism with urine calcium level in nephrolithiasis patients. In this meta-analysis, VDR BsmI B allele and BB genotype, Fok1 f allele and ff genotype, TaqI, and ApaI gene polymorphism were not associated with urine calcium level in nephrolithiasis patients. However, the BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. In conclusion, VDR BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. However, more studies should be conducted to confirm it. PMID:25000366

Zhou, Tian-Biao; Jiang, Zong-Pei; Huang, Miao-Fang; Zhang, Rui

2015-04-01

226

The evolution of vertebrate somatostatin receptors and their gene regions involves extensive chromosomal rearrangements  

PubMed Central

Background Somatostatin and its related neuroendocrine peptides have a wide variety of physiological functions that are mediated by five somatostatin receptors with gene names SSTR1-5 in mammals. To resolve their evolution in vertebrates we have investigated the SSTR genes and a large number of adjacent gene families by phylogeny and conserved synteny analyses in a broad range of vertebrate species. Results We find that the SSTRs form two families that belong to distinct paralogons. We observe not only chromosomal similarities reflecting the paralogy relationships between the SSTR-bearing chromosome regions, but also extensive rearrangements between these regions in teleost fish genomes, including fusions and translocations followed by reshuffling through intrachromosomal rearrangements. These events obscure the paralogy relationships but are still tractable thanks to the many genomes now available. We have identified a previously unrecognized SSTR subtype, SSTR6, previously misidentified as either SSTR1 or SSTR4. Conclusions Two ancestral SSTR-bearing chromosome regions were duplicated in the two basal vertebrate tetraploidizations (2R). One of these ancestral SSTR genes generated SSTR2, -3 and -5, the other gave rise to SSTR1, -4 and -6. Subsequently SSTR6 was lost in tetrapods and SSTR4 in teleosts. Our study shows that extensive chromosomal rearrangements have taken place between related chromosome regions in teleosts, but that these events can be resolved by investigating several distantly related species. PMID:23194088

2012-01-01

227

Association study of GABAA ?2 receptor subunit gene variants in antipsychotic-associated weight gain.  

PubMed

Schizophrenia treatment has been hampered by undesirable adverse effects, including weight gain and associated complications. Recent candidate gene studies have been exploring the appetite regulation pathways in antipsychotic-associated weight gain (AAWG) with some promising leads. Genome-wide association studies of obesity have pointed to a number of potential candidate genes, such as MC4R, that were later found to be shared with AAWG. GABAA ?2 receptor subunit (GABRA2) was another potential candidate gene for obesity from genome-wide association studies; however, it has not been explored in AAWG. We examined 9 single nucleotide polymorphisms across the GABRA2 gene. Prospective weight change was assessed for a total of 160 schizophrenia patients of European ancestry. The rs279858 marker was associated with percent weight change, with the patients homozygous for the TT genotype experiencing higher percentage weight gain on average than the C allele carriers (P = 0.009). When we performed the analysis considering each clinical site using a meta-analytic method, the results remained statistically significant (P = 1.4e-4). These findings became even more significant when we considered only patients taking clozapine or olanzapine, the 2 medications with higher risk for weight gain (P < 1e-10). GABRA2 genetic variants may play a role in predicting AAWG. However, replication in larger and independent samples is required. PMID:25514066

Zai, Clement C H; Tiwari, Arun K; Chowdhury, Nabilah I; Brandl, Eva J; Shaikh, Sajid A; Freeman, Natalie; Lieberman, Jeffrey A; Meltzer, Herbert Y; Müller, Daniel J; Kennedy, James L

2015-02-01

228

Multimodality Imaging of Gene Transfer with a Receptor-Based Reporter Gene  

PubMed Central

Gene therapy trials have traditionally used tumor and tissue biopsies for assessing the efficacy of gene transfer. Non-invasive imaging techniques offer a distinct advantage over tissue biopsies in that the magnitude and duration of gene transfer can be monitored repeatedly. Human somatostatin receptor subtype 2 (SSTR2) has been used for the nuclear imaging of gene transfer. To extend this concept, we have developed a somatostatin receptor–enhanced green fluorescent protein fusion construct (SSTR2-EGFP) for nuclear and fluorescent multimodality imaging. Methods An adenovirus containing SSTR2-EGFP (AdSSTR2-EGFP) was constructed and evaluated in vitro and in vivo. SCC-9 human squamous cell carcinoma cells were infected with AdEGFP, AdSSTR2, or AdSSTR2-EGFP for in vitro evaluation by saturation binding, internalization, and fluorescence spectroscopy assays. In vivo biodistribution and nano-SPECT imaging studies were conducted with mice bearing SCC-9 tumor xenografts directly injected with AdSSTR2-EGFP or AdSSTR2 to determine the tumor localization of 111In-diethylenetriaminepentaacetic acid (DTPA)-Tyr3-octreotate. Fluorescence imaging was conducted in vivo with mice receiving intratumoral injections of AdSSTR2, AdSSTR2-EGFP, or AdEGFP as well as ex vivo with tissues extracted from mice. Results The similarity between AdSSTR2-EGFP and wild-type AdSSTR2 was demonstrated in vitro by the saturation binding and internalization assays, and the fluorescence emission spectra of cells infected with AdSSTR2-EGFP was almost identical to the spectra of cells infected with wild-type AdEGFP. Biodistribution studies demonstrated that the tumor uptake of 111In-DTPA-Tyr3-octreotate was not significantly different (P > 0.05) when tumors (n = 5) were injected with AdSSTR2 or AdSSTR2-EGFP but was significantly greater than the uptake in control tumors. Fluorescence was observed in tumors injected with AdSSTR2-EGFP and AdEGFP in vivo and ex vivo but not in tumors injected with AdSSTR2. Although fluorescence was observed, there were discrepancies between in vivo imaging and ex vivo imaging as well as between nuclear imaging and fluorescent imaging. Conclusion These studies showed that the SSTR2-EGFP fusion construct can be used for in vivo nuclear and optical imaging of gene transfer. PMID:20720053

Chen, Ron; Parry, Jesse J.; Akers, Walter J.; Berezin, Mikhail Y.; El Naqa, Issam M.; Achilefu, Samuel; Edwards, W. Barry; Rogers, Buck E.

2010-01-01

229

Glucocorticoid regulation of insulin receptor gene transcription in IM-9 cultured lymphocytes.  

PubMed Central

We have reported that glucocorticoids increase steady state insulin receptor mRNA levels in target cells. In the present study using IM-9 cultured human lymphocytes, we investigated the mechanism responsible for this glucocorticoid mediated increase in insulin receptor mRNA levels. Incubation of IM-9 cells with 100 nM dexamethasone for 4 h stimulated a parallel increase in both polysomal and nuclear insulin receptor RNAs indicating that glucocorticoids did not alter the nuclear transport of insulin receptor RNA. Dexamethasone did not alter insulin receptor mRNA half life (t 1/2 = 140 +/- 20 min), indicating that glucocorticoids did not influence mRNA stability. Furthermore, the dexamethasone-induced increase in insulin receptor mRNA levels was not blocked by pretreatment of cells with cycloheximide indicating that the glucocorticoid effect was independent of new protein synthesis. When the labeled transcripts from nuclear run-off incubations were then hybridized to immobilize human insulin receptor cDNA, a three- to fourfold increase in transcriptional activity was observed. This transcriptional effect occurred before the increase in steady state insulin receptor mRNA levels and over the same range of dexamethasone concentrations. These studies indicate therefore a direct effect of glucocorticoids on insulin receptor gene transcription, and demonstrate that the insulin receptor gene is under hormonal control. Images PMID:3339130

McDonald, A R; Goldfine, I D

1988-01-01

230

Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia.  

PubMed

Rare copy number variants (CNVs) have a prominent role in the aetiology of schizophrenia and other neuropsychiatric disorders. Substantial risk for schizophrenia is conferred by large (>500-kilobase) CNVs at several loci, including microdeletions at 1q21.1 (ref. 2), 3q29 (ref. 3), 15q13.3 (ref. 2) and 22q11.2 (ref. 4) and microduplication at 16p11.2 (ref. 5). However, these CNVs collectively account for a small fraction (2-4%) of cases, and the relevant genes and neurobiological mechanisms are not well understood. Here we performed a large two-stage genome-wide scan of rare CNVs and report the significant association of copy number gains at chromosome 7q36.3 with schizophrenia. Microduplications with variable breakpoints occurred within a 362-kilobase region and were detected in 29 of 8,290 (0.35%) patients versus 2 of 7,431 (0.03%) controls in the combined sample. All duplications overlapped or were located within 89 kilobases upstream of the vasoactive intestinal peptide receptor gene VIPR2. VIPR2 transcription and cyclic-AMP signalling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. These findings implicate altered vasoactive intestinal peptide signalling in the pathogenesis of schizophrenia and indicate the VPAC2 receptor as a potential target for the development of new antipsychotic drugs. PMID:21346763

Vacic, Vladimir; McCarthy, Shane; Malhotra, Dheeraj; Murray, Fiona; Chou, Hsun-Hua; Peoples, Aine; Makarov, Vladimir; Yoon, Seungtai; Bhandari, Abhishek; Corominas, Roser; Iakoucheva, Lilia M; Krastoshevsky, Olga; Krause, Verena; Larach-Walters, Verónica; Welsh, David K; Craig, David; Kelsoe, John R; Gershon, Elliot S; Leal, Suzanne M; Dell Aquila, Marie; Morris, Derek W; Gill, Michael; Corvin, Aiden; Insel, Paul A; McClellan, Jon; King, Mary-Claire; Karayiorgou, Maria; Levy, Deborah L; DeLisi, Lynn E; Sebat, Jonathan

2011-03-24

231

(AAT)n repeat in the cannabinoid receptor gene, CNR1: association with schizophrenia in a Spanish population  

Microsoft Academic Search

The cannabinoid receptor 1 gene (CNR1) has been associated with addictive disorders and schizophrenia in different studies. We have compared the frequencies of\\u000a the alleles for the 3?-UTR CNR1 microsatellite in a sample of 113 Spanish schizophrenic patients, including 68 with comorbid substance abuse, and 111 healthy\\u000a controls. We report that the frequency of the allele 4 of this microsatellite

Isabel Martínez-Gras; Janet Hoenicka; Guillermo Ponce; Miguel Angel Jiménez-Arriero; Elena Pérez-Hernandez; Israel Ampuero; Jose Antonio Ramos-Atance; Tomas Palomo; Gabriel Rubio

2006-01-01

232

Variants in the Dopamine-4-Receptor Gene Promoter Are Not Associated with Sensation Seeking in Skiers  

PubMed Central

Sensation seeking is a personality trait that has been associated with disinhibited behaviours including substance use and gambling, but also with high-risk sport practices including skydiving, paragliding, and downhill skiing. Twin studies have shown that sensation seeking is moderately heritable, and candidate genes encoding components involved in dopaminergic transmission have been investigated as contributing to this type of behaviour. To determine whether variants in the regulatory regions of the dopamine-4-receptor gene (DRD4) influenced sport-specific sensation seeking, we analyzed five polymorphisms (?1106T/C, ?906T/C, ?809G/A, ?291C/T, 120-bp duplication) in the promoter region of the gene in a cohort of skiers and snowboarders (n?=?599) that represented a broad range of sensation seeking behaviours. We grouped subjects by genotype at each of the five loci and compared impulsive sensation seeking and domain-specific (skiing) sensation seeking between groups. There were no significant associations between genotype(s) and general or domain-specific sensation seeking in the skiers and snowboarders, suggesting that while DRD4 has previously been implicated in sensation seeking, the promoter variants investigated in this study do not contribute to sensation seeking in this athlete population. PMID:24691022

Thomson, Cynthia J.; Rajala, Amelia K.; Carlson, Scott R.; Rupert, Jim L.

2014-01-01

233

The low density lipoprotein receptor-related protein 1: Unique tissue-specific functions revealed by selective gene knockout studies  

PubMed Central

The low-density lipoprotein (LDL) receptor-related protein (originally called LRP, but now referred to as LRP1) is a large endocytic receptor that is widely expressed in several tissues. LRP1 is a member of the LDL receptor family that plays diverse roles in various biological processes including lipoprotein metabolism, degradation of proteases, activation of lysosomal enzymes and cellular entry of bacterial toxins and viruses. Deletion of the LRP1 gene leads to lethality in mice, revealing a critical, but as of yet, undefined role in development. Tissue-specific gene deletion studies reveal an important contribution of LRP1 in the vasculature, central nervous system, in macrophages and in adipocytes. Three important properties of LRP1 dictate its diverse role in physiology: first, its ability to recognize more than thirty distinct ligands; second, its ability to bind a large number of cytoplasmic adaptor proteins via determinants located on its cytoplasmic domain in a phosphorylation-specific manner; and third, its ability to associate with and modulate the activity of other transmembrane receptors such as integrins and receptor tyrosine kinases. PMID:18626063

Lillis, Anna P.; Van Duyn, Lauren B.; Murphy-Ullrich, Joanne E.; Strickland, Dudley K.

2008-01-01

234

Definition of the cattle killer cell Ig-like receptor gene family: comparison with aurochs and human counterparts.  

PubMed

Under selection pressure from pathogens, variable NK cell receptors that recognize polymorphic MHC class I evolved convergently in different species of placental mammal. Unexpectedly, diversified killer cell Ig-like receptors (KIRs) are shared by simian primates, including humans, and cattle, but not by other species. Whereas much is known of human KIR genetics and genomics, knowledge of cattle KIR is limited to nine cDNA sequences. To facilitate comparison of the cattle and human KIR gene families, we determined the genomic location, structure, and sequence of two cattle KIR haplotypes and defined KIR sequences of aurochs, the extinct wild ancestor of domestic cattle. Larger than its human counterpart, the cattle KIR locus evolved through successive duplications of a block containing ancestral KIR3DL and KIR3DX genes that existed before placental mammals. Comparison of two cattle KIR haplotypes and aurochs KIR show the KIR are polymorphic and the gene organization and content appear conserved. Of 18 genes, 8 are functional and 10 were inactivated by point mutation. Selective inactivation of KIR3DL and activating receptor genes leaves a functional cohort of one inhibitory KIR3DL, one activating KIR3DX, and six inhibitory KIR3DX. Functional KIR diversity evolved from KIR3DX in cattle and from KIR3DL in simian primates. Although independently evolved, cattle and human KIR gene families share important function-related properties, indicating that cattle KIR are NK cell receptors for cattle MHC class I. Combinations of KIR and MHC class I are the major genetic factors associated with human disease and merit investigation in cattle. PMID:25398326

Sanderson, Nicholas D; Norman, Paul J; Guethlein, Lisbeth A; Ellis, Shirley A; Williams, Christina; Breen, Matthew; Park, Steven D E; Magee, David A; Babrzadeh, Farbod; Warry, Andrew; Watson, Mick; Bradley, Daniel G; MacHugh, David E; Parham, Peter; Hammond, John A

2014-12-15

235

Definition of the Cattle Killer Cell Ig–like Receptor Gene Family: Comparison with Aurochs and Human Counterparts  

PubMed Central

Under selection pressure from pathogens, variable NK cell receptors that recognize polymorphic MHC class I evolved convergently in different species of placental mammal. Unexpectedly, diversified killer cell Ig–like receptors (KIRs) are shared by simian primates, including humans, and cattle, but not by other species. Whereas much is known of human KIR genetics and genomics, knowledge of cattle KIR is limited to nine cDNA sequences. To facilitate comparison of the cattle and human KIR gene families, we determined the genomic location, structure, and sequence of two cattle KIR haplotypes and defined KIR sequences of aurochs, the extinct wild ancestor of domestic cattle. Larger than its human counterpart, the cattle KIR locus evolved through successive duplications of a block containing ancestral KIR3DL and KIR3DX genes that existed before placental mammals. Comparison of two cattle KIR haplotypes and aurochs KIR show the KIR are polymorphic and the gene organization and content appear conserved. Of 18 genes, 8 are functional and 10 were inactivated by point mutation. Selective inactivation of KIR3DL and activating receptor genes leaves a functional cohort of one inhibitory KIR3DL, one activating KIR3DX, and six inhibitory KIR3DX. Functional KIR diversity evolved from KIR3DX in cattle and from KIR3DL in simian primates. Although independently evolved, cattle and human KIR gene families share important function-related properties, indicating that cattle KIR are NK cell receptors for cattle MHC class I. Combinations of KIR and MHC class I are the major genetic factors associated with human disease and merit investigation in cattle. PMID:25398326

Sanderson, Nicholas D.; Norman, Paul J.; Guethlein, Lisbeth A.; Ellis, Shirley A.; Williams, Christina; Breen, Matthew; Park, Steven D. E.; Magee, David A.; Babrzadeh, Farbod; Warry, Andrew; Watson, Mick; Bradley, Daniel G.; MacHugh, David E.; Parham, Peter

2014-01-01

236

Polymorphism in the Protease Activated Receptor-4 Gene Region Associates with Platelet Activation and Perioperative Myocardial Injury  

PubMed Central

Background Protease activated receptors (PAR) ?1 and ?4 are the principal receptors for thrombin-mediated platelet activation. Functional genetic variation has been described in the human PAR1 gene, but not in the PAR4 gene (F2RL3). We sought to identify variants in and around F2RL3 and to determine their association with perioperative myocardial injury (PMI) after coronary artery bypass graft surgery. We further explored possible mechanisms for F2RL3 SNP associations with PMI including altered receptor expression and platelet activation. Methods and Results Twenty-three single nucleotide polymorphisms (SNPs) in the F2RL3 gene region were genotyped in two phases in 934 Caucasian subjects. Platelets from 43 subjects (23 major allele, 20 risk allele) homozygous for rs773857 (SNP with the strongest association with PMI) underwent flow cytometry to assess PAR4 receptor number and response to activation by a specific PAR4 activating peptide (AYPGKF) measured by von Willebrand factor (vWf) binding and P-selectin release and PAC-1 binding. We identified a novel association of SNP rs773857 with PMI (OR 2.4, P=0.004). rs773857 risk allele homozygotes have significantly increased platelet counts and platelets showed a significant increase in P-selectin release after activation (P=0.004). Conclusion We conclude that rs773857 risk allele homozygotes are associated with risk for increased platelet count and hyperactivity. PMID:22228373

Muehlschlegel, Jochen D.; Perry, Tjörvi E.; Liu, Kuang-Yu; Fox, Amanda A.; Smith, Shane; Lichtner, Peter; Collard, Charles D.; Shernan, Stanton K.; Hartwig, John H.; Body, Simon C.; Hoffmeister, Karin M.

2015-01-01

237

Molecular Identification and Expressive Characterization of an Olfactory Co-Receptor Gene in the Asian Honeybee, Apis cerana cerana  

PubMed Central

Olfaction recognition process is extraordinarily complex in insects, and the olfactory receptors play an important function in the process. In this paper, a highly conserved olfactory co-receptor gene, AcerOr2 (ortholog to the Drosophila melanogaster Or83b), cloned from the antennae of the Asian honeybee, Apis cerana cerana Fabricius (Hymenoptera: Apidae), using reverse transcriptase PCR and rapid amplification of cDNA ends. The full-length sequence of the gene was 1763 bp long, and the cDNA open reading frame encoded 478 amino acid residues, including 7 putative transmembrane domains. Alignment analysis revealed that AcerOr2 shares high homology (> 74%) with similar olfactory receptors found in other Hymenoptera species. The amino acid identity with the closely related species Apis mellifera reached 99.8%. The developmental expression analysis using quantitative real-time reverse transcriptase PCR suggested that the AcerOr2 transcript was expressed at a relatively low level in the larval stage, whereas it was expressed broadly in the pupal and adult stages, with a significantly high level on the days just before and after eclosion. In situ hybridization showed that AcerOr2 mRNA was expressed in sensilla placodea and on the basal region of the worker antennal cuticle, in accordance with the previous conclusions that the conserved genes are expressed in most olfactory receptor neurons. PMID:24224665

Zhao, Huiting; Gao, Pengfei; Zhang, Chunxiang; Ma, Weihua; Jiang, Yusuo

2013-01-01

238

CC chemokine receptor 5 gene polymorphisms in beryllium disease  

PubMed Central

CC chemokine receptor 5 (CCR5) is expressed on type-1 T-helper cells, which are involved in the pathogenesis of the granulomatous lung disease chronic beryllium disease (CBD). CCR5 gene (CCR5) polymorphisms are associated with sarcoidosis severity. The present study explores associations between CCR5 polymorphisms and CBD and its disease progression. Eight CCR5 polymorphisms were genotyped in CBD (n = 88), beryllium sensitisation (BeS; n = 86) and beryllium-exposed nondiseased controls (n = 173) using PCR with sequence-specific primers. Pulmonary function and bronchoalveolar lavage data were examined for associations with genotypes. There were no significant differences in genotype and allele frequency between CBD, BeS individuals and controls. In CBD, associations were found with decline in forced expiratory volume in 1 s and forced vital capacity and the CCR5 -3458 thymidine (T)T genotype (p<0.0001), and an increase in alveolar–arterial oxygen tension difference at rest (p = 0.003) and at maximum exercise (p = 0.01) and the -5663 adenine allele. Increased bronchoalveolar lavage lymphocyte numbers were associated with CCR5 -2459 guanine/-2135T (p = 0.01) only in the combined CBD and BeS group. This is the first study showing that CCR5 polymorphisms are associated with worsening pulmonary function over time in CBD, suggesting that CCR5 is important in the progression of pulmonary function in CBD. Further studies would be useful to clarify the mechanism whereby CCR5 polymorphisms affect progression of CBD. PMID:20075058

Sato, H.; Silveira, L.; Spagnolo, P.; Gillespie, M.; Gottschall, E.B.; Welsh, K.I.; Bois, R.M. du; Newman, L.S.; Maier, L.A.

2011-01-01

239

CC chemokine receptor 5 gene polymorphisms in beryllium disease.  

PubMed

CC chemokine receptor 5 (CCR5) is expressed on type-1 T-helper cells, which are involved in the pathogenesis of the granulomatous lung disease chronic beryllium disease (CBD). CCR5 gene (CCR5) polymorphisms are associated with sarcoidosis severity. The present study explores associations between CCR5 polymorphisms and CBD and its disease progression. Eight CCR5 polymorphisms were genotyped in CBD (n = 88), beryllium sensitisation (BeS; n = 86) and beryllium-exposed nondiseased controls (n = 173) using PCR with sequence-specific primers. Pulmonary function and bronchoalveolar lavage data were examined for associations with genotypes. There were no significant differences in genotype and allele frequency between CBD, BeS individuals and controls. In CBD, associations were found with decline in forced expiratory volume in 1 s and forced vital capacity and the CCR5 -3458 thymidine (T)T genotype (p<0.0001), and an increase in alveolar-arterial oxygen tension difference at rest (p = 0.003) and at maximum exercise (p = 0.01) and the -5663 adenine allele. Increased bronchoalveolar lavage lymphocyte numbers were associated with CCR5 -2459 guanine/-2135T (p = 0.01) only in the combined CBD and BeS group. This is the first study showing that CCR5 polymorphisms are associated with worsening pulmonary function over time in CBD, suggesting that CCR5 is important in the progression of pulmonary function in CBD. Further studies would be useful to clarify the mechanism whereby CCR5 polymorphisms affect progression of CBD. PMID:20075058

Sato, H; Silveira, L; Spagnolo, P; Gillespie, M; Gottschall, E B; Welsh, K I; du Bois, R M; Newman, L S; Maier, L A

2010-08-01

240

Assignment of the Human Gene for the Low Density Lipoprotein Receptor to Chromosome 19: Synteny of a Receptor, a Ligand, and a Genetic Disease  

Microsoft Academic Search

The availability of a species-specific monoclonal antibody that recognizes the low density lipoprotein (LDL) receptor of human but not hamster origin permitted assignment of the structural gene for the human receptor to chromosome 19. The antibody was used to detect the human LDL receptor in a series of hamster-human somatic cell hybrids by two assays: (i) a structural assay that

Uta Francke; Michael S. Brown; Joseph L. Goldstein

1984-01-01

241

CAG Repeat Number in the Androgen Receptor Gene and Prostate Cancer  

PubMed Central

Prostate cancer (PC) is the second leading cause of cancer deaths in men. The effects of androgens on prostatic tissue are mediated by the androgen receptor (AR) gene. The 5? end of exon 1 of the AR gene includes a polymorphic CAG triplet repeat that numbers between 10 to 36 in the normal population. The length of the CAG repeats is inversely related to the transactivation function of the AR gene. There is controversy over association between short CAG repeat numbers in the AR gene and PC. This retrospective case-control study evaluates the possible effect of short CAG repeats on the AR gene in prostate cancer risk in Macedonian males. A total of 392 male subjects, 134 PC patients, 106 patients with benign prostatic hyperplasia (BPH) and 152 males from the general Macedonian population were enrolled in this study. The CAG repeat length was determined by fluorescent polymerase chain reaction (PCR) amplification of exon1 of the AR gene followed by capillary electrophoresis (CE) on a genetic analyzer. The mean repeat length in PC patients was 21.5 ± 2.65, in controls 22.28 ± 2.86 (p = 0.009) and in BPH patients 22.1 ± 2.52 (p = 0.038). Short CAG repeats (<19) were found in 21.64% of PC patients vs. 9.43% in BPH patients (p = 0.0154). We also found an association of low Gleason score (<7) with short CAG repeat (<19) in PC patients (p = 0.0306), and no association between the age at diagnosis of PC and BPH and CAG repeat length. These results suggest that reduced CAG repeat length may be associated with increased prostate cancer risk in Macedonian men. PMID:24052720

Madjunkova, S; Eftimov, A; Georgiev, V; Petrovski, D; Dimovski, AJ; Plaseska-Karanfilska, D

2012-01-01

242

?-casomorphin-7 alters ?-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis.  

PubMed

Atopic dermatitis (AD) is a chronic inflammatory skin disease with heterogeneous clinical phenotypes reflecting genetic predisposition and exposure to environmental factors. Reactions to food may play a significant role especially in young children. Milk proteins are particularly strong allergens and are additional source of bioactive peptides including ?-casomorphin-7 (BCM7, Tyr-Pro-Phe-Pro-Gly-Pro-Ile). BCM7 exerts its influence on nervous, digestive, and immune functions via the ?-opioid receptor (MOR). Proline dipeptidyl peptidase IV (DPPIV; EC 3.4.14.5) appears to be the primary degrading enzyme of BCM7. Moreover, DPPIV is known to restrict activity of proinflammatory peptides. BCM7 is considered to modulate an immune response by affecting MOR and DPPIV genes expression. In this study, we determined the MOR and DPPIV genes expression in children diagnosed with a severe form of AD. 40 healthy children and 62 children diagnosed with severe AD (AD score ?60) were included in the study. Peripheral blood mononuclear cells (PBMCs) from the studied subjects were incubated with the peptide extracts of raw and hydrolysed cow milk with defined ?-casein genotypes (A1A1, A2A2 and A1A2) and MOR and DPPIV genes expression was determined with real-time PCR. Incubation PBMCs with peptide extracts from cow milk caused an increase of the MOR gene expression (p<0.05; p<0.001) in AD children with a simultaneous decrease in the DPPIV gene expression (p<0.001). The obtained results supplement the knowledge on the BCM7 participation in AD etiology and provide an important diagnostic tool. PMID:25281794

Fiedorowicz, Ewa; Kaczmarski, Maciej; Cie?li?ska, Anna; Sienkiewicz-Sz?apka, Edyta; Jarmo?owska, Beata; Chwa?a, Barbara; Kostyra, El?bieta

2014-12-01

243

The cps gene cluster of Salmonella strain LT2 includes a second mannose pathway: sequence of two genes and relationship to genes in the rfb gene cluster  

Microsoft Academic Search

We report the presence in Salmonella enterica strain LT2 (serovar thyphimurium) of duplicate genes for two steps in the synthesis of GDP-mannose. The previously known genes, rfbK (phosphomannomutase) and rfbM (mannose-l-phosphate guanyltransferase), are part of the gene cluster for the O antigen. The two new genes, cpsB and cpsG, respectively, are thought to be part of the gene cluster for

Gordon Stevenson; Sang Jun Lee; Lajwant K. Romana; Peter R. Reeves

1991-01-01

244

Expression of the transferrin receptor gene during the process of mononuclear phagocyte maturation  

SciTech Connect

The expression of transferrin receptors by blood monocytes, human alveolar macrophages, and in vitro matured macrophages was evaluated by immunofluorescence, radioligand binding, and Northern analysis, using the monoclonal anti-human transferrin receptor antibody OKT9, (/sup 125/I)-labeled human transferrin and a (/sup 32/P)-labeled human transferrin receptor cDNA probe, respectively. By immunofluorescence, the majority of alveolar macrophages expressed transferrin receptors (86 +/- 3%). The radioligand binding assay demonstrated the affinity constant (K/sub a/) of the alveolar macrophage transferrin receptor was 4.4 +/- 0.7 x 10/sup 8/ M/sup -1/, and the number of receptors per cell was 4.4 +/- 1.2 x 10/sup 4/. In marked contrast, transferrin receptors were not present on the surface or in the cytoplasm of blood monocytes, the precursors of the alveolar macrophages. However, when monocytes were cultured in vitro and allowed to mature, > 80% expressed transferrin receptors by day 6, and the receptors could be detected by day 3. Consistent with these observations, a transferrin receptor mRNA with a molecular size of 4.9 kb was demonstrated in alveolar macrophages and in vitro matured macrophages but not in blood monocytes. Thus, although blood monocytes do not express the transferrin receptor gene, it is expressed by mature macrophages, an event that probably occurs relatively early in the process of monocyte differentiation to macrophages.

Hirata, T.; Bitterman, P.B.; Mornex, J.; Crystal, R.G.

1986-02-15

245

Killer-cell Immunoglobulin-like Receptor gene linkage and copy number variation analysis by droplet digital PCR.  

PubMed

The Killer-cell Immunoglobulin-like Receptor (KIR) gene complex has considerable biomedical importance. Patterns of polymorphism in the KIR region include variability in the gene content of haplotypes and diverse structural arrangements. Droplet digital PCR (ddPCR) was used to identify different haplotype motifs and to enumerate KIR copy number variants (CNVs). ddPCR detected a variety of KIR haplotype configurations in DNA from well-characterized cell lines. Mendelian segregation of ddPCR-estimated KIR2DL5 CNVs was observed in Gambian families and CNV typing of other KIRs was shown to be accurate when compared to an established quantitative PCR method. PMID:24597950

Roberts, Chrissy H; Jiang, Wei; Jayaraman, Jyothi; Trowsdale, John; Holland, Martin J; Traherne, James A

2014-01-01

246

Psychoneuroendocrinology . Author manuscript Possible association between the androgen receptor gene and autism  

E-print Network

receptor gene and autism spectrum disorder Susanne Henningsson 1 * , Lina Jonsson 1 , Elin Ljunggren 1.henningsson@pharm.gu.se > Abstract Summary Autism is a highly heritable disorder but the specific genes involved remain largely unknown. The higher prevalence of autism in men than in women, in conjunction with a number of other

Paris-Sud XI, Université de

247

Gene regulation by endogenous thyroid hormone receptors in intestinal epithelial cells  

Microsoft Academic Search

Introduction: Studies in knockout mice indicate that the levels of intestinal alkaline phosphatase (IAP) are a key determinant of the efficiency of dietary fat absorption and the subsequent development of obesity. IAP is a known target gene for thyroid hormone (T3), but no previous studies have examined the ability of endogenous T3 receptors to regulate the IAP gene.Methods: These studies

Fuad Alkhoury; Madhu Malo; Premraj Pushpakaran; Wenying Zhang; Elizabeth Fleming; Moushumi Mozumder; Richard Hodin

2004-01-01

248

The Estrogen Receptor Locus is Associated with a Major Gene Influencing Litter Size in Pigs  

Microsoft Academic Search

Identification of individual major genes affecting quantitative traits in livestock species has been limited to date. By using a candidate gene approach and a divergent breed cross involving the Chinese Meishan pig, we have shown that a specific allele of the estrogen receptor (ER) locus is associated with increased litter size. Female pigs from synthetic lines with a 50% Meishan

Max Rothschild; Carol Jacobson; David Vaske; Christopher Tuggle; Lizhen Wang; Tom Short; Gregg Eckardt; Shoji Sasaki; Amy Vincent; David McLaren; Olwen Southwood; Hein van der Steen; Alan Mileham; Graham Plastow

1996-01-01

249

Host resistance to infection: genetic control of lipopolysaccharide responsiveness by Toll-like receptor genes  

Microsoft Academic Search

Gram-negative bacterial lipopolysaccharide evokes a protective inflammatory response in the normal host. Through genetic analysis of mutant mice, the gene encoding Toll-like receptor 4 (Tlr4) was recently identified as a critical component of this host defense mechanism. Tlr4 is a member of an ancient gene family that regulates antimicrobial host defense in plants, invertebrates and mammals.

Salman T Qureshi; Philippe Gros; Danielle Malo

1999-01-01

250

The First Intron of the Human Growth Hormone Gene Contains a Binding Site for Glucocorticoid Receptor  

Microsoft Academic Search

Glucocorticoid receptor (GCR) protein stimulates transcription from a variety of cellular genes. We show here that GCR partially purified from rat liver binds specifically to a site within the first intron of the human growth hormone (hGH) gene, ≈ 100 base pairs downstream from the start of hGH transcription. GCR binding is selectively inhibited by methylation of two short, symmetrically

David D. Moore; Andrew R. Marks; Douglas I. Buckley; Geoffrey Kapler; Farhang Payvar; Howard M. Goodman

1985-01-01

251

Localization of the acetylcholine receptor ? subunit gene to human chromosome 2q32?qter  

Microsoft Academic Search

The nicotinic acetylcholine receptor of skeletal muscle (CHRN in man, Acr in mouse) is a transmembrane protein composed of four different subunits (?, ?, ?, and ?) assembled into the pentamer ?2???. These subunits are encoded by separate genes which derive from a common ancestral gene by duplication. We have used a murine full-length 1,900-bp-long cDNA encoding the ? subunit

O. C. Cohen-Haguenauer; P. J. R. Barton; A. Buonanno; Nguyen Van Cong; M. Masset; M. F. de Tand; J. Merlie; J. Frézal

1989-01-01

252

D4 receptor gene variation modulates activation of prefrontal cortex during working memory  

Microsoft Academic Search

It has been shown that dopamine (DA) influences performance on neurocognitive tests, which are thought to rely on prefrontal activity. The purpose of this study was to explore the effects of gene polymorphisms related to DA activity, namely the D4 DA receptor (DRD4) gene exon III polymorphisms, on prefrontal cortex (PFC) activation. In this study we measured the brain oxygenation

M. J. Herrmann; A. Walter; T. Schreppel; A.-C. Ehlis; P. Pauli; K.-P. Lesch; A. J. Fallgatter

2007-01-01

253

REPRODUCTIONRESEARCH Gonadotropin-inhibitory hormone (GnIH) receptor gene is  

E-print Network

REPRODUCTIONRESEARCH Gonadotropin-inhibitory hormone (GnIH) receptor gene is expressed of RFamide peptides with a C-terminal Pro-Xaa-Arg-Phe- NH2 motif. The gene encoding a precursor protein) neurons are exclusively found in the hypothalamic paraventricular nucleus while GnIH-ir fibers are found

Ramachandran, Ramesh

254

Evolution of olfactory receptor genes in the human genome  

E-print Network

tandem arrays of OR genes that are phylogenetically closely related. These genes appear to have been generated by tandem gene duplication. However, the relationships between genomic clusters and phylo- genetic a signaling cascade. Mammalian OR genes are expressed mainly in sensory neurons of olfactory epithelium

Nei, Masatoshi

255

Structure and linkage of the D2 dopamine receptor and neural cell adhesion molecule genes on human chromosome 11q23  

SciTech Connect

The gene encoding the D2 dopamine receptor (DRD2) is located on human chromosome 11q23 and has been circumstantially associated with a number of human disorders including Parkinson's disease, schizophrenia, and susceptibility to alcoholism. To determine the physical structure of the DRD2 gene, the authors utilized cosmid cloning, isolation of yeast artificial chromosomes (YACs), and pulsed-field gel electrophoresis to construct a long-range physical map of human chromosome 11q23 linking the genes for the DRD2 and neural cell adhesion molecule (NCAM). The D2 dopamine receptor gene extends over 270 kb and includes an intron of approximately 250 kb separating the putative first exon from the exons encoding the receptor protein. The resulting physical map spans more than 1.5 mb of chromosome band 11q23 and links the DRD2 gene with the gene encoding the NCAM located 150 kb 3[prime] of the DRD2 gene and transcribed from the same DNA strand. They additionally located the sites of at least four hypomethylated HTF islands within the physical map, which potentially indicate the sites of additional genes. High-resolution fluorescent in situ suppression hybridization using cosmid and YAC clones localized this gene cluster between the ApoAI and STMY loci at the interface of bands 11q22.3 and 11q23.1. 40 refs., 6 figs., 2 tabs.

Eubanks, J.H.; Djabali, M.; Selleri, L.; McElligott, D.L.; Evans, G.A. (Salk Institute for Biological Studies, La Jolla, CA (United States)); Grandy, D.K.; Civelli, O. (Oregon Health Sciences Univ., Portland, OR (United States))

1992-12-01

256

Precise mapping of the brain [alpha][sub 2]-adrenergic receptor gene within chromosome 4p16  

SciTech Connect

The gene encoding the brain [alpha][sub 2]-adrenergic receptor (ADRA2C) is located on human chromosome 4. It has been circumstantially associated with a number of human disorders, including Parkinson disease, panic disorders, and Huntington disease (HD). Using somatic cell hybrids, the authors localized the gene to chromosome 4p16 distal to P8 (D4S62). To investigate this locus further, they isolated several cosmid clones covering the entire gene. The gene was found to be intronless. Two (GT)[sub n] repeats in close proximity to the ADRAC2 gene were analyzed and used to define its precise location. Linkage disequilibrium studies of one microsatellite in HD families showed strong nonrandom association to the HD mutation, indicating its tight linkage to the HD gene. The investigation of families carrying recombinant chromosomes, pulsed-field analysis, and genomic walking mapped the ADRAC2 gene adjacent to D4S81, 500 kb proximal to the HD gene. The newly defined microsatellites at the ADRAC2 locus, its precise localization within 4p16, and the detailed PCR conditions facilitate the identification of any defect caused by this gene. 22 refs., 4 figs., 2 tabs.

Riess, O.; Siedlaczck, I.; Potisek, S.; Epplen, J.T. (Ruhr Univ., Bochum (Germany)); Thies, U. (Univ. of Goettingen (Germany)); Graham, R.; Theilmann, J.; Hayden, M.R. (Univ. of British Columbia, Vancouver (Canada)); Grimm, T. (Univ. of Wuerzburg (Germany))

1994-01-15

257

Simulation of E. coli gene regulation including overlapping cell cycles, growth, division, time delays and noise.  

PubMed

Due to the complexity of biological systems, simulation of biological networks is necessary but sometimes complicated. The classic stochastic simulation algorithm (SSA) by Gillespie and its modified versions are widely used to simulate the stochastic dynamics of biochemical reaction systems. However, it has remained a challenge to implement accurate and efficient simulation algorithms for general reaction schemes in growing cells. Here, we present a modeling and simulation tool, called 'GeneCircuits', which is specifically developed to simulate gene-regulation in exponentially growing bacterial cells (such as E. coli) with overlapping cell cycles. Our tool integrates three specific features of these cells that are not generally included in SSA tools: 1) the time delay between the regulation and synthesis of proteins that is due to transcription and translation processes; 2) cell cycle-dependent periodic changes of gene dosage; and 3) variations in the propensities of chemical reactions that have time-dependent reaction rates as a consequence of volume expansion and cell division. We give three biologically relevant examples to illustrate the use of our simulation tool in quantitative studies of systems biology and synthetic biology. PMID:23638057

Luo, Ruoyu; Ye, Lin; Tao, Chenyang; Wang, Kankan

2013-01-01

258

Simulation of E. coli Gene Regulation including Overlapping Cell Cycles, Growth, Division, Time Delays and Noise  

PubMed Central

Due to the complexity of biological systems, simulation of biological networks is necessary but sometimes complicated. The classic stochastic simulation algorithm (SSA) by Gillespie and its modified versions are widely used to simulate the stochastic dynamics of biochemical reaction systems. However, it has remained a challenge to implement accurate and efficient simulation algorithms for general reaction schemes in growing cells. Here, we present a modeling and simulation tool, called ‘GeneCircuits’, which is specifically developed to simulate gene-regulation in exponentially growing bacterial cells (such as E. coli) with overlapping cell cycles. Our tool integrates three specific features of these cells that are not generally included in SSA tools: 1) the time delay between the regulation and synthesis of proteins that is due to transcription and translation processes; 2) cell cycle-dependent periodic changes of gene dosage; and 3) variations in the propensities of chemical reactions that have time-dependent reaction rates as a consequence of volume expansion and cell division. We give three biologically relevant examples to illustrate the use of our simulation tool in quantitative studies of systems biology and synthetic biology. PMID:23638057

Luo, Ruoyu; Ye, Lin; Tao, Chenyang; Wang, Kankan

2013-01-01

259

Toll-like receptor 9 gene polymorphism in chronic and aggressive periodontitis patients  

PubMed Central

Aim: Periodontitis is a multifactorial disease, with microbial dental plaque as the primary etiological factor. However, the manifestation and progression of periodontitis is influenced by a wide variety of other determinants and factors such as social and behavioral factors, systemic factors, microbial composition of dental plaque, genetic, and many other emerging risk factors. The aim of this study was to analyze genetic polymorphisms in the toll-like receptor 9 (TLR9) gene at - 1237C/T and its association with chronic and generalized aggressive periodontitis (GAgP) in an Indian population. Materials and Methods: This study was carried out on 90 subjects, which included 30 GAgP and 30 chronic periodontitis patients and 30 healthy controls. Within the limitations of our study, only 30 subjects were included in each group due to the low prevalence of GAgP patients. Blood samples were drawn from the subjects and analyzed for TLR9 genetic polymorphism at - 1237C/T by using polymerase chain reaction-restriction fragment length polymorphism method. Results: No significant difference was found in genotype and allele frequency of TLR9 genetic polymorphism (- 1237C/T) in generalized aggressive and chronic periodontitis patients and healthy controls. Conclusion: Toll-like receptor 9 genetic polymorphism at - 1237C/T may not be associated with GAgP and chronic periodontitis patients in Indian population. PMID:25624628

Ashok, Nipun; Warad, Shivaraj; Kalburgi, Nagaraj Balasaheb; Bilichodmath, Shivaprasad; Prabhakaran, Prabath Singh Valiyaparambil; Tarakji, Bassel

2014-01-01

260

Polymorphisms in the gene encoding estrogen receptor alpha are associated with osteoarthritis in Han Chinese women  

PubMed Central

Polymorphisms in the Xba I and Pvu II restriction enzyme recognition sites in the estrogen receptor-alpha gene (ESR1) have been associated with multiple diseases, including osteoarthritis. To determine whether such polymorphisms are associated with osteoarthritis in a Han Chinese population, 98 women with osteoarthritis and 196 healthy women were genotyped by PCR-RFLP of ESR1 with Xba I and Pvu II. Absence of a restriction polymorphism is indicated as an X or P allele; presence of the restriction polymorphism is indicated as an x or p allele. Clinical information was collected on each participant, including body weight, body mass index (BMI), knee radiograms, and bone mineral density (BMD). Body weight and BMI were higher for each Xba I genotype (all P < 0.05) in individuals with osteoarthritis compared to controls (p < 0.05). Femoral BMD was also significantly higher in the osteoarthritis group (p < 0.05). Additionally, the xx genotype for ESR1 was a significant risk factor for osteoarthritis (OR=1.98, 95% CI: 1.13~4.20, p=0.036). Thus, consistent with findings in other populations, the estrogen receptor genotype xx appears to be associated with susceptibility to osteoarthritis among Han Chinese women. PMID:25664105

Liu, Wei; Shao, Feng-Min; Yan, Lei; Cao, Hui-Xia; Qiu, Dong

2014-01-01

261

Investigation of Gamma-aminobutyric acid (GABA) A receptors genes and migraine susceptibility  

PubMed Central

Background Migraine is a neurological disorder characterized by recurrent attacks of severe headache, affecting around 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the number and type of genes involved is still unclear. Prior linkage studies have reported mapping of a migraine gene to chromosome Xq 24–28, a region containing a cluster of genes for GABA A receptors (GABRE, GABRA3, GABRQ), which are potential candidate genes for migraine. The GABA neurotransmitter has been implicated in migraine pathophysiology previously; however its exact role has not yet been established, although GABA receptors agonists have been the target of therapeutic developments. The aim of the present research is to investigate the role of the potential candidate genes reported on chromosome Xq 24–28 region in migraine susceptibility. In this study, we have focused on the subunit GABA A receptors type ? (GABRE) and type ? (GABRQ) genes and their involvement in migraine. Methods We have performed an association analysis in a large population of case-controls (275 unrelated Caucasian migraineurs versus 275 controls) examining a set of 3 single nucleotide polymorphisms (SNPs) in the coding region (exons 3, 5 and 9) of the GABRE gene and also the I478F coding variant of the GABRQ gene. Results Our study did not show any association between the examined SNPs in our test population (P > 0.05). Conclusion Although these particular GABA receptor genes did not show positive association, further studies are necessary to consider the role of other GABA receptor genes in migraine susceptibility. PMID:19087248

Fernandez, Francesca; Esposito, Teresa; Lea, Rod A; Colson, Natalie J; Ciccodicola, Alfredo; Gianfrancesco, Fernando; Griffiths, Lyn R

2008-01-01

262

Activation of tachykinin Neurokinin 3 receptors affects chromatin structure and gene expression by means of histone acetylation  

PubMed Central

The tachykinin, neurokinin 3 receptor (NK3R) is a g-protein coupled receptor that is broadly distributed in the nervous system and exerts its diverse physiological actions through multiple signaling pathways. Despite the role of the receptor system in a range of biological functions, the effects of NK3R activation on chromatin dynamics and gene expression have received limited attention. The present work determined the effects of senktide, a selective NK3R agonist, on chromatin organization, acetylation, and gene expression, using qRT-PCR, in a hypothalamic cell line (CLU 209) that expresses the NK3R. Senktide (1 nM, 10 nM) caused a relaxation of chromatin, an increase in global acetylation of histone H3 and H4, and an increase in the expression of a common set of genes involved in cell signaling, cell growth, and synaptic plasticity. Pretreatment with histone acetyltransferase (HAT) inhibitor (Garcinol and 2-methylene y-butylactone), that inhibits p300, p300/CREB Binding Protein (CBP) associated factor (PCAF), and GCN 5, prevented the senktide-induced increase in expression of most, but not all, of the genes upregulated in response to 1 nM and 10 nM senktide. Treatment with 100 nM had the opposite effect: a reduction in chromatin relaxation and decreased acetylation. The expression of four genes was significantly decreased and the HAT inhibitor had a limited effect in blocking the upregulation of genes in response to 100 nM senktide. Activation of the NK3R appears to recruit multiple pathways, including acetylation, and possibly histone deactylases, histone methylases, or DNA methylases to affect chromatin structure and gene expression. PMID:22985858

Thakar, Amit; Sylar, Elise; Flynn, Francis W.

2012-01-01

263

Activation of tachykinin, neurokinin 3 receptors affects chromatin structure and gene expression by means of histone acetylation.  

PubMed

The tachykinin, neurokinin 3 receptor (NK3R) is a g-protein coupled receptor that is broadly distributed in the nervous system and exerts its diverse physiological actions through multiple signaling pathways. Despite the role of the receptor system in a range of biological functions, the effects of NK3R activation on chromatin dynamics and gene expression have received limited attention. The present work determined the effects of senktide, a selective NK3R agonist, on chromatin organization, acetylation, and gene expression, using qRT-PCR, in a hypothalamic cell line (CLU 209) that expresses the NK3R. Senktide (1 nM, 10nM) caused a relaxation of chromatin, an increase in global acetylation of histone H3 and H4, and an increase in the expression of a common set of genes involved in cell signaling, cell growth, and synaptic plasticity. Pretreatment with histone acetyltransferase (HAT) inhibitor (garcinol and 2-methylene y-butylactone), that inhibits p300, p300/CREB binding protein (CBP) associated factor (PCAF), and GCN 5, prevented the senktide-induced increase in expression of most, but not all, of the genes upregulated in response to 1 nM and 10nM senktide. Treatment with 100 nM had the opposite effect: a reduction in chromatin relaxation and decreased acetylation. The expression of four genes was significantly decreased and the HAT inhibitor had a limited effect in blocking the upregulation of genes in response to 100 nM senktide. Activation of the NK3R appears to recruit multiple pathways, including acetylation, and possibly histone deactylases, histone methylases, or DNA methylases to affect chromatin structure and gene expression. PMID:22985858

Thakar, Amit; Sylar, Elise; Flynn, Francis W

2012-12-01

264

NR4A nuclear receptors mediate carnitine palmitoyltransferase 1A gene expression by the rexinoid HX600  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer The function of RXR heterodimers with NR4 receptors remains unknown. Black-Right-Pointing-Pointer The RXR ligand HX600 induces expression of carnitine palmitoyltransferase 1A (CPT1A). Black-Right-Pointing-Pointer HX600-induced CPT1A expression is mediated by the NR4 receptors, Nur77 and NURR1. Black-Right-Pointing-Pointer CPT1A induction by HX600 is not mediated by de novo protein synthesis. Black-Right-Pointing-Pointer CPT1A could be a target of the Nur77-RXR and NURR1-RXR heterodimers. -- Abstract: Retinoid X receptors (RXRs) are members of the nuclear receptor superfamily and can be activated by 9-cis retinoic acid (9CRA). RXRs form homodimers and heterodimers with other nuclear receptors such as the retinoic acid receptor and NR4 subfamily nuclear receptors, Nur77 and NURR1. Potential physiological roles of the Nur77-RXR and NURR1-RXR heterodimers have not been elucidated. In this study, we identified a gene regulated by these heterodimers utilizing HX600, a selective RXR agonist for Nur77-RXR and NURR1-RXR. While 9CRA induced many genes, including RAR-target genes, HX600 effectively induced only carnitine palmitoyltransferase 1A (CPT1A) in human teratocarcinoma NT2/D1 cells, which express RXR{alpha}, Nur77 and NURR1. HX600 also increased CPT1A expression in human embryonic kidney (HEK) 293 cells and hepatocyte-derived HepG2 cells. Although HX600 induced CPT1A less effectively than 9CRA, overexpression of Nur77 or NURR1 increased the HX600 response to levels similar to 9CRA in NT2/D1 and HEK293 cells. A dominant-negative form of Nur77 or NURR1 repressed the induction of CPT1A by HX600. A protein synthesis inhibitor did not alter HX600-dependent CPT1A induction. Thus, the rexinoid HX600 directly induces expression of CPT1A through a Nur77 or NURR1-mediated mechanism. CPT1A, a gene involved in fatty acid {beta}-oxidation, could be a target of RXR-NR4 receptor heterodimers.

Ishizawa, Michiyasu [Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610 (Japan)] [Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610 (Japan); Kagechika, Hiroyuki [Graduate School of Biomedical Science, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan)] [Graduate School of Biomedical Science, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Makishima, Makoto, E-mail: makishima.makoto@nihon-u.ac.jp [Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610 (Japan)] [Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610 (Japan)

2012-02-24

265

Two genetic loci participate in the regulation by iron of the gene for the human transferrin receptor  

SciTech Connect

Iron regulation of the human transferrin receptor gene was examined in murine cells transformed with chimeric constructs containing the human transferrin receptor gene's promoter and either the structural gene for bacterial chloramphenicol acetyltransferase or the human transferrin receptor cDNA. The activity of the transferrin receptor gene's promoter with the heterologous indicator gene was found to be {approx}3-fold higher in cells treated with the iron chelator desferrioxamine than in cells treated with the iron source, hemin. A higher degree of iron regulation was seen in the expression of the human transferrin receptor cDNA driven by its own promoter. The receptor cDNA under the control of the simian virus 40 early promoter was also iron-regulated. Several human transferrin receptor transcripts differing in their 3{prime} end were produced in the murine cells regardless of the promoter used, with the shorter transcripts being relatively unregulated by iron. Deletion of cDNA corresponding to most of the 3{prime} untranslated portion of the mRNA for the receptor ablated the iron regulation. The authors conclude that at least two genetic elements exist for the regulation of the transferrin receptor gene by iron. One has its locus in the DNA upstream of the transferrin receptor gene's transcription start site, and the other is dependent upon the integrity of the sequences in the 3{prime} end of the gene.

Casey, J.L.; Di Jeso, B.; Rao, K.; Klausner, R.D.; Harford, J.B. (National Institutes of Health, Bethesda, MD (USA))

1988-03-01

266

Global Renal Gene Expression Profiling Analysis in B2-Kinin Receptor Null Mice: Impact of Diabetes  

PubMed Central

Diabetic nephropathy (DN), the leading cause of end-stage renal failure, is clinically manifested by albuminuria and a progressive decline in glomerular filtration rate. The risk factors and mechanisms that contribute to the development and progression of DN are still incompletely defined. To address the involvement of bradykinin B2-receptors (B2R) in DN, we used a genome wide approach to study the effects of diabetes on differential renal gene expression profile in wild type and B2R knockout (B2R?/?) mice. Diabetes was induced with streptozotocin and plasma glucose levels and albumin excretion rate (AER) were measured at predetermined times throughout the 23 week study period. Longitudinal analysis of AER indicated that diabetic B2R?/?D null mice had a significantly decreased AER levels compared to wild type B2R+/+D mice (P?=?0.0005). Results from the global microarray study comparing gene expression profiles among four groups of mice respectively: (B2R+/+C, B2R+/+D, B2R?/?C and B2R?/?D) highlighted the role of several altered pathological pathways in response to disruption of B2R and to the diabetic state that included: endothelial injury, oxidative stress, insulin and lipid metabolism and inflammatory process with a marked alteration in the pro-apoptotic genes. The findings of the present study provide a global genomics view of biomarkers that highlight the mechanisms and putative pathways involved in DN. PMID:23028588

Jaffa, Miran A.; Kobeissy, Firas; Al Hariri, Moustafa; Chalhoub, Hussein; Eid, Assaad; Ziyadeh, Fuad N.; Jaffa, Ayad A.

2012-01-01

267

Zinc finger transcription factor Slug is a novel target gene of aryl hydrocarbon receptor  

SciTech Connect

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor. We previously showed that AhR localizes predominantly in the cytoplasm under high cell densities of a keratinocytes cell line, HaCaT, but accumulates in the nucleus at low cell densities. In the current report, we show that the Slug, which is a member of the snail/slug family of zinc finger transcriptional repressors critical for induction of epithelial-mesenchymal transitions (EMT), is activated transcriptionally in accordance with nuclear accumulation of AhR. By reporter assay of the promoter of the Slug gene, gel shift and chromatin immunoprecipitation analyses showed AhR directly binds to xenobiotic responsive element 5 at - 0.7 kb of the gene. AhR-targeted gene silencing by small interfering RNA duplexes led to the abolishment of not only CYP1A1 but also Slug induction by 3-methycholanthrene. The Slug was co-localized to the AhR at the wound margins of HaCaT cells, where apparent nuclear distribution of AhR and Slug was observed. The induced Slug was associated with reduction of an epithelial marker of cytokeratin-18 and with an increase in the mesenchymal marker, fibronectin. Taken together, these findings suggest that AhR participated in Slug induction, which, in turn, regulates cellular physiology including cell adhesion and migration.

Ikuta, Togo [Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan); Kawajiri, Kaname [Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan) and Solution Oriented Research for Science and Technology (SORST), Japan Science and Technology Agency, 4-1-8 Honmachi, Kawaguchi, Saitama 331-0012 (Japan)]. E-mail: kawajiri@cancer-c.pref.saitama.jp

2006-11-01

268

Erythropoietin (EPO) Increases Myelin Gene Expression in CG4 Oligodendrocyte Cells through the Classical EPO Receptor  

PubMed Central

Erythropoietin (EPO) has protective effects in neurodegenerative and neuroinflammatory diseases, including in animal models of multiple sclerosis, where EPO decreases disease severity. EPO also promotes neurogenesis and is protective in models of toxic demyelination. In this study, we asked whether EPO could promote neurorepair by also inducing remyelination. In addition, we investigated whether the effect of EPO could be mediated by the classical erythropoietic EPO receptor (EPOR), since it is still questioned if EPOR is functional in nonhematopoietic cells. Using CG4 cells, a line of rat oligodendrocyte precursor cells, we found that EPO increases the expression of myelin genes (myelin oligodendrocyte glycoprotein [MOG] and myelin basic protein [MBP]). EPO had no effect in wild-type CG4 cells, which do not express EPOR, whereas it increased MOG and MBP expression in cells engineered to overexpress EPOR (CG4-EPOR). This was reflected in a marked increase in MOG protein levels, as detected by Western blot. In these cells, EPO induced by 10-fold the early growth response gene 2 (Egr2), which is required for peripheral myelination. However, Egr2 silencing with a siRNA did not reverse the effect of EPO, indicating that EPO acts through other pathways. In conclusion, EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR. This study demonstrates that EPOR can mediate neuroreparative effects. PMID:23821361

Cervellini, Ilaria; Annenkov, Alexander; Brenton, Thomas; Chernajovsky, Yuti; Ghezzi, Pietro; Mengozzi, Manuela

2013-01-01

269

Common variation in the fibroblast growth factor receptor 2 gene is not associated with endometriosis risk  

PubMed Central

BACKGROUND Endometriosis is a polygenic disease with a complex and multifactorial aetiology that affects 8–10% of women of reproductive age. Epidemiological data support a link between endometriosis and cancers of the reproductive tract. Fibroblast growth factor receptor 2 (FGFR2) has recently been implicated in both endometrial and breast cancer. Our previous studies on endometriosis identified significant linkage to a novel susceptibility locus on chromosome 10q26 and the FGFR2 gene maps within this linkage region. We therefore hypothesized that variation in FGFR2 may contribute to the risk of endometriosis. METHODS We genotyped 13 single nucleotide polymorphisms (SNPs) densely covering a 27 kb region within intron 2 of FGFR2 including two SNPs (rs2981582 and rs1219648) significantly associated with breast cancer and a total 40 tagSNPs across 150 kb of the FGFR2 gene. SNPs were genotyped in 958 endometriosis cases and 959 unrelated controls. RESULTS We found no evidence for association between endometriosis and FGFR2 intron 2 SNPs or SNP haplotypes and no evidence for association between endometriosis and variation across the FGFR2 gene. CONCLUSIONS Common variation in the breast-cancer implicated intron 2 and other highly plausible causative candidate regions of FGFR2 do not appear to be a major contributor to endometriosis susceptibility in our large Australian sample. PMID:18285324

Zhao, Zhen Zhen; Pollock, Pamela M.; Thomas, Shane; Treloar, Susan A.; Nyholt, Dale R.; Montgomery, Grant W.

2008-01-01

270

Mutation analysis of androgen receptor gene: multiple uses for a single test.  

PubMed

Androgen receptor gene mutations are one of the leading causes of disorders of sex development (DSD) exhibited by sexual ambiguity or sex reversal. In this study, 2 families with patients whom diagnosed clinically as androgen insensitivity syndrome (AIS) were physically and genetically examined. This evaluation carried out by cytogenetic and molecular analysis including karyotype and sequencing of SRY and AR genes. In family 1, two brothers and their mother were hemizygous and heterozygous respectively for c.2522G>A variant, while one of their healthy brother was a completely normal hemizygote. Family 2 assessment demonstrated the c.639G>A (rs6152) mutation in two siblings who were reared as girls. The SRY gene was intact in all of the study's participants. Our findings in family 1 could be a further proof for the pathogenicity of the c.2522G>A variant. Given the importance of AR mutations in development of problems such as sex assignment in AIS patients, definitive diagnosis and phenotype-genotype correlation could be achieved by molecular genetic tests that in turn could have promising impacts in clinical management and also in prenatal diagnosis of prospect offspring. In this regard, phenotype-genotype correlation could be helpful and achieved by molecular genetic tests. This could influence the clinical management of the patients as well as prenatal diagnosis for the prospective offspring. PMID:25241384

Shojaei, Azadeh; Behjati, Farkhondeh; Ebrahimzadeh-Vesal, Reza; Razzaghy-Azar, Maryam; Derakhshandeh-Peykar, Pupak; Izadi, Pantea; Kajbafzadeh, Abdol-Mohammad; Dowlatih, Mohammad-Ali; Karami, Fatemeh; Tavakkoly-Bazzaz, Javad

2014-12-01

271

Episodic Positive Selection in the Evolution of Avian Toll-Like Receptor Innate Immunity Genes  

PubMed Central

Toll-like receptors (TLRs) are a family of conserved pattern-recognition molecules responsible for initiating innate and acquired immune responses. Because they play a key role in host defence, these genes have received increasing interest in the evolutionary and population genetics literature, as their variation represents a potential target of adaptive evolution. However, the role of pathogen-mediated selection (i.e. episodic positive selection) in the evolution of these genes remains poorly known and has not been examined outside of mammals. A recent increase in the number of bird species for which TLR sequences are available has enabled us to examine the selective processes that have influenced evolution of the 10 known avian TLR genes. Specifically, we tested for episodic positive selection to identify codons that experience purifying selection for the majority of their evolution, interspersed with bursts of positive selection that may occur only in restricted lineages. We included up to 23 species per gene (mean?=?16.0) and observed that, although purifying selection was evident, an average of 4.5% of codons experienced episodic positive selection across all loci. For four genes in which sequence coverage traversed both the extracellular leucine-rich repeat region (LRR) and transmembrane/intracellular domains of the proteins, increased positive selection was observed at the extracellular domain, consistent with theoretical predictions. Our results provide evidence that episodic positive selection has played an important role in the evolution of most avian TLRs, consistent with the role of these loci in pathogen recognition and a mechanism of host-pathogen coevolution. PMID:24595315

Grueber, Catherine E.; Wallis, Graham P.; Jamieson, Ian G.

2014-01-01

272

Thyroid hormone receptor regulates most genes independently of fibroblast growth factor 21 in liver.  

PubMed

Thyroid hormone (TH) acts through specific receptors (TRs), which are conditional transcription factors, to induce fibroblast growth factor 21 (FGF21), a peptide hormone that is usually induced by fasting and that influences lipid and carbohydrate metabolism via local hepatic and systemic endocrine effects. While TH and FGF21 display overlapping actions when administered, including reductions in serum lipids, according to the current models these hormones act independently in vivo. In this study, we examined mechanisms of regulation of FGF21 expression by TH and tested the possibility that FGF21 is required for induction of hepatic TH-responsive genes. We confirm that active TH (triiodothyronine (T3)) and the TR?-selective thyromimetic GC1 increase FGF21 transcript and peptide levels in mouse liver and that this effect requires TR?. T3 also induces FGF21 in cultured hepatocytes and this effect involves direct actions of TR?1, which binds a TRE within intron 2 of FGF21. Gene expression profiles of WT and Fgf21-knockout mice are very similar, indicating that FGF21 is dispensable for the majority of hepatic T3 gene responses. A small subset of genes displays diminished T3 response in the absence of FGF21. However, most of these are not obviously directly involved in T3-dependent hepatic metabolic processes. Consistent with these results, T3-dependent effects on serum cholesterol are maintained in the Fgf21(-/-) background and we observe no effect of the Fgf21-knockout background on serum triglycerides and glucose. Our findings indicate that T3 regulates the genes involved in classical hepatic metabolic responses independently of FGF21. PMID:25501997

Zhang, Aijun; Sieglaff, Douglas H; York, Jean Philippe; Suh, Ji Ho; Ayers, Stephen D; Winnier, Glenn E; Kharitonenkov, Alexei; Pin, Christopher; Zhang, Pumin; Webb, Paul; Xia, Xuefeng

2015-03-01

273

Interleukin 2 (IL-2) augments transcription of the IL-2 receptor gene.  

PubMed Central

We demonstrate that purified interleukin 2 (IL-2) can directly upregulate IL-2 receptor expression on phytohemagglutinin-activated T lymphocytes maintained in culture until IL-2 receptor expression had markedly declined. The IL-2-induced increase in IL-2 receptor number is maximal within 12 hr, requires new RNA and protein synthesis, and is mediated by an interaction of ligand with the high-affinity receptors for IL-2. IL-2 stimulation results in increased accumulation of IL-2 receptor mRNA within 4 hr, while an increase in IL-2 receptor gene transcription is detected within 30 min in isolated nuclei. In addition, IL-2 incubation results in increased amounts of c-myc and transferrin receptor mRNA, but it does not augment levels of mRNA encoding the beta chain of the T-cell receptor for antigen. These results demonstrate that IL-2 can directly upregulate transcription and expression of its own receptor and, therefore, indicate that IL-2 may regulate IL-2-dependent immune responses, in part, by influencing the expression of IL-2 receptors. Images PMID:2987968

Depper, J M; Leonard, W J; Drogula, C; Krönke, M; Waldmann, T A; Greene, W C

1985-01-01

274

Gene expression of vasoactive intestinal peptide receptors in human lung cancer.  

PubMed

Despite significant improvement in the diagnosis and treatment of various human carcinomas, the 5-year survival rate for lung cancer remains below 20%. Vasoactive intestinal peptide (VIP) is an important neuropeptide in the control of lung physiology, and exerts its functions mainly through two receptor subtypes, VPAC1 and VPAC2. Receptors for VPAC1 and VPAC2 are present in human lung cancer cells, but very limited information exists about the mRNA expression of these VIP receptor subtypes in lung cancer specimens. The aim of the present study was to investigate by RT-PCR the mRNA expression of the VPAC1 and VPAC2 receptors in surgical specimens of 43 human lung cancer specimens and 7 normal lung samples. mRNA expression of the VPAC1 receptor was detected in 51% of the tumor specimens, while the incidence of mRNA expression for VPAC2 was 46%. Twenty-one percent of the tumor samples expressed only the VPAC1 receptor and 16% displayed only the VPAC2 receptor, while 13 samples (30%) expressed neither subtype. Thirteen cancer tissue specimens (30%), expressed both of these VIP receptor subtypes. Three normal lung tissue specimens also displayed gene expression for VPAC1 and/or VPAC2 receptors. Our results support the additional investigation of the role of VIP and its receptors in human lung cancer and suggest a further development of VIP analogs for therapeutic and imaging purposes in this malignancy. PMID:21769421

Szilasi, Maria; Buglyo, Armin; Treszl, Andrea; Kiss, Lili; Schally, Andrew V; Halmos, Gabor

2011-10-01

275

A common polymorphism in the LDL receptor gene has multiple effects on LDL receptor function.  

PubMed

A common synonymous single nucleotide polymorphism in exon 12 of the low-density lipoprotein receptor (LDLR) gene, rs688, has been associated with increased plasma total and LDL cholesterol in several populations. Using immortalized lymphoblastoid cell lines from a healthy study population, we confirmed an earlier report that the minor allele of rs688 is associated with increased exon 12 alternative splicing (P < 0.05) and showed that this triggered nonsense-mediated decay (NMD) of the alternatively spliced LDLR mRNA. However, since synonymous single nucleotide polymorphisms may influence structure and function of the encoded proteins by co-translational effects, we sought to test whether rs688 was also functional in the full-length mRNA. In HepG2 cells expressing LDLR cDNA constructs engineered to contain the major or minor allele of rs688, the latter was associated with a smaller amount of LDLR protein at the cell surface (-21.8 ± 0.6%, P = 0.012), a higher amount in the lysosome fraction (+25.7 ± 0.3%, P = 0.037) and reduced uptake of fluorescently labeled LDL (-24.3 ± 0.7%, P < 0.01). Moreover, in the presence of exogenous proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces cellular LDL uptake by promoting lysosomal degradation of LDLR, the minor allele resulted in reduced capacity of a PCSK9 monoclonal antibody to increase LDL uptake. These findings are consistent with the hypothesis that rs688, which is located in the ?-propeller region of LDLR, has effects on LDLR activity beyond its role in alternative splicing due to impairment of LDLR endosomal recycling and/or PCSK9 binding, processes in which the ?-propeller is critically involved. PMID:23297366

Gao, Feng; Ihn, Hansel E; Medina, Marisa W; Krauss, Ronald M

2013-04-01

276

Massive Losses of Taste Receptor Genes in Toothed and Baleen Whales  

PubMed Central

Taste receptor genes are functionally important in animals, with a surprising exception in the bottlenose dolphin, which shows extensive losses of sweet, umami, and bitter taste receptor genes. To examine the generality of taste gene loss, we examined seven toothed whales and five baleen whales and sequenced the complete repertoire of three sweet/umami (T1Rs) and ten bitter (T2Rs) taste receptor genes. We found all amplified T1Rs and T2Rs to be pseudogenes in all 12 whales, with a shared premature stop codon in 10 of the 13 genes, which demonstrated massive losses of taste receptor genes in the common ancestor of whales. Furthermore, we analyzed three genome sequences from two toothed whales and one baleen whale and found that the sour taste marker gene Pkd2l1 is a pseudogene, whereas the candidate salty taste receptor genes are intact and putatively functional. Additionally, we examined three genes that are responsible for taste signal transduction and found the relaxation of functional constraints on taste signaling pathways along the ancestral branch leading to whales. Together, our results strongly suggest extensive losses of sweet, umami, bitter, and sour tastes in whales, and the relaxation of taste function most likely arose in the common ancestor of whales between 36 and 53 Ma. Therefore, whales represent the first animal group to lack four of five primary tastes, probably driven by the marine environment with high concentration of sodium, the feeding behavior of swallowing prey whole, and the dietary switch from plants to meat in the whale ancestor. PMID:24803572

Feng, Ping; Zheng, Jinsong; Rossiter, Stephen J.; Wang, Ding; Zhao, Huabin

2014-01-01

277

The ERBB3 receptor in cancer and cancer gene therapy  

Microsoft Academic Search

ERBB3, a member of the epidermal growth factor receptor (EGFR) family, is unique in that its tyrosine kinase domain is functionally defective. It is activated by neuregulins, by other ERBB and nonERBB receptors as well as by other kinases, and by novel mechanisms. Downstream it interacts prominently with the phosphoinositol 3-kinase\\/AKT survival\\/mitogenic pathway, but also with GRB, SHC, SRC, ABL,

G Sithanandam; L M Anderson

2008-01-01

278

Interleukin 1 receptor antagonist gene polymorphism association with lichen sclerosus  

Microsoft Academic Search

Cytokines play key roles in immune responses, inflammation and fibrosis. The balance between levels of cytokines, their receptors and specific inhibitors controls inflammatory reactions in tissues. The pathogenesis of lichen sclerosus is unknown but probably involves cytokine mediators such as interleukin 1 (IL-1) and interleukin 1 receptor antagonist (IL-1ra). The IL-1ra is a competitive inhibitor of IL-1a and IL-1ß, and

Frances E. Clay; Michael J. Cork; Joanna K. Tarlow; Alexandra I. F. Blakemore; Christine I. Harrington; Fiona Lewis; Gordon W. Duff

1994-01-01

279

Comparative genomic analysis reveals independent expansion of a lineage-specific gene family in vertebrates: The class II cytokine receptors and their ligands in mammals and fish  

PubMed Central

Background The high degree of sequence conservation between coding regions in fish and mammals can be exploited to identify genes in mammalian genomes by comparison with the sequence of similar genes in fish. Conversely, experimentally characterized mammalian genes may be used to annotate fish genomes. However, gene families that escape this principle include the rapidly diverging cytokines that regulate the immune system, and their receptors. A classic example is the class II helical cytokines (HCII) including type I, type II and lambda interferons, IL10 related cytokines (IL10, IL19, IL20, IL22, IL24 and IL26) and their receptors (HCRII). Despite the report of a near complete pufferfish (Takifugu rubripes) genome sequence, these genes remain undescribed in fish. Results We have used an original strategy based both on conserved amino acid sequence and gene structure to identify HCII and HCRII in the genome of another pufferfish, Tetraodon nigroviridis that is amenable to laboratory experiments. The 15 genes that were identified are highly divergent and include a single interferon molecule, three IL10 related cytokines and their potential receptors together with two Tissue Factor (TF). Some of these genes form tandem clusters on the Tetraodon genome. Their expression pattern was determined in different tissues. Most importantly, Tetraodon interferon was identified and we show that the recombinant protein can induce antiviral MX gene expression in Tetraodon primary kidney cells. Similar results were obtained in Zebrafish which has 7 MX genes. Conclusion We propose a scheme for the evolution of HCII and their receptors during the radiation of bony vertebrates and suggest that the diversification that played an important role in the fine-tuning of the ancestral mechanism for host defense against infections probably followed different pathways in amniotes and fish. PMID:12869211

Lutfalla, Georges; Crollius, Hugues Roest; Stange-thomann, Nicole; Jaillon, Olivier; Mogensen, Knud; Monneron, Danièle

2003-01-01

280

Occurrence of a Salmonella enterica Serovar Typhimurium DT104-Like Antibiotic Resistance Gene Cluster Including the floR Gene in S. enterica Serovar Agona  

PubMed Central

Recently a chromosomal locus possibly specific for Salmonella enterica serovar Typhimurium DT104 has been reported that contains a multiple antibiotic resistance gene cluster. Evidence is provided that Salmonella enterica serovar Agona strains isolated from poultry harbor a similar gene cluster including the newly described floR gene, conferring cross-resistance to chloramphenicol and florfenicol. PMID:10770778

Cloeckaert, Axel; Sidi Boumedine, Karim; Flaujac, Geraldine; Imberechts, Hein; D'Hooghe, Inge; Chaslus-Dancla, Elisabeth

2000-01-01

281

Non-Synonymous Single Nucleotide Polymorphisms in the P2X Receptor Genes: Association with Diseases, Impact on Receptor Functions and Potential Use as Diagnosis Biomarkers  

PubMed Central

P2X receptors are Ca2+-permeable cationic channels in the cell membranes, where they play an important role in mediating a diversity of physiological and pathophysiological functions of extracellular ATP. Mammalian cells express seven P2X receptor genes. Single nucleotide polymorphisms (SNPs) are widespread in the P2RX genes encoding the human P2X receptors, particularly the human P2X7 receptor. This article will provide an overview of the non-synonymous SNPs (NS-SNPs) that have been associated with or implicated in altering the susceptibility to pathologies or disease conditions, and discuss the consequences of the mutations resulting from such NS-SNPs on the receptor functions. Disease-associated NS-SNPs in the P2RX genes have been valuable in understanding the disease etiology and the receptor function, and are promising as biomarkers to be used for the diagnosis and development of stratified therapeutics. PMID:25079442

Caseley, Emily A.; Muench, Stephen P.; Roger, Sebastien; Mao, Hong-Ju; Baldwin, Stephen A.; Jiang, Lin-Hua

2014-01-01

282

Abstract The Wnt family includes a number of genes, such as wingless (wg), which encode secreted glycopro-  

E-print Network

Abstract The Wnt family includes a number of genes, such as wingless (wg), which encode secreted Introduction The Wnt family includes a number of secreted glycopro- teins that function as signaling molecules in numerous developmental processes. For example, the Drosophila wg gene, a Wnt family member, is required

Patel, Nipam H.

283

Identification of Gene Markers for Activation of the Nuclear Receptor Pregnane X Receptor  

EPA Science Inventory

Many environmentally-relevant chemicals and drugs activate the nuclear receptor pregnane X receptor (PXR). Activation of PXR in the mouse liver can lead to increases in liver weight in part through increased hepatocyte replication similar to chemicals that activate other nuclear ...

284

Polymorphisms of the vitamin D receptor gene and stress fractures.  

PubMed

Our aim was to evaluate the association between VDR polymorphisms and calcaneal Stiffness Index (SI) with stress fractures in a case control study including male military personnel. Thirty- two patients with stress fractures were matched with 32 uninjured healthy volunteers (controls), by gender, age, height, body weight, and level of physical activity. The two groups were genotyped for the FokI, BsmI, ApaI, and TaqI polymorphisms of the VDR gene with PCR-RFLP method. In addition, calcaneal SI was measured by heel quantitative ultrasound in both groups. Data were analyzed by chi-squared test and logistic regression analysis. The f allele was significantly more frequent in patients than in controls (p=0.013), while the B allele showed such a tendency without reaching statistical significance (p=0.052). Among the entire cohort, a 2.7-fold and a 2.0-fold increase in risk of stress fractures was associated with the f and B alleles (OR, 2.7, 95% CI, 1.2-5.9; p=0.014 and OR, 2.0, 95% CI, 1.0-4.1; p=0.053, respectively). No statistically significant association was found between the incidence of stress fractures and t or a alleles. Decreased T-scores were also associated with the presence of f and B alleles. Mean values of T-scores of SI were statistically significantly lower in patients than in controls (p=0.018). These results suggest that the FokI and BsmI polymorphisms of the VDR gene could be associated with increased risk of stress fractures among military personnel. Moreover, a low calcaneal SI could represent a measurable index of this increased risk. PMID:19391078

Chatzipapas, C; Boikos, S; Drosos, G I; Kazakos, K; Tripsianis, G; Serbis, A; Stergiopoulos, S; Tilkeridis, C; Verettas, D-A; Stratakis, C A

2009-08-01

285

Polymorphisms of the Vitamin D Receptor Gene and Stress Fractures  

PubMed Central

Our aim was to evaluate the association between VDR polymorphisms and calcaneal Stiffness Index (SI) with stress fractures in a case control study including male military personnel. Thirty- two patients with stress fractures were matched with 32 uninjured healthy volunteers (controls), by gender, age, height, body weight, and level of physical activity. The two groups were genotyped for the FokI, BsmI, ApaI, and TaqI polymorphisms of the VDR gene with PCR-RFLP method. In addition, calcaneal SI was measured by heel quantitative ultrasound in both groups. Data were analyzed by chi-squared test and logistic regression analysis. The f allele was significantly more frequent in patients than in controls (p=0.013), while the B allele showed such a tendency without reaching statistical significance (p=0.052). Among the entire cohort, a 2.7-fold and a 2.0-fold increase in risk of stress fractures was associated with the f and B alleles (OR, 2.7, 95% CI, 1.2–5.9; p=0.014 and OR, 2.0, 95% CI, 1.0–4.1; p=0.053, respectively). No statistically significant association was found between the incidence of stress fractures and t or a alleles. Decreased T-scores were also associated with the presence of f and B alleles. Mean values of T-scores of SI were statistically significantly lower in patients than in controls (p=0.018). These results suggest that the FokI and BsmI polymorphisms of the VDR gene could be associated with increased risk of stress fractures among military personnel. Moreover, a low calcaneal SI could represent a measurable index of this increased risk. PMID:19391078

Chatzipapas, C.; Boikos, S.; Drosos, G. I.; Kazakos, K.; Tripsianis, G.; Serbis, A.; Stergiopoulos, S.; Tilkeridis, C.; Verettas, D.-A.; Stratakis, C. A.

2011-01-01

286

Global Footprints of Purifying Selection on Toll-Like Receptor Genes Primarily Associated with Response to Bacterial Infections in Humans  

PubMed Central

Toll-like receptors (TLRs) are directly involved in host–pathogen interactions. Polymorphisms in these genes are associated with susceptibility to infectious diseases. To understand the influence of environment and pathogen diversity on the evolution of TLR genes, we have undertaken a large-scale population-genetic study. Our study included two hunter–gatherer tribal populations and one urbanized nontribal population from India with distinct ethnicities (n = 266) and 14 populations inhabiting four different continents (n = 1,092). From the data on DNA sequences of cell-surface TLR genes, we observed an excess of rare variants and a large number of low frequency haplotypes in each gene. Nonsynonymous changes were few in every population and the commonly used statistical tests for detecting natural selection provided evidence of purifying selection. The evidence of purifying selection acting on the cell-surface TLRs of the innate immune system is not consistent with Haldane’s theory of coevolution of immunity genes, at least of innate immunity genes, with pathogens. Our study provides evidence that genes of the cell-surface TLRs, that is, TLR2 and TLR4, have been so optimized to defend the host against microbial infections that new mutations in these genes are quickly eliminated. PMID:24554585

Mukherjee, Souvik; Ganguli, Debdutta; Majumder, Partha P.

2014-01-01

287

Association between vitamin D receptor gene polymorphisms and chronic periodontitis among Libyans  

PubMed Central

Background Chronic periodontitis (CP) is a common oral disease characterized by inflammation in the supporting tissue of the teeth ‘the periodontium’, periodontal attachment loss, and alveolar bone loss. The disease has a microbial etiology; however, recent findings suggest that the genetic factors, such as vitamin D receptor (VDR) gene polymorphisms, have also been included. Aim Investigation of the relationship between VDR gene polymorphisms and CP among Libyans. Materials and methods In this study, we examined 196 unrelated Libyans between the ages of 25 and 65 years, including 99 patients and 97 controls. An oral examination based on Ramfjord Index was performed at different dental clinics in Tripoli and information were collected using a self-reported questionnaire. DNA was extracted from buccal swabs; the VDR ApaI, BsmI, and FokI polymorphisms were genotyped using polymerase chain reaction and were sequenced using Sanger Method. Results A significant difference in the newly detected ApaI SNP C/T rs#731236 was found (p=0.022), whereas no significant differences were found in ApaI SNP G/T rs#7975232, BsmI SNP A/G rs#1544410, and FokI SNP A/G rs#2228570 between patients and controls (p=0.939, 0.466, 0.239), respectively. Conclusion VDR ApaI SNP C/T rs#731236 may be related to the risk of CP in the Libyan population. PMID:25795245

El Jilani, Mouna M.; Mohamed, Abdenaser A.; Zeglam, Hamza Ben; Alhudiri, Inas M.; Ramadan, Ahmad M.; Saleh, Saleh S.; Elkabir, Mohamed; Amer, Ibrahim Ben; Ashammakhi, Nureddin; Enattah, Nabil S.

2015-01-01

288

A single-vector EYFP reporter gene assay for G protein-coupled receptors.  

PubMed

We here present an improved and simplified assay to study signal transduction of the Gs class of G protein-coupled receptors (GPCRs). The assay is based on a single plasmid combining the genes for any Gs protein-coupled GPCR and the cAMP response element-related expression of enhanced yellow fluorescent protein. On transfection, stable human embryonic kidney 293 (HEK293) cell lines presented high assay sensitivity and an unprecedented signal-to-noise ratio of up to 300, even in the absence of trichostatin A. The robustness of the assay was demonstrated through the cloning of reporter gene cell lines with melanocortin 4 receptor (MC4R), the human type I pituitary adenylate cyclase-activating polypeptide receptor (hPAC1), and the two vasoactive intestinal peptide receptors (VPAC1 and VPAC2). PMID:25681566

Hald, Helle; Wu, Boqian; Bouakaz, Lamine; Meldal, Morten

2015-05-01

289

An extended gene protein/products boolean network model including post-transcriptional regulation  

PubMed Central

Background Networks Biology allows the study of complex interactions between biological systems using formal, well structured, and computationally friendly models. Several different network models can be created, depending on the type of interactions that need to be investigated. Gene Regulatory Networks (GRN) are an effective model commonly used to study the complex regulatory mechanisms of a cell. Unfortunately, given their intrinsic complexity and non discrete nature, the computational study of realistic-sized complex GRNs requires some abstractions. Boolean Networks (BNs), for example, are a reliable model that can be used to represent networks where the possible state of a node is a boolean value (0 or 1). Despite this strong simplification, BNs have been used to study both structural and dynamic properties of real as well as randomly generated GRNs. Results In this paper we show how it is possible to include the post-transcriptional regulation mechanism (a key process mediated by small non-coding RNA molecules like the miRNAs) into the BN model of a GRN. The enhanced BN model is implemented in a software toolkit (EBNT) that allows to analyze boolean GRNs from both a structural and a dynamic point of view. The open-source toolkit is compatible with available visualization tools like Cytoscape and allows to run detailed analysis of the network topology as well as of its attractors, trajectories, and state-space. In the paper, a small GRN built around the mTOR gene is used to demonstrate the main capabilities of the toolkit. Conclusions The extended model proposed in this paper opens new opportunities in the study of gene regulation. Several of the successful researches done with the support of BN to understand high-level characteristics of regulatory networks, can now be improved to better understand the role of post-transcriptional regulation for example as a network-wide noise-reduction or stabilization mechanisms. PMID:25080304

2014-01-01

290

Aryl hydrocarbon receptor SNP -130 C/T associates with dioxins susceptibility through regulating its receptor activity and downstream effectors including interleukin 24.  

PubMed

Dioxins are persistent environmental pollutants that cause multiple adverse health effects in humans, mainly through binding to the ligand-activated transcription factor, aryl hydrocarbon receptor (AhR). Genetic variation in AhR may modulate the susceptibility to dioxins. In this study, we aimed to evaluate the effects of the single nucleotide polymorphism (SNP) -130 C/T in the AhR promoter on dioxin-inducible gene transcription, and to investigate interleukin-24 (IL-24) and interleukin-1? (IL-1?) as proxies for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure. Using primary human chorionic stromal cells, we found that cells with the TT genotype showed higher AhR mRNA and protein levels than did those of the CC genotype. Microarray was carried out to analyze the gene expression profiles of cells (CC and TT genotype) after exposing the cells to TCDD. Several genes associated with human disorders were more highly up-regulated in cells of the TT genotype. Higher up-regulation of IL-24 and IL-1? mRNA in cells with the TT genotype was observed. Furthermore, blood samples from 64 Yusho patients who were accidentally exposed to high concentrations of dioxins were analyzed for the genotype, dioxins concentrations and serum levels of IL-24 and IL-1?. We observed higher serum IL-24 levels and lower serum IL-1? levels in Yusho patients with the TT genotype than in those with the CC genotype. AhR SNP -130 C/T affects serum IL-24 and IL-1? levels, independently of serum dioxins concentrations in Yusho patients. Our observations demonstrate that SNP -130 C/T modulates AhR expression and expression levels of IL-24 and IL-1?, and suggest an association of AhR SNP -130 C/T with the susceptibility to dioxins. PMID:25445724

Liu, Ge; Asanoma, Kazuo; Takao, Tomoka; Tsukimori, Kiyomi; Uchi, Hiroshi; Furue, Masutaka; Kato, Kiyoko; Wake, Norio

2015-01-22

291

SUPERFAMILY 1.75 including a domain-centric gene ontology method  

PubMed Central

The SUPERFAMILY resource provides protein domain assignments at the structural classification of protein (SCOP) superfamily level for over 1400 completely sequenced genomes, over 120 metagenomes and other gene collections such as UniProt. All models and assignments are available to browse and download at http://supfam.org. A new hidden Markov model library based on SCOP 1.75 has been created and a previously ignored class of SCOP, coiled coils, is now included. Our scoring component now uses HMMER3, which is in orders of magnitude faster and produces superior results. A cloud-based pipeline was implemented and is publicly available at Amazon web services elastic computer cloud. The SUPERFAMILY reference tree of life has been improved allowing the user to highlight a chosen superfamily, family or domain architecture on the tree of life. The most significant advance in SUPERFAMILY is that now it contains a domain-based gene ontology (GO) at the superfamily and family levels. A new methodology was developed to ensure a high quality GO annotation. The new methodology is general purpose and has been used to produce domain-based phenotypic ontologies in addition to GO. PMID:21062816

de Lima Morais, David A.; Fang, Hai; Rackham, Owen J. L.; Wilson, Derek; Pethica, Ralph; Chothia, Cyrus; Gough, Julian

2011-01-01

292

Gonadal sex differentiation in chicken embryos: Expression of estrogen receptor and aromatase genes  

Microsoft Academic Search

Estrogen is implicated in sexual differentiation of the avian gonad. Expression of the estrogen receptor and aromatase genes was therefore examined at the time of gonadal sex differentiation in chicken embryos, using reverse transcription and the polymerase chain reaction (RT-PCR). Estrogen receptor (cER) transcripts were detected in the gonads of both presumptive sexes at embryonic days 4.5, 5.5 and 6.5,

Craig A. Smith; Jane E. Andrews; Andrew H. Sinclair

1997-01-01

293

A screen of candidate genes and influence of ? 2-adrenergic receptor genotypes in postural tachycardia syndrome  

Microsoft Academic Search

ObjectiveTo screen candidate genes, encoding ?2-adrenergic receptor (?2AR), ?2C-adrenergic receptor (?2CAR), norepinephrine transporter (NET), and mitochondrial complex I (COI), for common single nucleotide polymorphisms (SNPs) in patients with postural tachycardia syndrome (POTS); alterations could potentially cause or aggravate orthostatic tachycardia and to relate ?2AR SNPs, known to effect venomotor tone, to heart rate (HR) and blood pressure measurements during 10-min

Kim K. Nickander; Paula J. Carlson; Raul A. Urrutia; Michael Camilleri; Phillip A. Low

2005-01-01

294

Molecular characterization of a mouse prostaglandin D receptor and functional expression of the cloned gene.  

PubMed Central

Prostanoid receptors belong to the family of G protein-coupled receptors with seven transmembrane domains. By taking advantage of nucleotide sequence homology among the prostanoid receptors, we have isolated and identified a cDNA fragment and its gene encoding a mouse prostaglandin (PG) D receptor by reverse transcription polymerase chain reaction and gene cloning. This gene codes for a polypeptide of 357 amino acids, with a calculated molecular weight of 40,012. The deduced amino acid sequence has a high degree of similarity with the mouse PGI receptor and the EP2 subtype of the PGE receptor, which together form a subgroup of the prostanoid receptors. Chinese hamster ovary cells stably expressing the gene showed a single class of binding sites for [#H]PGD2 with a Kd of 40 nM. This binding was displaced by unlabeled ligands in the following order: PGD2 > BW 245C (a PGD agonist) > BW A868C (a PGD antagonist) > STA2 (a thromboxane A2 agonist). PGE2, PGF2 alpha, and iloprost showed little displacement activity at concentrations up to 10 microM. PGD2 and BW 245C also increased cAMP levels in Chinese hamster ovary cells expressing the receptor, in a concentration-dependent manner. BW A868C showed a partial agonist activity in the cAMP assay. Northern blotting analysis with mouse poly(A)+ RNA identified a major mRNA species of 3.5 kb that was most abundantly expressed in the ileum, followed by lung, stomach, and uterus. Images PMID:7972033

Hirata, M; Kakizuka, A; Aizawa, M; Ushikubi, F; Narumiya, S

1994-01-01

295

T-cell enumeration from dried blood spots by quantifying rearranged T-cell receptor-? genes  

PubMed Central

Significant hurdles remain to large-scale implementation of medical interventions in the developing world due to the lack of a modern diagnostic infrastructure. This is especially pertinent to the international roll-out of antiretroviral drugs to treat HIV, which ideally includes a CD4 t-cell to determine eligibility. We designed a novel technique to estimate mature t-cell numbers by calculating the amount of rearranged t-cell receptor ? genes from dried blood spots of HIV-infected individuals in the United States and Uganda. It was observed that the rearranged t-cell receptor ? count correlated well with total lymphocyte counts from both study populations (Baltimore R=0.602, Uganda R=0.497; p<0.001) and the ability for this measurement to determine antiretroviral initiation was similar to total lymphocyte counts, which can be used to determine eligibility in HIV+ children. This technique as well as other dried blood spot based technologies could increase the diagnostic and monitoring capabilities in resource-limited settings. PMID:20109463

Redd, Andrew D; Ciccone, Emily J; Nakigozi, Gertrude; Keruly, Jeanne C; Ndyanabo, Anthony; Iga, Boaz; Gray, Ronald H; Serwadda, David; Quinn, Thomas C

2010-01-01

296

Oxytocin receptor gene variation predicts empathic concern and autonomic arousal while perceiving harm to others  

PubMed Central

Recent research indicates that the neuropeptide oxytocin and the gene for the oxytocin receptor (OXTR) have been implicated in the modulation of various social behaviors, including those related to empathy and sensitivity to others. In this study, we examine the hypothesis that genetic variation in OXTR is associated with autonomic reactions when perceiving others in distress. We also explore the possibility that individual disposition in empathic concern would differ by OXTR genotype. To address these questions, fifty-one male participants (18–35 years of age), genotyped for OXTR rs53576, viewed a social interaction containing high levels of individual distress and apparent physical pain. Electrodermal activity, a measure of sympathetic nervous system activity, was collected during the presentation of the stimuli. Participants also completed a self-report dispositional measure of empathy prior to starting the study and provided ratings of arousal while viewing the stimuli. OXTR variant rs53576 GG individuals showed increased levels of sympathetic and subjective arousal in response to the stimuli compared to A allele carriers. GG homozygotes also expressed greater levels of empathic concern. These findings support the importance of the oxytocin receptor variation in emotional and physiological reactions to the experiences of other conspecifics. PMID:24295535

Norman, Greg J.; Connelly, Jessica J.; Decety, Jean

2014-01-01

297

Association of Neurotensin receptor 1 gene polymorphisms with processing speed in healthy Chinese-Han subjects.  

PubMed

Neurotensin modulates dopamine and serotonin transmission in the brain. The study investigated whether genetic polymorphisms in the Neurotensin receptor 1 gene were associated with performance on processing speed and executive function. A total of 129 healthy Chinese-Han volunteers were recruited. Genotyping for three SNPs, including rs6090453, rs6011914, and rs2427422, was analyzed by using a PCR and a restriction fragment length polymorphism analysis. Performances of processing speed and executive function were assessed by using Trail Making Test-A (TMT-A), Wisconsin Card Sorting Test, and Stroop Color-Word Test. We found significant differences in the outcomes of TMT-A score among rs6090453C/G (F(2,126)=4.405, P=0.014) and rs2427422A/G (F(2,126)=7.498, P=0.001) genotypes. Neurotensin receptor 1 SNP polymorphisms were significantly associated with the variance in processing speed performance in a sample of Chinese college students. PMID:25159184

Wang, Man; Ma, Hui; Huang, Ying-lin; Zhu, Gang; Zhao, Jing-ping

2014-12-01

298

Regulation of human apolipoprotein m gene expression by orphan and ligand-dependent nuclear receptors.  

PubMed

Apolipoprotein M (apoM) plays an important role in the biogenesis and the metabolism of anti-atherogenic HDL particles in plasma and is expressed primarily in the liver and the kidney. We investigated the role of hormone nuclear receptors in apoM gene regulation in hepatic cells. Overexpression via adenovirus-mediated gene transfer and siRNA-mediated gene silencing established that hepatocyte nuclear factor 4 (HNF-4) is an important regulator of apoM gene transcription in hepatic cells. apoM promoter deletion analysis combined with DNA affinity precipitation and chromatin immunoprecipitation assays revealed that HNF-4 binds to a hormone-response element (HRE) in the proximal apoM promoter (nucleotides -33 to -21). Mutagenesis of this HRE decreased basal hepatic apoM promoter activity to 10% of control and abolished the HNF4-mediated transactivation of the apoM promoter. In addition to HNF-4, homodimers of retinoid X receptor and heterodimers of retinoid X receptor with receptors for retinoic acid, thyroid hormone, fibrates (peroxisome proliferator-activated receptor), and oxysterols (liver X receptor) were shown to bind with different affinities to the proximal HRE in vitro and in vivo. Ligands of these receptors strongly induced human apoM gene transcription and apoM promoter activity in HepG2 cells, whereas mutations in the proximal HRE abolished this induction. These findings provide novel insights into the role of apoM in the regulation of HDL by steroid hormones and into the development of novel HDL-based therapies for diseases such as diabetes, obesity, metabolic syndrome, and coronary artery disease that affect a large proportion of the population in Western countries. PMID:20660599

Mosialou, Ioanna; Zannis, Vassilis I; Kardassis, Dimitris

2010-10-01

299

Luciferase Reporter Gene Assay on Human 5-HT Receptor: Which Response Element Should Be Chosen?  

PubMed Central

Serotonin (5-HT) receptors are valuable molecular targets for antipsychotic drug discovery. Current reported methods for detecting 5-HT receptors, such as cAMP accumulation and calcium influx assay, are often demanding specialized instruments and inconvenient. The luciferase reporter gene assay, based on the responsible-element-regulated expression of luciferase, has been widely applied in the high-throughput functional assay for many targets because of its high sensitivity and reliability. However, 5-HT receptors couple to multiple G-proteins regulate respective downstream signalling pathways and are usually detected using different response elements. Hence, finding a suitable response element to fulfil the detection of different 5-HT receptors and make the results of luciferase reporter gene assays generalizable is very useful for active compounds screening. Here, we conducted three luciferase reporter assays using CRE, NFAT, and SRE response elements attached to 5-HT to detect the activation of different 5-HT receptors in CHO-K1 cells. The potencies and efficacies of the reported ligands (agonists and antagonists) were determined and compared. Our results indicate that CRE-luciferase reporter gene is sensitive and reliable to detect the activities of G protein-coupled 5-HT receptors. PMID:25622827

Chen, Yiming; Xu, Zhongyu; Wu, Dang; Li, Jian; Song, Cheng; Lu, Weiqiang; Huang, Jin

2015-01-01

300

De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies.  

PubMed

Emerging evidence indicates that epileptic encephalopathies are genetically highly heterogeneous, underscoring the need for large cohorts of well-characterized individuals to further define the genetic landscape. Through a collaboration between two consortia (EuroEPINOMICS and Epi4K/EPGP), we analyzed exome-sequencing data of 356 trios with the "classical" epileptic encephalopathies, infantile spasms and Lennox Gastaut syndrome, including 264 trios previously analyzed by the Epi4K/EPGP consortium. In this expanded cohort, we find 429 de novo mutations, including de novo mutations in DNM1 in five individuals and de novo mutations in GABBR2, FASN, and RYR3 in two individuals each. Unlike previous studies, this cohort is sufficiently large to show a significant excess of de novo mutations in epileptic encephalopathy probands compared to the general population using a likelihood analysis (p = 8.2 × 10(-4)), supporting a prominent role for de novo mutations in epileptic encephalopathies. We bring statistical evidence that mutations in DNM1 cause epileptic encephalopathy, find suggestive evidence for a role of three additional genes, and show that at least 12% of analyzed individuals have an identifiable causal de novo mutation. Strikingly, 75% of mutations in these probands are predicted to disrupt a protein involved in regulating synaptic transmission, and there is a significant enrichment of de novo mutations in genes in this pathway in the entire cohort as well. These findings emphasize an important role for synaptic dysregulation in epileptic encephalopathies, above and beyond that caused by ion channel dysfunction. PMID:25262651

2014-10-01

301

De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies  

PubMed Central

Emerging evidence indicates that epileptic encephalopathies are genetically highly heterogeneous, underscoring the need for large cohorts of well-characterized individuals to further define the genetic landscape. Through a collaboration between two consortia (EuroEPINOMICS and Epi4K/EPGP), we analyzed exome-sequencing data of 356 trios with the “classical” epileptic encephalopathies, infantile spasms and Lennox Gastaut syndrome, including 264 trios previously analyzed by the Epi4K/EPGP consortium. In this expanded cohort, we find 429 de novo mutations, including de novo mutations in DNM1 in five individuals and de novo mutations in GABBR2, FASN, and RYR3 in two individuals each. Unlike previous studies, this cohort is sufficiently large to show a significant excess of de novo mutations in epileptic encephalopathy probands compared to the general population using a likelihood analysis (p = 8.2 × 10?4), supporting a prominent role for de novo mutations in epileptic encephalopathies. We bring statistical evidence that mutations in DNM1 cause epileptic encephalopathy, find suggestive evidence for a role of three additional genes, and show that at least 12% of analyzed individuals have an identifiable causal de novo mutation. Strikingly, 75% of mutations in these probands are predicted to disrupt a protein involved in regulating synaptic transmission, and there is a significant enrichment of de novo mutations in genes in this pathway in the entire cohort as well. These findings emphasize an important role for synaptic dysregulation in epileptic encephalopathies, above and beyond that caused by ion channel dysfunction. PMID:25262651

Appenzeller, Silke; Balling, Rudi; Barisic, Nina; Baulac, Stéphanie; Caglayan, Hande; Craiu, Dana; De Jonghe, Peter; Depienne, Christel; Dimova, Petia; Djémié, Tania; Gormley, Padhraig; Guerrini, Renzo; Helbig, Ingo; Hjalgrim, Helle; Hoffman-Zacharska, Dorota; Jähn, Johanna; Klein, Karl Martin; Koeleman, Bobby; Komarek, Vladimir; Krause, Roland; Kuhlenbäumer, Gregor; Leguern, Eric; Lehesjoki, Anna-Elina; Lemke, Johannes R.; Lerche, Holger; Linnankivi, Tarja; Marini, Carla; May, Patrick; Møller, Rikke S.; Muhle, Hiltrud; Pal, Deb; Palotie, Aarno; Pendziwiat, Manuela; Robbiano, Angela; Roelens, Filip; Rosenow, Felix; Selmer, Kaja; Serratosa, Jose M.; Sisodiya, Sanjay; Stephani, Ulrich; Sterbova, Katalin; Striano, Pasquale; Suls, Arvid; Talvik, Tiina; von Spiczak, Sarah; Weber, Yvonne; Weckhuysen, Sarah; Zara, Federico; Abou-Khalil, Bassel; Alldredge, Brian K.; Andermann, Eva; Andermann, Frederick; Amron, Dina; Bautista, Jocelyn F.; Berkovic, Samuel F.; Bluvstein, Judith; Boro, Alex; Cascino, Gregory; Consalvo, Damian; Crumrine, Patricia; Devinsky, Orrin; Dlugos, Dennis; Epstein, Michael P.; Fiol, Miguel; Fountain, Nathan B.; French, Jacqueline; Friedman, Daniel; Geller, Eric B.; Glauser, Tracy; Glynn, Simon; Haas, Kevin; Haut, Sheryl R.; Hayward, Jean; Helmers, Sandra L.; Joshi, Sucheta; Kanner, Andres; Kirsch, Heidi E.; Knowlton, Robert C.; Kossoff, Eric H.; Kuperman, Rachel; Kuzniecky, Ruben; Lowenstein, Daniel H.; McGuire, Shannon M.; Motika, Paul V.; Novotny, Edward J.; Ottman, Ruth; Paolicchi, Juliann M.; Parent, Jack; Park, Kristen; Poduri, Annapurna; Sadleir, Lynette; Scheffer, Ingrid E.; Shellhaas, Renée A.; Sherr, Elliott; Shih, Jerry J.; Singh, Rani; Sirven, Joseph; Smith, Michael C.; Sullivan, Joe; Thio, Liu Lin; Venkat, Anu; Vining, Eileen P.G.; Von Allmen, Gretchen K.; Weisenberg, Judith L.; Widdess-Walsh, Peter; Winawer, Melodie R.; Allen, Andrew S.; Berkovic, Samuel F.; Cossette, Patrick; Delanty, Norman; Dlugos, Dennis; Eichler, Evan E.; Epstein, Michael P.; Glauser, Tracy; Goldstein, David B.; Han, Yujun; Heinzen, Erin L.; Johnson, Michael R.; Kuzniecky, Ruben; Lowenstein, Daniel H.; Marson, Anthony G.; Mefford, Heather C.; Nieh, Sahar Esmaeeli; O’Brien, Terence J.; Ottman, Ruth; Petrou, Stephen; Petrovski, Slavé; Poduri, Annapurna; Ruzzo, Elizabeth K.; Scheffer, Ingrid E.; Sherr, Elliott

2014-01-01

302

A specific gene conversion of an Alu family member in the LDL-receptor gene  

SciTech Connect

There are about 500,000 Alu family members dispersed throughout the human genome. Each of these elements is about 300 bp long and they are spread through an RNA-mediated transposition process termed retroposition. The Alu elements are not identical in sequence, but instead seem to be randomly diverged from several subfamily consensus sequences. These subfamilies can be roughly divided, based on diagnostic nucleotide positions, into groups of Alu sequences inserted during different stages in primate evolution. A PCR-based assay in which we amplify a specific Alu-containing site in the genomes of different primates allows us to detect the time of insertion of that individual Alu element in the primate genome. In studying members of one of the youngest Alu subfamilies, Sb2, we detected one element that had apparently inserted over 25 million years ago, much earlier than any other Sb2 element tested. Upon sequencing the amplified PCR products, we found that an Alu was in that precise location for 25 million years, but only in the human genome was it an Sb2 element. Its sequence was consistent with the oldest (PS) Alu subfamily in the other primates. This element evolves as expected throughout primates with the exception of the human, where it has suddenly acquired 16 separate diagnostic subfamily mutations. Although the exact mechanism is unknown, this Alu element has been specifically gene converted by an Alu element from this newer subfamily, without affecting the flanking sequences at all. It is clear that the majority of Alu subfamily evolution is dominated by insertion processes. However, this event shows that some of the details of Alu subfamily evolution may also be affected by gene conservation. Studies on several humans also show that this locus continued to accumulate mutations at an exceptionally high level after the conversion, making it useful as a polymorphic marker for the LDL-receptor locus.

Deininger, P.L.; Kass, D.H.; Batzer, M.A. [Lawrence Livermore National Lab., CA (United States)

1994-09-01

303

Cloning of thyroid hormone receptor genes expressed in metamorphosing flounder.  

PubMed

Two distinct cDNAs encoding thyroid hormone receptors (THRs) were cloned from a lambda gt10 library prepared from the whole bodies of metamorphosing flounder larvae (Paralichthys olivaceus). Deduced amino acid sequences of the two isolated cDNAs shared 96% and 92% homologies in their DNA- and hormone-binding domains, respectively. These were highly conserved when compared to THRs for other vertebrates: 88-96% in the DNA-binding domain and 84-94% in the hormone-binding domain. Other receptors in the nuclear receptor family showed lower homologies than those of THRs. Both THRs for the flounder had higher homologies with the alpha-type THRs of other vertebrates than with the beta-type. Thus, the two THRs for flounder were designated as fTHR alpha A and fTHR alpha B. PMID:7923940

Yamano, K; Araki, K; Sekikawa, K; Inui, Y

1994-01-01

304

Sequence variation in the androgen receptor gene is not a common determinant of male sexual orientation  

SciTech Connect

To test the hypothesis that DNA sequence variation in the androgen receptor gene plays a causal role in the development of male sexual orientation, the authors have (1) measured the degree of concordance of androgen receptor alleles in 36 pairs of homosexual brothers, (2) compared the lengths of polyglutamine and polyglycine tracts in the amino-terminal domain of the androgen receptor in a sample of 197 homosexual males and 213 unselected subjects, and (3) screened the entire androgen receptor coding region for sequence variation by PCR and denaturing gradient-gel electrophoresis (DGGE) and/or single-strand conformation polymorphism analysis in 20 homosexual males with homosexual or bisexual brothers and one homosexual male with no homosexual brothers, and screened the amino-terminal domain of the receptor for sequence variation in an additional 44 homosexual males, 37 of whom had one or more first- or second-degree male relatives who were either homosexual or bisexual. These analyses show that (1) homosexual brothers are as likely to be discordant as concordant for androgen receptor alleles; (2) there are no large-scale differences between the distributions of polyglycine or polyglutamine tract lengths in the homosexual and control groups; and (3) coding region sequence variation is not commonly found within the androgen receptor gene of homosexual men. The DGGE screen identified two rare amino acid substitutions, ser[sup 205] -to-arg and glu[sup 793]-to-asp, the biological significance of which is unknown. 32 refs., 2 figs., 2 tabs.

Macke, J.P.; Nathans, J.; King, V.L. (Johns Hopkins Univ., Baltimore, MD (United States)); Hu, N.; Hu, S.; Hamer, D.; Bailey, M. (Northwestern Univ., Evanston, IL (United States)); Brown, T. (Johns Hopkins Univ. School of Hygiene and Public Health, Baltimore, MD (United States))

1993-10-01

305

Effects of leptin and leptin receptor gene polymorphisms on lung cancer.  

PubMed

Leptin (LEP), an adipocyte-derived cytokine, has been reported to participate in carcinogenesis. Elevated levels of systemic and pulmonary LEP are associated with diseases related to lung injury and lung cancer. The purpose of the present study was to investigate if the LEP and leptin receptor (LEPR) gene polymorphisms are associated with lung cancer in a cohort of Turkish population. One hundred and sixty-two lung cancer patients and 130 healthy controls were included in the study. The genotypes of LEP gene -2548G?>?A and LEPR gene Q223R polymorphisms were determined using polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP) analysis. The genotype frequencies of LEP -2548G?>?A polymorphism showed statistically significant differences between lung cancer patients and controls (p?=?0.007). GA?+?AA genotypes and A allele of LEP -2548G?>?A polymorphism was found to be susceptibility factors for lung cancer (p?=?0.003, odds ratio (OR) 2.32, 95 % confidence interval (CI) 1.32-4.10; p?=?0.003, OR 1.65, 95 % CI 1.18-2.29, respectively). The genotype and allele frequencies of LEPR Q223R polymorphism did not show any statistically significant differences between lung cancer patients and controls (p?=?0.782 and p?=?0.762, respectively). Although AA-QQ and AA-QR combined genotypes of LEP -2548G?>?A-LEPR Q223R loci were significantly higher in lung cancer patients (p?=?0.020 and p?=?0.047, respectively), GG-QQ, GG-QR, and AA-RR combined genotypes were significantly higher in control group. As a result, susceptibility effects of LEP -2548G?>?A polymorphism alone or in combination with LEPR Q223R polymorphism on lung cancer were observed. Further studies are necessary to prove the association of LEP and LEPR gene polymorphisms with lung cancer. PMID:25027400

Unsal, Meftun; Kara, Nurten; Karakus, Nevin; Tural, Sengul; Elbistan, Mehmet

2014-10-01

306

Endothelial Protein C Receptor Gene Variants Not Associated with Severe Malaria in Ghanaian Children  

PubMed Central

Background Two recent reports have identified the Endothelial Protein C Receptor (EPCR) as a key molecule implicated in severe malaria pathology. First, it was shown that EPCR in the human microvasculature mediates sequestration of Plasmodium falciparum-infected erythrocytes. Second, microvascular thrombosis, one of the major processes causing cerebral malaria, was linked to a reduction in EPCR expression in cerebral endothelial layers. It was speculated that genetic variation affecting EPCR functionality could influence susceptibility to severe malaria phenotypes, rendering PROCR, the gene encoding EPCR, a promising candidate for an association study. Methods Here, we performed an association study including high-resolution variant discovery of rare and frequent genetic variants in the PROCR gene. The study group, which previously has proven to be a valuable tool for studying the genetics of malaria, comprised 1,905 severe malaria cases aged 1–156 months and 1,866 apparently healthy children aged 2–161 months from the Ashanti Region in Ghana, West Africa, where malaria is highly endemic. Association of genetic variation with severe malaria phenotypes was examined on the basis of single variants, reconstructed haplotypes, and rare variant analyses. Results A total of 41 genetic variants were detected in regulatory and coding regions of PROCR, 17 of which were previously unknown genetic variants. In association tests, none of the single variants, haplotypes or rare variants showed evidence for an association with severe malaria, cerebral malaria, or severe malaria anemia. Conclusion Here we present the first analysis of genetic variation in the PROCR gene in the context of severe malaria in African subjects and show that genetic variation in the PROCR gene in our study population does not influence susceptibility to major severe malaria phenotypes. PMID:25541704

Schuldt, Kathrin; Ehmen, Christa; Evans, Jennifer; May, Juergen; Ansong, Daniel; Sievertsen, Juergen; Muntau, Birgit; Ruge, Gerd; Agbenyega, Tsiri; Horstmann, Rolf D.

2014-01-01

307

Identification of Homeotic Target Genes in Drosophila Melanogaster Including Nervy, a Proto-Oncogene Homologue  

PubMed Central

In Drosophila, the specific morphological characteristics of each segment are determined by the homeotic genes that regulate the expression of downstream target genes. We used a subtractive hybridization procedure to isolate activated target genes of the homeotic gene Ultrabithorax (Ubx). In addition, we constructed a set of mutant genotypes that measures the regulatory contribution of individual homeotic genes to a complex target gene expression pattern. Using these mutants, we demonstrate that homeotic genes can regulate target gene expression at the start of gastrulation, suggesting a previously unknown role for the homeotic genes at this early stage. We also show that, in abdominal segments, the levels of expression for two target genes increase in response to high levels of Ubx, demonstrating that the normal down-regulation of Ubx in these segments is functional. Finally, the DNA sequence of cDNAs for one of these genes predicts a protein that is similar to a human proto-oncogene involved in acute myeloid leukemias. These results illustrate potentially general rules about the homeotic control of target gene expression and suggest that subtractive hybridization can be used to isolate interesting homeotic target genes. PMID:7498738

Feinstein, P. G.; Kornfeld, K.; Hogness, D. S.; Mann, R. S.

1995-01-01

308

The chromosomal localization of the human follicle-stimulating hormone receptor gene (FSHR) on 2p21-p16 ls similar to that of the luteinizing hormone receptor gene  

SciTech Connect

Two cDNA probes (5[prime]and 3[prime]region) corresponding to the human follicle-stimulating hormone receptor gene (FSHR) were used for chromosomal localization by in situ hybridization. The localization obtained on chromosome 2p21-p16 is similar to that of the luteinizing hormone/choriogonadotropin (LH/CG) receptor gene. 24 refs. 1 fig., 1 tab.

Rousseau-Merck, M.F.; Berger, R.; Atger, M.; Loosfelt, H.; Milgrom, E. (INSERM, Paris (France))

1993-01-01

309

Fracture, bone mineral density, and the effects of calcitonin receptor gene in postmenopausal Koreans  

Microsoft Academic Search

Summary  In a candidate gene association study, we found that the variations of calcitonin receptor (CALCR) gene were related to the risk of vertebral fracture and increased bone mineral density (BMD).\\u000a \\u000a \\u000a \\u000a \\u000a Introduction  Calcitonins through calcitonin receptors inhibit osteoclast-mediated bone resorption and modulate calcium ion excretion by\\u000a the kidney and also prevent vertebral bone loss in early menopause.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  To identify genetically susceptible factors

H.-J. Lee; S.-Y. Kim; G. S. Kim; J.-Y. Hwang; Y.-J. Kim; B. Jeong; T.-H. Kim; E. K. Park; S. H. Lee; H.-L. Kim; J.-M. Koh; J.-Y. Lee

2010-01-01

310

Gene structure of human cholecystokinin (CCK) type-A receptor: body fat content is related to CCK type-A receptor gene promoter polymorphism  

Microsoft Academic Search

The transcriptional start site of the human cholecystokinin (CCK)-A receptor gene was determined by the Capsite Hunting method. Two sequence changes were detected, a G to T change in nucleotide ?128, and an A to G change in nucleotide ?81. The homozygote (T\\/T, G\\/G) was detected in 25 of 1296 individuals (1.9%) in the cohort study. This polymorphism showed a

Akihiro Funakoshi; Kyoko Miyasaka; Hideo Matsumoto; Shunji Yamamori; Sohichi Takiguchi; Kazuhiro Kataoka; Yutaka Takata; Kimihiko Matsusue; Akira Kono; Hiroshi Shimokata

2000-01-01

311

THE ROLE OF ANDROGEN RECEPTOR IN TRANSCRIPTIONAL MODULATION OF CANNABINOID RECEPTOR TYPE 1 GENE IN RAT TRIGEMINAL GANGLIA  

PubMed Central

We have previously shown that anti-hyperalgesic effects of cannabinoid agonists under inflammatory condition are much greater in male than female, and that inflammatory cytokines upregulate cannabinoid receptor type 1 (CB1) expression in male, but not female, trigeminal ganglia (TG) in a testosterone-dependent manner. In this study, we investigated the mechanisms underlying the testosterone-mediated regulation of peripheral CB1 expression. We hypothesized that testosterone upregulates CB1 through transcriptional modulation by androgen receptor (AR). Interleukin-1 beta (IL-1?), a proinflammatory cytokine, upregulated CB1 mRNA expression in TG of male rats. The cytokine-induced upregulation was prevented by the pre-treatment with flutamide, a specific antagonist for AR, but not by ICI 182,780, a specific antagonist for estrogen receptor, suggesting that the effects of testosterone are not mediated by estradiol, a testosterone metabolite. The expression levels of AR and IL-1? receptors were comparable between male and female TG, suggesting that the male specific IL-1? effects on CB1 upregulation occurs downstream to these receptors. The chromatin immunoprecipitation assay showed AR binding to the CB1 promoter in the rat TG. Furthermore, luciferase reporter assay revealed that AR activated the CB1 gene in response to testosterone or dihydrotestosterone treatment. These experiments provided compelling evidence that testosterone regulates CB1 gene transcription in TG through AR following cytokine stimulation. These results should provide mechanistic bases for understanding cytokine–hormone–neuron interactions in peripheral cannabinoid systems, and have important clinical implications for pain patients in whom testosterone level is naturally low, gradually declining or pharmacologically compromised. PMID:24055403

LEE, K. S.; ASGAR, J.; ZHANG, Y.; CHUNG, M.-K.; RO, J. Y.

2013-01-01

312

The evolution of drug-activated nuclear receptors: one ancestral gene diverged into two xenosensor genes in mammals  

PubMed Central

Background Drugs and other xenobiotics alter gene expression of cytochromes P450 (CYP) by activating the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) in mammals. In non-mammalian species, only one xenosensor gene has been found. Using chicken as a model organism, the aim of our study was to elucidate whether non-mammalian species only have one or two xenosensors like mammals. Results To explore the evolutionary aspect of this divergence, we tried to identify additional xenobiotic sensing nuclear receptors in chicken using various experimental approaches. However, none of those revealed novel candidates. Ablation of chicken xenobiotic receptor (CXR) function by RNAi or dominant-negative alleles drastically reduced drug-induction in a chicken hepatoma cell line. Subsequently, we functionally and structurally characterized CXR and compared our results to PXR and CAR. Despite the high similarity in their amino acid sequence, PXR and CAR have very distinct modes of activation. Some aspects of CXR function, e.g. direct ligand activation and high promiscuity are very reminiscent of PXR. On the other hand, cellular localization studies revealed common characteristics of CXR and CAR in terms of cytoplasmic-nuclear distribution. Finally, CXR has unique properties regarding its regulation in comparison to PXR and CAR. Conclusion Our finding thus strongly suggest that CXR constitutes an ancestral gene which has evolved into PXR and CAR in mammals. Future studies should elucidate the reason for this divergence in mammalian versus non-mammalian species. PMID:15479477

Handschin, Christoph; Blättler, Sharon; Roth, Adrian; Looser, Renate; Oscarson, Mikael; Kaufmann, Michel R; Podvinec, Michael; Gnerre, Carmela; Meyer, Urs A

2004-01-01

313

Molecular map of Chromosome 19 including three genes affecting bleeding time: ep, ru , and bm  

Microsoft Academic Search

The mouse ruby eye (ru) and pale ear (ep) pigment dilution genes cause platelet storage pool deficiency (SPD) and prolonged bleeding times. The brachymorphic (bm) gene, in addition to causing skeletal abnormalities, is also associated with prolonged bleeding times. All three hemorrhagic genes are found within 10 cM on Chromosome (Chr) 19. In this study, 15 microsatellite markers and five

E. P. O'Brien; E. K. Novak; S. A. Keller; C. Poirier; J.-L. Guénet; R. T. Swank

1994-01-01

314

The Aryl Hydrocarbon Receptor Complex and the Control of Gene Expression  

PubMed Central

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that controls the expression of a diverse set of genes. The toxicity of the potent AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin is almost exclusively mediated through this receptor. However, the key alterations in gene expression that mediate toxicity are poorly understood. It has been established through characterization of AhR-null mice that the AhR has a required physiological function, yet how endogenous mediators regulate this orphan receptor remains to be established. A picture as to how the AhR/ARNT heterodimer actually mediates gene transcription is starting to emerge. The AhR/ARNT complex can alter transcription both by binding to its cognate response element and through tethering to other transcription factors. In addition, many of the coregulatory proteins necessary for AhR-mediated transcription have been identified. Cross talk between the estrogen receptor and the AhR at the promoter of target genes appears to be an important mode of regulation. Inflammatory signaling pathways and the AhR also appear to be another important site of cross talk at the level of transcription. A major focus of this review is to highlight experimental efforts to characterize nonclassical mechanisms of AhR-mediated modulation of gene transcription. PMID:18540824

Beischlag, Timothy V.; Morales, J. Luis; Hollingshead, Brett D.; Perdew, Gary H.

2008-01-01

315

Ecdysone Receptor-Based Gene Switches for Applications in Plants  

Technology Transfer Automated Retrieval System (TEKTRAN)

There are a number of circumstances in which it is advantageous to use an inducible gene regulation system, the most obvious being when introducing transgenes whose constitutive expression is detrimental or even lethal to the host plants. The selective induction of gene expression is typically accom...

316

The arthritis severity locus Cia5a regulates the expression of inflammatory mediators including Syk pathway genes and proteases in pristane-induced arthritis  

PubMed Central

Background Cia5a is a locus on rat chromosome 10 that regulates disease severity and joint damage in two models of rheumatoid arthritis, collagen- and pristane-induced arthritis (PIA). In this study, we aimed to identify cellular and molecular processes regulated by Cia5a using microarray-based gene expression analysis of synovial tissues from MHC identical DA (severe erosive disease) and DA.F344(Cia5a) congenics (mild non-erosive disease) rats. Results Synovial tissues from six DA and eight DA.F344(Cia5a) rats were analyzed 21 days after the induction of PIA using the Illumina RatRef-12 BeadChip (21,922 genes) and selected data confirmed with qPCR. There was a significantly increased expression of pro-inflammatory mediators such as Il1b (5-fold), Il18 (3.9-fold), Cxcl1 (10-fold), Cxcl13 (7.5-fold) and Ccl7 (7.9-fold), and proteases like Mmp3 (23-fold), Mmp9 (32-fold), Mmp14 (4.4-fold) and cathepsins in synovial tissues from DA, with reciprocally reduced levels in congenics. mRNA levels of 47 members of the Spleen Tyrosine Kinase (Syk) pathway were significantly increased in DA synovial tissues compared with DA.F344(Cia5a), and included Syk (5.4-fold), Syk-activating receptors and interacting proteins, and genes regulated by Syk such as NFkB, and NAPDH oxidase complex genes. Nuclear receptors (NR) such as Rxrg, Pparg and Rev-erba were increased in the protected congenics, and so was the anti-inflammatory NR-target gene Scd1 (54-fold increase). Tnn (72-fold decrease) was the gene most significantly increased in DA. Conclusions Analyses of gene expression in synovial tissues revealed that the arthritis severity locus Cia5a regulates the expression of key mediators of inflammation and joint damage, as well as the expression of members of the Syk pathway. This expression pattern correlates with disease severity and joint damage and along with the gene accounting for Cia5a could become a useful biomarker to identify patients at increased risk for severe and erosive disease. The identification of the gene accounting for Cia5a has the potential to generate a new and important target for therapy and prognosis. PMID:23249408

2012-01-01

317

Analysis of single-nucleotide polymorphisms in the interleukin-4 receptor gene for association with inflammatory bowel disease.  

PubMed

Genetic linkage analysis in families with multiple cases of inflammatory bowel disease (IBD) has mapped a gene which confers susceptibility to IBD to the pericentromeric region of chromosome 16 (IBD1). The linked region includes the interleukin(IL)-4 receptor gene (IL4R). Since IL-4 regulation and expression are abnormal in IBD, the IL4R gene is thus both a positional and functional candidate for IBD1. We screened the gene for single-nucleotide polymorphisms (SNPs) by fluorescent chemical cleavage analysis, and tested a subset of known and novel SNPs for allelic association with IBD in 355 families, which included 435 cases of Crohn's disease and 329 cases of ulcerative colitis. No association was observed between a haplotype of four SNPs (val50ile, gln576arg, A3044G, G3289A) and either the Crohn's disease or ulcerative colitis phenotypes using the transmission disequilibrium test. There was also no evidence for association when the four markers were analyzed individually. The results indicate that these variants are not significant genetic determinants of IBD, and that the IL4R gene is unlikely to be IBD1. Linkage disequilibrium analyses showed that the val50ile and gln576arg variants are in complete equilibrium with each other, although they are separated by only about 21 kilobases of genomic DNA. This suggests that a very dense SNP map may be required to exclude or detect disease associations with some candidate genes. PMID:10663555

Olavesen, M G; Hampe, J; Mirza, M M; Saiz, R; Lewis, C M; Bridger, S; Teare, D; Easton, D F; Herrmann, T; Scott, G; Hirst, J; Sanderson, J; Hodgson, S V; Lee, J; MacPherson, A; Schreiber, S; Lennard-Jones, J E; Curran, M E; Mathew, C G

2000-01-01

318

MAPPING OF TOLL LIKE RECEPTOR (TLR) GENES IN RAINBOW TROUT  

Technology Transfer Automated Retrieval System (TEKTRAN)

Toll-like receptors (TLRs) are a family of transmembrane proteins that recognize conserved pathogen structures to induce innate immune effector molecules. In vertebrates, TLRs can distinguish among classes of pathogens and serve an important role in orchestrating the appropriate adaptive immune resp...

319

An eight-gene molecular phylogeny of the Kickxellomycotina, including the first phylogenetic placement of Asellariales.  

PubMed

Kickxellomycotina is a recently described subphylum encompassing four zygomycete orders (Asellariales, Dimargaritales, Harpellales, Kickxellales). These fungi are united by the formation of disciform septal pores containing lenticular plugs. Morphological diversification and life history evolution has made the relationships within and among the four orders difficult to resolve on those grounds alone. Here we infer the phylogeny of the Kickxellomycotina based on an eight-gene supermatrix including both ribosomal rDNA (18S, 28S, 5.8S) and protein sequences (MCM7, TSR1, RPB1, RPB2, ?-tubulin). The results of this study demonstrate that Kickxellomycotina is monophyletic and related to members of the Zoopagomycotina. Eight unique clades are distinguished in the Kickxellomycotina, including the four defined orders (Asellariales, Dimargaritales, Harpellales, Kickxellales) as well as four genera previously placed within two of these orders (Barbatospora, Orphella, Ramicandelaber, Spiromyces). Dimargaritales and Ramicandelaber are the earliest diverging members of the subphylum, although the relationship between these taxa remains uncertain. The remaining six clades form a monophyletic group, with Barbatospora diverging first. The next split divides the remaining members of the subphylum into two subclades: (i) Asellariales and Harpellales and (ii) Kickxellales, Orphella and Spiromyces. Estimation of ancestral states for four potentially informative morphological and ecological characters reveals that arthropod endosymbiosis might have been an important factor in the early evolution of the Kickxellomycotina. PMID:24891422

Tretter, Eric D; Johnson, Eric M; Benny, Gerald L; Lichtwardt, Robert W; Wang, Yan; Kandel, Prasanna; Novak, Stephen J; Smith, James F; White, Merlin M

2014-01-01

320

Evidence for increased olfactory receptor gene repertoire size in two nocturnal bird species with well-developed olfactory ability  

Microsoft Academic Search

BACKGROUND: In vertebrates, the molecular basis of the sense of smell is encoded by members of a large gene family, namely olfactory receptor (OR) genes. Both the total number of OR genes and the proportion of intact OR genes in a genome may indicate the importance of the sense of smell for an animal. There is behavioral, physiological, and anatomical

Silke S Steiger; Andrew E Fidler; Bart Kempenaers

2009-01-01

321

Selective prostacyclin receptor agonism augments glucocorticoid-induced gene expression in human bronchial epithelial cells.  

PubMed

Prostacyclin receptor (IP-receptor) agonists display anti-inflammatory and antiviral activity in cell-based assays and in preclinical models of asthma and chronic obstructive pulmonary disease. In this study, we have extended these observations by demonstrating that IP-receptor activation also can enhance the ability of glucocorticoids to induce genes with anti-inflammatory activity. BEAS-2B bronchial epithelial cells stably transfected with a glucocorticoid response element (GRE) luciferase reporter were activated in a concentration-dependent manner by the glucocorticoid dexamethasone. An IP-receptor agonist, taprostene, increased cAMP in these cells and augmented luciferase expression at all concentrations of dexamethasone examined. Analysis of the concentration-response relationship that described this effect showed that taprostene increased the magnitude of transcription without affecting the potency of dexamethasone and was, thus, steroid-sparing in this simple system. RO3244794, an IP-receptor antagonist, and oligonucleotides that selectively silenced the IP-receptor gene, PTGIR, abolished these effects of taprostene. Infection of BEAS-2B GRE reporter cells with an adenovirus vector encoding a highly selective inhibitor of cAMP-dependent protein kinase (PKA) also prevented taprostene from enhancing GRE-dependent transcription. In BEAS-2B cells and primary cultures of human airway epithelial cells, taprostene and dexamethasone interacted either additively or cooperatively in the expression of three glucocorticoid-inducible genes (GILZ, MKP-1, and p57(kip2)) that have anti-inflammatory potential. Collectively, these data show that IP-receptor agonists can augment the ability of glucocorticoids to induce anti-inflammatory genes in human airway epithelial cells by activating a cAMP/PKA-dependent mechanism. This observation may have clinical relevance in the treatment of airway inflammatory diseases that are either refractory or respond suboptimally to glucocorticoids. PMID:19880449

Wilson, Sylvia M; Shen, Pamela; Rider, Christopher F; Traves, Suzanne L; Proud, David; Newton, Robert; Giembycz, Mark A

2009-11-15

322

Acetylcholine receptor subunit genes from Ancylostoma caninum: altered transcription patterns associated with pyrantel resistance.  

PubMed

The molecular mechanism of resistance to nicotinic agonist anthelmintics such as pyrantel and levamisole in nematodes of medical and veterinary significance is poorly understood. The identification of pyrantel-resistant isolates of the canine hookworm, Ancylostoma caninum, provides an opportunity to explore, at a molecular level, the mechanism of cholinergic resistance in a species that is a model for the human hookworms. Here we describe the cloning of three A. caninum genes orthologous to components of the pyrantel-sensitive nicotinic acetylcholine receptor in Caenorhabditis elegans (UNC-29, -38, -63). Analysis of mRNA levels by quantitative PCR was also performed on these genes, plus an additional three nicotinic acetylcholine receptor subunit genes thought not to be constituents of the pyrantel-sensitive receptor, for which a partial sequence was obtained. Gene sequences and mRNA levels were compared between two isolates of A. caninum showing either high- or low-level resistance to pyrantel (as shown previously by in vivo efficacy and in vitro comparative studies). While no polymorphisms of likely significance between the two A. caninum isolates were observed, quantitative analysis of transcription revealed significantly lower levels for the three putative pyrantel receptor subunits (AAR-29, -38 and -63) in the highly pyrantel-resistant isolate compared with the isolate with low-level resistance. In contrast, transcription of the three subunits thought not to constitute the pyrantel receptor (AAR-8, -15 and -19) was either not significantly different between the two isolates, or slightly higher in the highly-resistant isolate. This data suggests that reduced transcription of the mRNA coding for nicotinic acetylcholine receptor subunits that form the pyrantel-sensitive receptors may be a component of the pyrantel resistance mechanism in A. caninum. PMID:18823982

Kopp, Steven R; Coleman, Glen T; Traub, Rebecca J; McCarthy, James S; Kotze, Andrew C

2009-03-01

323

Identification of small molecule antagonists of the human mas-related gene-X1 receptor.  

PubMed

The recently identified mas-related-gene (MRG) family of receptors, located primarily in sensory neurons of the dorsal root ganglion, has been implicated in the perception of pain. Thus, antagonists of this class of receptors have been postulated to be useful analgesics. Toward this end, we developed a cell-based beta-lactamase (BLA) reporter gene assay to identify small molecule antagonists of the human MRG-X1 receptor from a library of compounds. Single-cell clones expressing functional receptors were selected using the BLA reporter gene technology. The EC50 for the MRG agonist peptide, BAM15, appeared to be comparable between the BLA assay and the intracellular Ca2+ transient assays in these cells. Ultra high-throughput screening of approximately 1 million compounds in a 1.8-microl cell-based BLA reporter gene assay was conducted in a 3456-well plate format. Compounds exhibiting potential antagonist profile in the BLA assay were confirmed in the second messenger Ca2+ transient assay. A cell-based receptor trafficking assay was used to further validate the mechanism of action of these compounds. Several classes of compounds, particularly the 2,3-disubstituted azabicyclo-octanes, appear to be relatively potent antagonists at the human MRG-X1 receptors, as confirmed by the receptor trafficking assay and radioligand binding studies. Furthermore, the structure-activity relationship reveals that within this class of compounds, the diphenylmethyl moiety is constant at the 2-substituent, whereas the 3-substituent is directly correlated with the antagonist activity of the compound. PMID:16510108

Kunapuli, Priya; Lee, Seungtaek; Zheng, Wei; Alberts, Melissa; Kornienko, Oleg; Mull, Rebecca; Kreamer, Anthony; Hwang, Jong-Ik; Simon, Melvin I; Strulovici, Berta

2006-04-01

324

Genetic basis of endocrine disease 4: The spectrum of mutations in the androgen receptor gene that causes androgen resistance  

SciTech Connect

Mutations in the androgen receptor gene cause phenotypic abnormalities of male sexual development that range from a female phenotype (complete testicular feminization) to that of undervirilized or infertile men. Using the tools of molecular biology, the authors have analyzed androgen receptor gene mutations in 31 unrelated subjects with androgen resistance syndromes. Most of the defects are due to nucleotide changes that cause premature termination codons or single amino acid substitutions within the open reading frame encoding the androgen receptor, and the majority of these substitutions are localized in three regions of the androgen receptor: the DNA-binding domain and two segments of the androgen-binding domain. Less frequently, partial or complete gene deletions have been identified. Functional studies and immunoblot assays of the androgen receptors in patients with androgen resistance indicate that in most cases the phenotypic abnormalities are the result of impairment of receptor function or decreases in receptor abundance or both. 34 refs., 2 figs.

McPhaul, M.J.; Marcelli, M.; Zoppi, S.; Griffin, J.E.; Wilson, J.D. (Univ. of Texas Southwestern Medical Center, Dallas (United States))

1993-01-01

325

Improvement of a Monopartite Ecdysone Receptor Gene Switch and Demonstration of its Utility in Regulation of Transgene Expression in Plants  

Technology Transfer Automated Retrieval System (TEKTRAN)

Chemical inducible gene regulation systems provide essential tools for the precise regulation of transgene expression in plants and animals. We have recent developed a two-hybrid ecdysone receptor (EcR) gene regulation system that works in conjunction with the retinoid X receptor of Locusta migrato...

326

Peroxisome Proliferator-activated Receptor ? Stimulation of Adipocyte ApoE Gene Transcription Mediated by the Liver Receptor X Pathway*  

PubMed Central

Peroxisome proliferator-activated receptor (PPAR?) agonists increase insulin sensitivity in humans and are useful for treating human diabetes. Treatment with these agonists leads to increased apoE expression and triglyceride accumulation in adipocytes. The importance of apoE for adipocyte triglyceride accumulation is demonstrated by observations that triglyceride accumulation is impaired in apoE knockout adipocytes treated with PPAR? agonists. The current studies investigate the molecular mechanism for PPAR? stimulation of the adipocyte apoE gene and demonstrate that the liver receptor X (LXR) response element within an apoE gene downstream enhancer is required for the apoE response to PPAR? agonists. The response of the apoE gene to treatment with PPAR? agonists was delayed beyond 12 h suggesting the involvement of an intermediary pathway. The combined addition of PPAR? and LXR agonists did not increase apoE response beyond that observed with addition of either alone. Deletion or mutation of the LXR response element completely eliminated the adipocyte apoE gene response to a PPAR? agonist. Chromatin immunoprecipitation analyses performed using isolated adipocytes, or adipose tissue from mice treated with PPAR? agonists, showed increased LXR binding to the apoE gene after PPAR? agonist treatment. Knockdown of LXR expression completely eliminated the increase in apoE message, protein, and triglyceride in response to PPAR? stimulation. The LXR response element has been previously shown to mediate sterol responsiveness of the apoE gene, and apoE expression plays an important role in adipocyte triglyceride balance. The current observations suggest that the PPAR?-LXR-apoE regulatory cascade could be an important molecular link for cross-talk between adipocyte triglyceride and cholesterol homeostasis. PMID:19218241

Yue, Lili; Mazzone, Theodore

2009-01-01

327

Low-density lipoprotein receptor gene familial hypercholesterolemia variant database: update and pathological assessment.  

PubMed

Familial hypercholesterolemia (FH) is caused predominately by variants in the low-density lipoprotein receptor gene (LDLR). We report here an update of the UCL LDLR variant database to include variants reported in the literature and in-house between 2008 and 2010, transfer of the database to LOVDv.2.0 platform (https://grenada.lumc.nl/LOVD2/UCL-Heart/home.php?select_db=LDLR) and pathogenicity analysis. The database now contains over 1288 different variants reported in FH patients: 55% exonic substitutions, 22% exonic small rearrangements (<100 bp), 11% large rearrangements (>100 bp), 2% promoter variants, 10% intronic variants and 1 variant in the 3' untranslated sequence. The distribution and type of newly reported variants closely matches that of the 2008 database, and we have used these variants (n= 223) as a representative sample to assess the utility of standard open access software (PolyPhen, SIFT, refined SIFT, Neural Network Splice Site Prediction Tool, SplicePort and NetGene2) and additional analyses (Single Amino Acid Polymorphism database, analysis of conservation and structure and Mutation Taster) for pathogenicity prediction. In combination, these techniques have enabled us to assign with confidence pathogenic predictions to 8/8 in-frame small rearrangements and 8/9 missense substitutions with previously discordant results from PolyPhen and SIFT analysis. Overall, we conclude that 79% of the reported variants are likely to be disease causing. PMID:22881376

Usifo, Ebele; Leigh, Sarah E A; Whittall, Ros A; Lench, Nicholas; Taylor, Alison; Yeats, Corin; Orengo, Christine A; Martin, Andrew C R; Celli, Jacopo; Humphries, Steve E

2012-09-01

328

Regulation of Antigen Receptor Gene Assembly by Genetic-Epigenetic Crosstalk  

PubMed Central

Many aspects of gene function are coordinated by changes in the epigenome, which include dynamic revisions of chromatin modifications, genome packaging, subnuclear localization, and chromosome conformation. All of these mechanisms are used by developing lymphocytes to regulate the assembly of functional antigen receptor genes by V(D)J recombination. This somatic rearrangement of the genome must be tightly regulated to ensure proper B and T cell development and to avoid chromosomal translocations that cause lymphoid tumors. V(D)J recombination is controlled by a complex interplay between cis-acting regulatory elements that use transcription factors as liaisons to communicate with epigenetic pathways. Genetic-epigenetic crosstalk is a key strategy employed by precursor lymphocytes to modulate chromatin configurations at Ig and Tcr loci and thereby permit or deny access to a single V(D)J recombinase complex. This article describes our current knowledge of how genetic elements orchestrate crosstalk with epigenetic mechanisms to regulate recombinase accessibility via localized, regional, or long-range changes in chromatin. PMID:20829065

Osipovich, Oleg; Oltz, Eugene M.

2010-01-01

329

Variable regions of Ig heavy chain genes encoding antithyrotropin receptor antibodies of patients with Graves' disease  

SciTech Connect

The authors have established EBV-transformed human B cell clones producing monoclonal antithyrotropin receptor antibodies from two patients with Graves' disease. They then isolated and characterized Ig H chain genes of 5 B cell clones with thyrotropin-binding inhibitor Ig (TBII) activity and 4 B cell clones with thyroid-stimulating antibody (TSAb) activity. They found that V[sub H] gene families used in the 5 TBII clones were diverse, including V[sub H-II, -III, -IV,] and [sub -V]. Most of V[sub H] segments used in TBII and TSAb are commonly used in other autoantibodies and fetal liver repertoire. The frequency of somatic mutations in TBII was higher than that in TSAb. In as much as the same germline V[sub H] segment (V3-23) was used for both TBII and TSAb, the frequency and position of somatic mutations may be important for generation of TBII and TSAb. 56 refs., 2 figs., 2 tabs.

Shin, Euy Kyun; Akamizu, Takashi; Matsuda, Fumihiko; Sugawa, Hideo; Fujikura, Junji; Mori, Toru; Honjo, Tasuku (Kyoto Univ. (Japan))

1994-02-01

330

Identification of a novel gene family that includes the interferon-inducible human genes 6–16 and ISG12  

Microsoft Academic Search

BACKGROUND: The human 6–16 and ISG12 genes are transcriptionally upregulated in a variety of cell types in response to type I interferon (IFN). The predicted products of these genes are small (12.9 and 11.5 kDa respectively), hydrophobic proteins that share 36% overall amino acid identity. Gene disruption and over-expression studies have so far failed to reveal any biochemical or cellular

Nadeene Parker; Andrew CG Porter

2004-01-01

331

Negative feedback regulation of reactive oxygen species on AT1 receptor gene expression  

PubMed Central

Free radicals as well as the AT1 receptor are involved in the pathogenesis of cardiovascular disease. Both the intracellular mechanisms of AT1 receptor regulation and the effect of free radicals on AT1 receptor expression are currently unknown. This study investigates the role of free radicals in the modulation of AT1 receptor expression and in the angiotensin II-induced AT1 receptor regulation. AT1 receptor mRNA was assessed by Northern blotting and AT1 receptor density by radioligand binding assays, respectively, in vascular smooth muscle cells (VSMC). Free radical release was measured by confocal laser scanning microscopy. AT1 receptor mRNA transcription rate was determined by nuclear run-on assays and AT1 receptor mRNA half-life was measured under transcriptional blockade. Angiotensin II caused a time-dependent decrease of AT1 receptor mRNA expression in rat VSMC in culture (30±6% at 4?h with 100?nM angiotensin II). This was followed by a consistent decrease in AT1 receptor density. Angiotensin II caused release of reactive oxygen species in VSMC which was abolished by preincubation with 100??M diphenylene iodonium (DPI). DPI inhibited partially the down-regulating effect of angiotensin II on the AT1 receptor. Incubation of VSMC with either hydrogen peroxide or xanthine/xanthine oxidase caused a dose-dependent decrease in AT1 receptor mRNA expression which was not mediated by a decreased rate of transcription but rather through destabilization of AT1 receptor mRNA. Experiments which included preincubation of VSMC with various intracellular inhibitors suggested that free radicals caused AT1 receptor downregulation through activation of p38-MAP kinase and intracellular release of calcium. However, angiotensin II-induced AT1 receptor expression was not inhibited by blockade of p38-MAP kinase activation or intracellular calcium release. Free radicals may at least in part mediate angiotensin II-induced AT1 receptor regulation through direct post-transcriptional effects on AT1 receptor mRNA expression which involves intracellular release of calcium and activation of p38-MAP kinase. These findings may help to clarify the intracellular mechanisms involved in AT1 receptor regulation and reveal a novel biological feature for reactive oxygen species. PMID:11030730

Nickenig, Georg; Strehlow, Kerstin; Bäumer, Anselm T; Baudler, Stefanie; Waßmann, Sven; Sauer, Heinrich; Böhm, Michael

2000-01-01

332

Identification of N-terminal receptor activity-modifying protein residues important for calcitonin gene-related peptide, adrenomedullin, and amylin receptor function.  

PubMed

Calcitonin-family receptors comprise calcitonin receptor-like receptor (CL) or calcitonin receptor and receptor activity-modifying protein (RAMP) pairings. Calcitonin gene-related peptide (CGRP) receptors are CL/RAMP1, whereas adrenomedullin (AM) receptors are CL/RAMP2 (AM1 receptor) or CL/RAMP3 (AM2 receptor). Amylin (Amy) receptors are RAMP hetero-oligomers with the calcitonin receptor (AMY1, AMY2, and AMY3, respectively). How RAMPs change G protein-coupled receptor pharmacology is not fully understood. We exploited sequence differences between RAMP1 and RAMP3 to identify individual residues capable of altering receptor pharmacology. Alignment of human RAMPs revealed eight residues that are conserved in RAMP2 and RAMP3 but are different in RAMP1. We hypothesized that residues in RAMP2 and RAMP3, but not RAMP1, are responsible for making CL/RAMP2 and CL/RAMP3 AM receptors. Using site-directed mutagenesis, we introduced individual RAMP3 residues into RAMP1 and vice versa in these eight positions. Mutant or wild-type RAMPs were transfected into Cos7 cells with CL or the insert-negative form of the calcitonin receptor [CT(a)]. Agonist-stimulated cAMP production and cell-surface expression of constructs were measured. Position 74 in RAMP1 and RAMP3 was critical for determining AM potency and affinity, and Phe93 in RAMP1 was an important contributor to alphaCGRP potency at CGRP receptors. Mutant RAMP/CT(a) receptor complexes displayed different phenotypes. It is noteworthy that RAMP1 S103N and W74E mutations led to enhanced rAmy potency, probably related to increased cell-surface expression of these complexes. This differs from the effect on CL-based receptors where expression was unchanged. Targeted substitution has emphasized the importance of position 74 in RAMP1/RAMP3 as a key determinant of AM pharmacology. PMID:18593822

Qi, Tao; Christopoulos, George; Bailey, Richard J; Christopoulos, Arthur; Sexton, Patrick M; Hay, Debbie L

2008-10-01

333

Epigenetic Control of Estrogen Receptor Expression and Tumor Suppressor Genes Is Modulated by Bioactive Food Compounds  

Microsoft Academic Search

Background: The tumor suppressor genes p15INK4b and p16INK4a as well as the estrogen receptor-? (ESR1) gene are abnormally methylated and expressed in colon cancer. The cancer-preventative abilities of several bioactive food components have been linked to their estrogenic and epigenetic activities. Methods: The effect of folic acid, zebularine, resveratrol, genistein and epigallocatechin-3-gallate (EGCG) on tumor cell growth, promoter methylation of

Carolin Berner; Eva Aumüller; Anne Gnauck; Manuela Nestelberger; A. Just; Alexander G. Haslberger

2010-01-01

334

Downstream Gene Activation of the Receptor ALX by the Agonist Annexin A1  

Microsoft Academic Search

BackgroundOur understanding of pro-resolution factors in determining the outcome of inflammation has recently gained ground, yet not many studies have investigated whether specific genes or patterns of genes, are modified by these mediators. Here, we have focussed on the glucocorticoid modulated pro-resolution factor annexin A1 (AnxA1), studying if its interaction with the ALX receptor would affect downstream genomic targets.Methodology\\/Principal FindingsUsing

Derek Renshaw; Trinidad Montero-Melendez; Jesmond Dalli; Ahmad Kamal; Vincenzo Brancaleone; Fulvio DAcquisto; Giuseppe Cirino; Mauro Perretti

2010-01-01

335

Epigenetic changes in the estrogen receptor ? gene promoter: implications in sociosexual behaviors  

PubMed Central

Estrogen action through estrogen receptor ? (ER?) is involved in the control of sexual and social behaviors in adult mammals. Alteration of ER? gene activity mediated by epigenetic mechanisms, such as histone modifications and DNA methylation, in particular brain areas appears to be crucial for determining the extents of these behaviors between the sexes and among individuals within the same sex. This review provides a summary of the epigenetic changes in the ER? gene promoter that correlate with sociosexual behaviors. PMID:25389384

Matsuda, Ken Ichi

2014-01-01

336

Association of polymorphisms in the estrogen receptor ? gene with body fat distribution  

Microsoft Academic Search

OBJECTIVE: To examine whether polymorphisms of the estrogen receptor (ER) ? gene are associated with body fat distribution.DESIGN: Cross-sectional, epidemiological study of two single-nucleotide polymorphisms, a T ? C (PvuII) and an A ? G (XbaI), in the first intron of the ER? gene.SUBJECTS: A total of 2238 community-dwelling middle-aged and elderly Japanese population (age: 40–79 y).MEASUREMENTS: The ER? genotypes

T Okura; M Koda; F Ando; N Niino; S Ohta; H Shimokata

2003-01-01

337

5HT 2A receptor gene polymorphisms in anorexia nervosa and bulimia nervosa  

Microsoft Academic Search

To examine the distribution of different polymorphisms in genes of the 5-HT system in patients with anorexia nervosa (AN) and bulimia nervosa (BN), we analyzed the distribution of a polymorphism (?1438G\\/A) and the presence of known mutations in 5-HT2A and 5-HT2C receptor genes in 168 Italian female patients affected by AN and BN. Patients with AN restricting type (ANr) only,

Benedetta Nacmias; Valdo Ricca; Andrea Tedde; Barbara Mezzani; Carlo Maria Rotella; Sandro Sorbi

1999-01-01

338

Estrogen Receptor 1 Gene (ESR1) is Associated with Restrictive Anorexia Nervosa  

Microsoft Academic Search

Anorexia nervosa (AN) is a highly heritable young-onset psychiatric illness the etiology of which remains unknown. Estrogen alpha and beta receptors, encoded by ESR1 and ESR2 genes, are involved in food intake regulation and eating behavior, and may have a potential role in AN. We performed a family-based association study of 17 single-nucleotide polymorphisms (SNPs) encompassing ESR1 and ESR2 genes

Audrey Versini; Nicolas Ramoz; Yann Le Strat; Susann Scherag; Stefan Ehrlich; Claudette Boni; Anke Hinney; Johannes Hebebrand; Lucia Romo; Julien-Daniel Guelfi; Philip Gorwood

2010-01-01

339

Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression  

Microsoft Academic Search

We have investigated the effects of ligation of the fibronectin receptor (FnR) on gene expression in rabbit synovial fibroblasts. Monoclonal antibodies to the FnR that block initial adhesion of fibroblasts to fibronectin induced the expression of genes encoding the secreted extracellular matrix-degrading metallo- proteinases collagenase and stromelysin. That induc- tion was a direct consequence of interaction with the FnR was

Zena Werb; Patrice M. Tremble; Ole Behrendtsen; Eileen Crowley; Caroline H. Damskytll

1989-01-01

340

A novel steroid thyroid hormone receptor-related gene inappropriately expressed in human hepatocellular carcinoma  

Microsoft Academic Search

We have previously isolated from a human hepatocellular carcinoma a hepatitis B virus integration in a 147-base-pair cellular DNA fragment, similar to steroid- and c-erb- A\\/thyroid-hormone receptor genes1. We have now cloned the corresponding complementary DNA from a human-liver cDNA library. Nucleotide sequence analysis revealed that the overall structure of the cellular gene, which we have named hap, is similar

Hugues de Thé; Agnès Marchio; Pierre Tiollais; Anne Dejean

1987-01-01

341

New Potential Ligand-Receptor Signaling Loops in Ovarian Cancer Identified in Multiple Gene Expression Studies  

Microsoft Academic Search

Based on the hypothesis that gene products involved in the same biological process would be coupled at transcriptional level, a previous study analyzed the correlation of the gene expression patterns of ligand-receptor (L-R) pairs to discover potential autocrine\\/paracrine signaling loops in different cancers (Graeber and Eisenberg. Nat Genet 2001; 29:295). By refining the starting database, a list of 511 L-R

Giancarlo Castellano; James F. Reid; Paola Alberti; Maria Luisa Carcangiu; Antonella Tomassetti; Silvana Canevari

342

Pseudohypoaldosteronism Type 1 due to a Novel Mutation in the Mineralocorticoid Receptor Gene  

Microsoft Academic Search

Background\\/Aims: Autosomal dominant pseudohypoaldosteronism type 1 is caused by mutations in the mineralocorticoid receptor (NR3C2) gene, often leading to life-threatening hyponatremia and hyperkalemia in the newborn period. We report a novel mutation in the NR3C2 gene, and report, for the first time, the association of well-treated pseudohypoaldosteronism with failure to thrive. This report additionally highlights the importance of aldosterone-sensitive sodium

Lindsey A. Loomba-Albrecht; Mato Nagel; Andrew A. Bremer

2010-01-01

343

Gene cloning, homology comparison and analysis of the main functional structure domains of beta estrogen receptor in Jining Gray goat.  

PubMed

To clarify the molecular evolution and characteristic of beta estrogen receptor (ER?) gene in Jining Gray goat in China, the entire ER? gene from Jining Gray goat ovary was amplified, identified and sequenced, and the gene sequences were compared with those of other animals. Functional structural domains and variations in DNA binding domains (DBD) and ligand binding domains (LBD) between Jining Gray goat and Boer goat were analyzed. The results indicate that the ER? gene in Jining Gray goat includes a 1584bp sequence with a complete open-reading-frame (ORF), encoding a 527 amino acid (aa) receptor protein. Compared to other species, the nucleotide homology is 73.9-98.9% and the amino acid homology is 79.5-98.5%. The main antigenic structural domains lie from the 97th aa to the 286th aa and from the 403rd aa to the 527th aa. The hydrophilicity and the surface probability of the structural domains are distributed throughout a range of amino acids. There are two different amino acids in the DBD and three different amino acids in the LBD between Jining Gray and Boer goats, resulting in dramatically different spatial structures for ER? protein. These differences may explain the different biological activities of ER? between the two goat species. This study firstly acquired the whole ER? gene sequence of Jining Gray goat with a complete open reading frame, and analyzed its gene evolutionary relationship and predicted its mainly functional structural domains, which may very help for further understanding the genome evolution and gene diversity of goat ER?. PMID:24929544

Liu, Hai-gang; Li, Hong-mei; Wang, Shu-ying; Huang, Li-bo; Guo, Hui-jun

2014-08-01

344

Glycolytic genes are targets of the nuclear receptor Ad4BP/SF-1.  

PubMed

Genetic deficiencies in transcription factors can lead to the loss of certain types of cells and tissue. The steroidogenic tissue-specific nuclear receptor Ad4BP/SF-1 (NR5A1) is one such gene, because mice in which this gene is disrupted fail to develop the adrenal gland and gonads. However, the specific role of Ad4BP/SF-1 in these biological events remains unclear. Here we use chromatin immunoprecipitation sequencing to show that nearly all genes in the glycolytic pathway are regulated by Ad4BP/SF-1. Suppression of Ad4BP/SF-1 by small interfering RNA reduces production of the energy carriers ATP and nicotinamide adenine dinucleotide phosphate, as well as lowers expression of genes involved in glucose metabolism. Together, these observations may explain tissue dysgenesis as a result of Ad4BP/SF-1 gene disruption in vivo. Considering the function of estrogen-related receptor ?, the present study raises the possibility that certain types of nuclear receptors regulate sets of genes involved in metabolic pathways to generate energy carriers. PMID:24727981

Baba, Takashi; Otake, Hiroyuki; Sato, Tetsuya; Miyabayashi, Kanako; Shishido, Yurina; Wang, Chia-Yih; Shima, Yuichi; Kimura, Hiroshi; Yagi, Mikako; Ishihara, Yasuhiro; Hino, Shinjiro; Ogawa, Hidesato; Nakao, Mitsuyoshi; Yamazaki, Takeshi; Kang, Dongchon; Ohkawa, Yasuyuki; Suyama, Mikita; Chung, Bon-Chu; Morohashi, Ken-Ichirou

2014-01-01

345

Cognitive deficits and changes in gene expression of NMDA receptors after prenatal methylmercury exposure.  

PubMed

Previous studies showed learning and memory deficit in adult rats that were prenatally exposed to methylmercury chloride (MMC) in an advanced stage of pregnancy (15 days). Under these conditions, the cognitive deficits found at 60 days of age paralleled particularly changes in the N-methyl-D-aspartate (NMDA) receptor characteristics. In the present study, we report the behavioral effects of a single oral dose of MMC (8 mg/kg) administered earlier at gestational day 8. The use of different learning and memory tests (passive avoidance, object recognition, water maze) showed a general cognitive impairment in the in utero-exposed rats tested at 60 days of age compared with matched controls. Considering the importance of the glutamatergic receptor system and its endogenous ligands in learning and memory process regulation, we surmised that MMC could affect the gene expression of NMDA receptor subtypes. The use of a sensitive RNase protection assay allowed the evaluation of gene expression of two families of NMDA receptors (NR-1 and NR-2 subtypes). The result obtained in 60-day-old rats prenatally exposed to MMC, showed increased mRNA levels of the NR-2B subunit in the hippocampus but not in the frontal cortex. The data suggest that the behavioral abnormalities of MMC-exposed rats might be ascribed to a neurotoxic effect of the metal that alters the gene expression of a specific NMDA receptor subunit in the hippocampus. PMID:12426146

Baraldi, Mario; Zanoli, Paola; Tascedda, Fabio; Blom, Joan M C; Brunello, Nicoletta

2002-10-01

346

The Nuclear Orphan Receptor CAR-Retinoid X Receptor Heterodimer Activates the Phenobarbital-Responsive Enhancer Module of the CYP2B Gene  

Microsoft Academic Search

PBREM, the phenobarbital-responsive enhancer module of the cytochrome P-450 Cyp2b10 gene, contains two potential nuclear receptor binding sites, NR1 and NR2. Consistent with the finding that anti-retinoid X receptor (RXR) could supershift the NR1-nuclear protein complex, DNA affinity chromatography with NR1 oligonucleotides enriched the nuclear orphan receptor RXR from the hepatic nuclear extracts of phenobar- bital-treated mice. In addition to

PAAVO HONKAKOSKI; IGOR ZELKO; TATSUYA SUEYOSHI; MASAHIKO NEGISHI

1998-01-01

347

The human PRR2 gene, related to the human poliovirus receptor gene ( PVR), is the true homolog of the murine MPH gene  

Microsoft Academic Search

Until now it was assumed that the murine poliovirus (PV) receptor homolog gene (MPH) had been identified. Alternative splicing of MPH transcripts generates two glycoproteins named MPH? and MPH? which share an identical N-terminal region composed of three immunoglobulin (Ig)-like domains and different C-terminal regions. Using a degenerate PCR strategy, we describe the identification of a second human PVR-related gene

Frédéric Eberlé; Patrice Dubreuil; Marie-Geneviève Mattei; Elisabeth Devilard; Marc Lopez

1995-01-01

348

Identification of a novel gene family that includes the interferon-inducible human genes 6–16and ISG12  

E-print Network

Abstract Background The human 6–16 and ISG12 genes are transcriptionally upregulated in a variety of cell types in response to type I interferon (IFN). The predicted products of these genes are small (12.9 and 11.5 kDa respectively), hydrophobic...

Parker, Nadeene; Porter, Andrew C G

2004-01-19

349

Adenovirus-Mediated Transfer of Low Density Lipoprotein Receptor Gene Acutely Accelerates Cholesterol Clearance in Normal Mice  

Microsoft Academic Search

We have explored the use of adenovirus-mediated gene transfer to transiently elicit production of low density lipoprotein (LDL) receptors in mice. A recombinant adenovirus carrying the human LDL receptor cDNA restored LDL receptor function in receptor-deficient cultured cells. Intravenous injection of recombinant virus acutely lowered plasma cholesterol levels and increased the rate of 125I-labeled LDL clearance from the circulation in

Joachim Herz; Robert D. Gerard

1993-01-01

350

Global analysis of estrogen receptor beta binding to breast cancer cell genome reveals an extensive interplay with estrogen receptor alpha for target gene regulation  

Microsoft Academic Search

BACKGROUND: Estrogen receptors alpha (ER?) and beta (ER?) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype of breast cancer (BC). The two receptors can be found co-expressed and play specific, often opposite, roles, with ER? being able to modulate the effects of ER? on gene transcription and cell proliferation. ER? is frequently lost in BC,

Oli MV Grober; Margherita Mutarelli; Giorgio Giurato; Maria Ravo; Luigi Cicatiello; Maria Rosaria De Filippo; Lorenzo Ferraro; Giovanni Nassa; Maria Francesca Papa; Ornella Paris; Roberta Tarallo; Shujun Luo; Gary P Schroth; Vladimir Benes; Alessandro Weisz

2011-01-01

351

Pseudogenization of a Sweet-Receptor Gene Accounts for Cats' Indifference toward Sugar  

PubMed Central

Although domestic cats (Felis silvestris catus) possess an otherwise functional sense of taste, they, unlike most mammals, do not prefer and may be unable to detect the sweetness of sugars. One possible explanation for this behavior is that cats lack the sensory system to taste sugars and therefore are indifferent to them. Drawing on work in mice, demonstrating that alleles of sweet-receptor genes predict low sugar intake, we examined the possibility that genes involved in the initial transduction of sweet perception might account for the indifference to sweet-tasting foods by cats. We characterized the sweet-receptor genes of domestic cats as well as those of other members of the Felidae family of obligate carnivores, tiger and cheetah. Because the mammalian sweet-taste receptor is formed by the dimerization of two proteins (T1R2 and T1R3; gene symbols Tas1r2 and Tas1r3), we identified and sequenced both genes in the cat by screening a feline genomic BAC library and by performing PCR with degenerate primers on cat genomic DNA. Gene expression was assessed by RT-PCR of taste tissue, in situ hybridization, and immunohistochemistry. The cat Tas1r3 gene shows high sequence similarity with functional Tas1r3 genes of other species. Message from Tas1r3 was detected by RT-PCR of taste tissue. In situ hybridization and immunohistochemical studies demonstrate that Tas1r3 is expressed, as expected, in taste buds. However, the cat Tas1r2 gene shows a 247-base pair microdeletion in exon 3 and stop codons in exons 4 and 6. There was no evidence of detectable mRNA from cat Tas1r2 by RT-PCR or in situ hybridization, and no evidence of protein expression by immunohistochemistry. Tas1r2 in tiger and cheetah and in six healthy adult domestic cats all show the similar deletion and stop codons. We conclude that cat Tas1r3 is an apparently functional and expressed receptor but that cat Tas1r2 is an unexpressed pseudogene. A functional sweet-taste receptor heteromer cannot form, and thus the cat lacks the receptor likely necessary for detection of sweet stimuli. This molecular change was very likely an important event in the evolution of the cat's carnivorous behavior. PMID:16103917

Li, Xia; Li, Weihua; Wang, Hong; Cao, Jie; Maehashi, Kenji; Huang, Liquan; Bachmanov, Alexander A; Reed, Danielle R; Legrand-Defretin, Véronique; Beauchamp, Gary K; Brand, Joseph G

2005-01-01

352

The human insulin receptor substrate-1 gene (IRS1) is localized on 2q36  

SciTech Connect

The chromosomal localization of some of the genes participating in the insulin signaling pathway is known. The insulin and insulin receptor genes have been mapped to chromosomes 11 and 19, respectively. To identify the chromosomal localization of the human IRS1 gene, the fluorescence in situ hybridization technique was employed with Genomic Clone B-10. A total of 50 metaphase cells exhibiting either single or double spots of hybridization signals were examined. Among them, 32 showed the specific signals on 2q36. Therefore, the authors assigned the human IRS1 gene to 2q36. The genes for homeobox sequence (HOX4), fibronectin 1, alkaline phosphatase (intestinal), transition protein 1, villin 1, collagen (type IV), Waardenburg syndrome (type 1), alanine-glyoxylate aminotransferase, and glucagon have been localized in the vicinity of the IRS1 gene.

Nishiyama, Masaki; Matsufuji, Senya; Hayashi, Shin-ichi; Furusaka, Akihiro; Tanaka, Teruji (Jikei Univ. School of Medicine, Tokyo (Japan)); Inazawa, J.; Nakamura, Yusuke (Cancer Institute, Tokyo (Japan)); Ariyama, Takeshi (Kyoto Prefactural Univ. of Medicine (Japan)); Wands, J.R. (Harvard Medical School, Boston, MA (United States))

1994-03-01

353

The leukemia inhibitory factor receptor (LIFR) gene is located within a cluster of cytokine receptor loci on mouse chromosome 15 and human chromosome 5p12-p13  

SciTech Connect

The leukemia inhibitory factor receptor (LIFR) gene was localized to human chromosome 5p12-p13 by somatic cell hybrid analysis. Interspecific backcross analysis revealed that the murine locus was on chromosome 15 in a region of homology with human chromosome 5p. In both human and mouse genomes, the LIFR locus was linked to the genes encoding the receptors for interleukin-7, prolactin, and growth hormone. 13 refs., 1 fig.

Gearing, D.P. (Immunex Research and Development Corp., Seattle, WA (United States)); Druck, T.; Huebner, K. (Jefferson Medical College, Philadelphia, PA (United States)); Overhauser, J. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Gilbert, D.J.; Copeland, N.G.; Jenkins, N.A. (NCI-Frederick Cancer Research and Development Center, MD (United States))

1993-10-01

354

Avian olfactory receptor gene repertoires: evidence for a well-developed sense of smell in birds?  

Microsoft Academic Search

Among vertebrates, the sense of smell is mediated by olfactory receptors (ORs) expressed in sensory neurons within the olfactory epithelium. Comparative genomic studies suggest that the olfactory acuity of mammalian species correlates positively with both the total number and the proportion of functional OR genes encoded in their genomes. In contrast to mammals, avian olfaction is poorly understood, with birds

Silke S. Steiger; Andrew E. Fidler; Mihai Valcu; Bart Kempenaers

2008-01-01

355

Thyroid Hormone Receptor  1 Directly Controls Transcription of the  -Catenin Gene in Intestinal Epithelial Cells  

Microsoft Academic Search

Thyroid hormones, T3 and T4, are known regulators of intestine development. The best characterized example is the remodeling of the gastrointestinal tract during amphibian metamorphosis. Thyroid hormones act via nuclear receptors, the TRs, which are T3-dependent transcription factors. We previously showed that intestinal epithelial cell proliferation is controlled by thyroid hormones and the TR gene. To analyze the mechanisms responsible,

Michelina Plateroti; Elsa Kress; Jun Ichirou Mori; Jacques Samarut

2006-01-01

356

Targeted Disruption of the Estrogen Receptor-Gene in Female Mice: Characterization of Ovarian Responses  

E-print Network

Targeted Disruption of the Estrogen Receptor- Gene in Female Mice: Characterization of Ovarian) results in a highly novel ovarian phenotype in the adult. The ERKO mouse model was used to char- acterize follicles, which in many cases formed large, hemorrhagic cysts. Corpora lutea were absent, which also

Mayo, Kelly E.

357

Estrogen Receptor Isoform Gene Expression in Ovarian Stromal and Epithelial Tumors  

Microsoft Academic Search

The factors involved in the pathogenesis of ovarian cancers remain unclear, and the response of these tumors to hormonal therapy is limited. The identification of a second estrogen receptor gene (ERb), expressed predominantly in ovarian granulosa cells, led us to explore its possible role in ovarian cancer, particularly in granulosa cell tu- mors (GCT). Several isoforms of ERb have been

SIMON CHU; PAM MAMERS; HENRY G. BURGER; PETER J. FULLER

2010-01-01

358

CHARACTERIZATION AND EXPRESSION OF THE CHICKEN PROGLUCAGON AND CORRESPONDING RECEPTOR GENES  

Technology Transfer Automated Retrieval System (TEKTRAN)

In mammals the proglucagon (PG) gene produces a single mRNA transcript that encodes glucagon and two glucagon-like peptide hormones (GLP-1 and GLP-2). These peptide hormones bind to specific receptors that are expressed in different tissues. The function of these hormones, in conjunction with thei...

359

Mutant Oocytic Low Density Lipoprotein Receptor Gene Family Member Causes Atherosclerosis and Female Sterility  

Microsoft Academic Search

The so-called very low density lipoprotein receptors (VLDLRs) are related to the LDLR gene family. So far, naturally occurring mutations have only been described for the prototype LDLR; in humans, they cause familial hypercholesterolemia. Here we describe a naturally occurring mutation in a VLDLR that causes a dramatic abnormal phenotype. Hens of the mutant restricted-ovulator chicken strain carry a single

Hideaki Bujo; Tokuo Yamamoto; Kozo Hayashi; Marcela Hermann; Johannes Nimpf; Wolfgang Johann Schneider

1995-01-01

360

Composition and evolution of the V2r vomeronasal receptor gene repertoire in mice and rats  

E-print Network

/sexual physiological and behavioral responses, and they are perceived primarily by the vomeronasal organ (VNO are probably sensed by the vomeronasal organ (VNO) in mammals [1]. VNO is encased in a bony capsuleComposition and evolution of the V2r vomeronasal receptor gene repertoire in mice and rats Hui

Zhang, Jianzhi

361

CAG repeat length in the androgen receptor gene of infertile Japanese males with oligozoospermia  

Microsoft Academic Search

We analysed the CAG repeat length in exon 1 of the androgen receptor gene in 59 idiopathic Japanese infertile males with oligozoospermia; 36 fertile males were also analysed as controls. The number of CAG repeats in infertile males ranged from 14 to 32 (mean 21.2 K 4.2), whereas the number of CAG repeats in fertile males ranged from 16 to

Shinji Komori; Hiroyuki Kasumi; Ri-ichiro Kanazawa; Kazuko Sakata; Yuko Nakata; Hiroshi Kato; Koji Koyama

1999-01-01

362

Clinical and Biological Features Associated With Epidermal Growth Factor Receptor Gene Mutations in Lung Cancers  

Microsoft Academic Search

Background: Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in lung cancers are associated with increased sensitivity of these can- cers to drugs that inhibit EGFR kinase activity. However, the role of such mutations in the pathogenesis of lung cancers is unclear. Methods: We sequenced exons 18 - 21 of the EGFR TK

Hisayuki Shigematsu; Li Lin; Takao Takahashi; Masaharu Nomura; Makoto Suzuki; Ignacio I. Wistuba; Kwun M. Fong; Huei Lee; Shinichi Toyooka; Nobuyoshi Shimizu; Takehiko Fujisawa; Ziding Feng; Jack A. Roth; Joachim Herz; John D. Minna; Adi F. Gazdar

363

Ovarian Cancer G Protein - Coupled Receptor 1, a New Metastasis Suppressor Gene in Prostate Cancer  

Microsoft Academic Search

Background Metastasis is a process by which tumors spread from primary organs to other sites in the body and is the major cause of death for cancer patients. The ovarian cancer G protein - coupled receptor 1 (OGR1) gene has been shown to be expressed at lower levels in metastatic compared with primary prostate cancer tissues. Methods We used an

Lisam Shanjukumar Singh; Michael Berk; Rhonda Oates; Zhenwen Zhao; Haiyan Tan; Ying Jiang; Aimin Zhou; Kashif Kirmani; Rosemary Steinmetz; Daniel Lindner; Yan Xu

2007-01-01

364

Sensory experience and sensory activity regulate chemosensory receptor gene expression in Caenorhabditis elegans  

PubMed Central

Changes in the environment cause both short-term and long-term changes in an animal's behavior. Here we show that specific sensory experiences cause changes in chemosensory receptor gene expression that may alter sensory perception in the nematode Caenorhabditis elegans. Three predicted chemosensory receptor genes expressed in the ASI chemosensory neurons, srd-1, str-2, and str-3, are repressed by exposure to the dauer pheromone, a signal of crowding. Repression occurs at pheromone concentrations below those that induce formation of the alternative dauer larva stage, suggesting that exposure to pheromones can alter the chemosensory behaviors of non-dauer animals. In addition, ASI expression of srd-1, but not str-2 and str-3, is induced by sensory activity of the ASI neurons. Expression of two receptor genes is regulated by developmental entry into the dauer larva stage. srd-1 expression in ASI neurons is repressed in dauer larvae. str-2 expression in dauer animals is induced in the ASI neurons, but repressed in the AWC neurons. The ASI and AWC neurons remodel in the dauer stage, and these results suggest that their sensory specificity changes as well. We suggest that experience-dependent changes in chemosensory receptor gene expression may modify olfactory behaviors. PMID:11572964

Peckol, Erin L.; Troemel, Emily R.; Bargmann, Cornelia I.

2001-01-01

365

Sensory experience and sensory activity regulate chemosensory receptor gene expression in Caenorhabditis elegans.  

PubMed

Changes in the environment cause both short-term and long-term changes in an animal's behavior. Here we show that specific sensory experiences cause changes in chemosensory receptor gene expression that may alter sensory perception in the nematode Caenorhabditis elegans. Three predicted chemosensory receptor genes expressed in the ASI chemosensory neurons, srd-1, str-2, and str-3, are repressed by exposure to the dauer pheromone, a signal of crowding. Repression occurs at pheromone concentrations below those that induce formation of the alternative dauer larva stage, suggesting that exposure to pheromones can alter the chemosensory behaviors of non-dauer animals. In addition, ASI expression of srd-1, but not str-2 and str-3, is induced by sensory activity of the ASI neurons. Expression of two receptor genes is regulated by developmental entry into the dauer larva stage. srd-1 expression in ASI neurons is repressed in dauer larvae. str-2 expression in dauer animals is induced in the ASI neurons, but repressed in the AWC neurons. The ASI and AWC neurons remodel in the dauer stage, and these results suggest that their sensory specificity changes as well. We suggest that experience-dependent changes in chemosensory receptor gene expression may modify olfactory behaviors. PMID:11572964

Peckol, E L; Troemel, E R; Bargmann, C I

2001-09-25

366

Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates  

E-print Network

Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates to a caregiver is crucial for infant survival and partly mediated by the endoge- nous opioids. Functional mu-opioid interacting with its mother are thought to be mediated in part by release of the endogenous opioids (4, 5

Maestripieri, Dario

367

Regulation of T cell receptor ? gene assembly by a complex hierarchy of germline J? promoters  

Microsoft Academic Search

Assembly of the gene encoding T cell receptor ? (Tcra) is characterized by an orderly progression of primary and secondary V?-to-J? recombination events across the J? array, but the targeting mechanisms responsible for this progression are mostly unknown. Studies have shown that the T early-? promoter is important in targeting primary Tcra rearrangements. We found that T early-? and a

Abbas Hawwari; Cheryl Bock; Michael S Krangel

2005-01-01

368

Androgen receptor gene GGN repeat length and reproductive characteristics in young Swedish men  

Microsoft Academic Search

Background: The human androgen receptor (AR) gene contains two polymorphisms of CAG and GGN repeats respectively. The GGN repeat function is still largely unknown and to date there are no in vivo data on this segment with respect to the general population. Methods: We investigated the impact of CAG and GGN repeats on male reproductive function, one by one and

K B Lundin; Y L Giwercman; L Rylander; L Hagmar; A Giwercman

2006-01-01

369

Ah receptor represses acute-phase response gene expression without binding to its cognate response  

E-print Network

a perceived stress. However, persistent pathophysiological conditions such as cancer or autoimmune diseasesAh receptor represses acute-phase response gene expression without binding to its cognate response. Dietary exposure to an AHR ligand represses cytokine-induced acute-phase response in the liver. Use

Perdew, Gary

370

Association of Polymorphisms for Prolactin and Prolactin Receptor Genes with Broody Traits in Chickens  

Microsoft Academic Search

Prolactin (PRL) is generally accepted as crucial to the onset and maintenance of broodiness in avian species. The prolactin receptor (PRLR) plays an important role in the PRL signal transduction cascade. Two candidate genes, PRL and PRLR, were screened for polymorphisms in the chicken, and their genetic effects on broodiness were evaluated. Pedigreed hens (n = 155) of the Blue-shell

R.-S. Jiang; G.-Y. Xu; X.-Q. Zhang; N. Yang

371

Three Retinoid X Receptor Gene Polymorphisms in Plaque Psoriasis and Psoriasis Guttata  

Microsoft Academic Search

Aim: Polymorphisms in retinoid X receptors (RXRs) are very interesting from the point of view of a possible association of their variability with psoriasis. Methods: A total of 293 patients with plaque psoriasis, 82 patients with psoriasis guttata and 202 control subjects were enrolled in this study focused on 3 polymorphisms in RXRA and RXRB gene associations. Results: A marginally

Monika Pávková Goldbergová

2007-01-01

372

Association of a nicotinic receptor gene polymorphism with spontaneous eyeblink rates  

PubMed Central

Spontaneous eyeblink rates greatly vary among individuals from several blinks to a few dozen blinks per minute. Because dopamine agonists immediately increase the blink rate, individual differences in blink rate are used as a behavioral index of central dopamine functioning. However, an association of the blink rate with polymorphisms in dopamine-related genes has yet not been found. In this study, we demonstrated that a genetic variation of the nicotinic acetylcholine receptor CHRNA4 (rs1044396) increased the blink rate while watching a video. A receiver operating characteristic analysis revealed that the blink rate predicts a genetic variation in the nicotinic receptor gene with a significant discrimination level (0.66, p < 0.004). The present study suggests that differences in sensitivity to acetylcholine because of the genetic variation of the nicotinic receptor are associated with individual differences in spontaneous eye blink rate. PMID:25729002

Nakano, Tamami; Kuriyama, Chiho; Himichi, Toshiyuki; Nomura, Michio

2015-01-01

373

Steroid receptor RNA activator (SRA1): unusual bifaceted gene products with suspected relevance to breast cancer  

PubMed Central

The steroid receptor RNA activator (SRA) is a unique modulator of steroid receptor transcriptional activity, as it is able to mediate its coregulatory effects as a RNA molecule. Recent findings, however, have painted a more complex picture of the SRA gene (SRA1) products. Indeed, even though SRA was initially thought to be noncoding, several RNA isoforms have now been found to encode an endogenous protein (SRAP), which is well conserved among Chordata. Although the function of SRAP remains largely unknown, it has been proposed that, much like its corresponding RNA, the protein itself might regulate estrogen and androgen receptor signaling pathways. As such, data suggest that both SRA and SRAP might participate in the mechanisms underlying breast, as well as prostate tumorigenesis. This review summarizes the published literature dealing with these two faces of the SRA gene products and underscores the relevance of this bifaceted system to breast cancer development. PMID:17710122

Leygue, Etienne

2007-01-01

374

Gene expression, localization, and characterization of endothelin A and B receptors in the human adrenal cortex.  

PubMed Central

Compelling evidence indicates that the endothelium-derived potent vasoconstrictor endothelin-1 (ET-1) stimulates aldosterone secretion by interacting with specific receptors. Although two different ET-1 receptors have been identified and cloned, the receptor subtype involved in mediating aldosterone secretion is still unknown. Accordingly, we wished to investigate whether the genes of ET-1 and of its receptors A and B are expressed in the normal human adrenal cortex. We designed specific primers for ET-1 and the ETA and ETB receptors genes and developed a reverse transcription polymerase chain reaction (RT-PCR) with chemiluminescent quantitation of the cDNA. In addition, we carried out 125I ET-1 displacement studies with cold ET-1, ET-3 and the specific ETA and ETB ligands BQ123 and sarafotoxin 6C. Localization of each receptor subtype was also investigated by autoradiography. Binding experiments were first individually analyzed by Scatchard and Hofstee plot and then coanalyzed by the nonlinear iterative curve fitting program Ligand. Histologically normal adrenal cortex tissue, obtained from kidney cancer patients (n = 7), and an aldosterone-producing adenoma (APA), which is histogenetically derived from the zona glomerulosa (ZG) cells, were studied. Results showed that the ET-1, ETA and ETB mRNA can be detected by RT-PCR in all adrenal cortices as well as in the APA. The best fitting of the 125I ET-1 displacement binding data was consistently provided by a two-site model both in the normal adrenal cortex (F = 22.1, P < 0.0001) and in the APA (F = 18.4, P < 0.0001). In the former the density (Bmax) of the ETA and ETB subtype was 2.6 +/- 0.5 pmol/mg protein (m +/- SEM) and 1.19 +/- 0.6, respectively. The dissociation constant (Kd) of ET-1, ET-3, S6C, and BQ-123 for each receptor subtype resulted to be within the range reported for human tissue for the ETA and ETB receptors. In the APA tissue the Bmax tended to be lower (1.33 and 0.8 pmol/mg protein, for the ETA and ETB, respectively) but the Kd were similar. Autoradiographic studies confirmed the presence of both receptor subtypes on the ZG as well as on APA cells. Thus, the genes of ET-1 and both its receptor subtypes ETA and ETB are actively transcribed in the human adrenal cortex. Furthermore, both receptor subtypes are translated into proteins in ZG and APA cells. Images PMID:8083364

Rossi, G; Albertin, G; Belloni, A; Zanin, L; Biasolo, M A; Prayer-Galetti, T; Bader, M; Nussdorfer, G G; Palù, G; Pessina, A C

1994-01-01

375

Age at first sexual intercourse, genes, and social context: Evidence from twins and the dopamine D4 receptor gene  

Microsoft Academic Search

We carried out two distinct types of genetic analysis with data from the National Longitudinal Study of Adolescent Health.\\u000a The first was a non-DNA twin analysis using monozygotic (identical) and same-sex dizygotic (fraternal) twins. The second analysis\\u000a investigates the association between age at first sexual intercourse and the 48-bp repeat polymorphism in the dopamine receptor\\u000a D4 gene (DRD4). The twin

Guang Guo; Yuying Tong

2006-01-01

376

Arabidopsis ETR1 and ERS1 Differentially Repress the Ethylene Response in Combination with Other Ethylene Receptor Genes1[W  

PubMed Central

The ethylene response is negatively regulated by a family of five ethylene receptor genes in Arabidopsis (Arabidopsis thaliana). The five members of the ethylene receptor family can physically interact and form complexes, which implies that cooperativity for signaling may exist among the receptors. The ethylene receptor gene mutations etr1-1(C65Y)(for ethylene response1-1), ers1-1(I62P) (for ethylene response sensor1-1), and ers1C65Y are dominant, and each confers ethylene insensitivity. In this study, the repression of the ethylene response by these dominant mutant receptor genes was examined in receptor-defective mutants to investigate the functional significance of receptor cooperativity in ethylene signaling. We showed that etr1-1(C65Y), but not ers1-1(I62P), substantially repressed various ethylene responses independent of other receptor genes. In contrast, wild-type receptor genes differentially supported the repression of ethylene responses by ers1-1(I62P); ETR1 and ETHYLENE INSENSITIVE4 (EIN4) supported ers1-1(I62P) functions to a greater extent than did ERS2, ETR2, and ERS1. The lack of both ETR1 and EIN4 almost abolished the repression of ethylene responses by ers1C65Y, which implied that ETR1 and EIN4 have synergistic effects on ers1C65Y functions. Our data indicated that a dominant ethylene-insensitive receptor differentially repressed ethylene responses when coupled with a wild-type ethylene receptor, which supported the hypothesis that the formation of a variety of receptor complexes may facilitate differential receptor signal output, by which ethylene responses can be repressed to different extents. We hypothesize that plants can respond to a broad ethylene concentration range and exhibit tissue-specific ethylene responsiveness with differential cooperation of the multiple ethylene receptors. PMID:22227969

Liu, Qian; Wen, Chi-Kuang

2012-01-01

377

Genomic imprinting of the human serotonin-receptor (HTR2) gene involved in development of retinoblastoma  

SciTech Connect

Epidemiological and genetic studies of retinoblastoma (RB) suggested that imprinted genes might be genetically linked to the RB gene. In this study, we found that the human serotonin-receptor, HTR2, gene, which had been mapped nearby the RB gene on chromosome 13, was expressed only in human fibroblasts with a maternal allele and not in cells without a maternal allele. The 5{prime} genomic region of the human HTR2 gene was cloned by PCR-mediated method. Only the 5{prime} region of the gene was methylated in cells with the maternal gene, and it was not methylated in cells without the maternal gene. A polymorphism of PvuII site of the gene was also found and useful for the segregation analysis in a family of an RB patient and for analysis of loss of heterozygosity on chromosome 13 in tumor and its parental origin. These results suggest that the human HTR2 gene might be affected by genomic imprinting and that exclusive expression of the maternal HTR2 gene may be associated with the delayed occurrence of RB, which had lost the maternal chromosome 13. 33 refs., 5 figs., 2 tabs.

Kato, Mitsuo V.; Nagayoshi, Mariko; Shimuzu, Takashi [Kyoto Univ. (Japan)] [and others

1996-11-01

378

Identification of potential regulatory motifs in odorant receptor genes by analysis of promoter sequences  

PubMed Central

Mouse odorant receptors (ORs) are encoded by >1000 genes dispersed throughout the genome. Each olfactory neuron expresses one single OR gene, while the rest of the genes remain silent. The mechanisms underlying OR gene expression are poorly understood. Here, we investigated if OR genes share common cis-regulatory sequences in their promoter regions. We carried out a comprehensive analysis in which the upstream regions of a large number of OR genes were compared. First, using RLM-RACE, we generated cDNAs containing the complete 5?-untranslated regions (5?-UTRs) for a total number of 198 mouse OR genes. Then, we aligned these cDNA sequences to the mouse genome so that the 5? structure and transcription start sites (TSSs) of the OR genes could be precisely determined. Sequences upstream of the TSSs were retrieved and browsed for common elements. We found DNA sequence motifs that are overrepresented in the promoter regions of the OR genes. Most motifs resemble O/E-like sites and are preferentially localized within 200 bp upstream of the TSSs. Finally, we show that these motifs specifically interact with proteins extracted from nuclei prepared from the olfactory epithelium, but not from brain or liver. Our results show that the OR genes share common promoter elements. The present strategy should provide information on the role played by cis-regulatory sequences in OR gene regulation. PMID:16902085

Michaloski, Jussara S.; Galante, Pedro A.F.

2006-01-01

379

Atypical expression of Drosophila gustatory receptor genes in sensory and central neurons.  

PubMed

Members of the Drosophila gustatory receptor (Gr) gene family are generally expressed in chemosensory neurons and are known to mediate the perception of sugars, bitter substrates, CO(2), and pheromones. The Gr gene family consists of 68 members, many of which are organized in gene clusters of up to six genes, yet only expression of about 15 Gr genes has been characterized in detail prior to this study. Here we describe the first comprehensive expression analysis of six highly conserved Gr genes, Gr28a and Gr28b.a to Gr28b.e. Four of these Gr genes are not only expressed in the characteristic pattern associated with previously analyzed Gr genes-chemosensory neurons of the gustatory and olfactory system-but several other types of sensory neurons and neurons in the brain. Specifically, we show that several of the Gr28 genes are expressed in abdominal multidendritic neurons, putative hygroreceptive neurons of the arista, neurons associated with the Johnston's organ, peripheral proprioceptive neurons in the legs, neurons in the larval and adult brain, and oenocytes. Thus, our findings suggest that some Gr genes are utilized in nongustatory roles in the nervous system and tissues involved in proprioception, hygroreception, and other sensory modalities. It is also possible that the Gr28 genes have chemosensory roles in the detection of internal ligands. PMID:18067151

Thorne, Natasha; Amrein, Hubert

2008-02-01

380

Inorganic phosphate regulates multiple genes during osteoblast differentiation, including Nrf2  

Microsoft Academic Search

The process of osteoblast differentiation and matrix mineralization requires a rise in alkaline phosphatase enzymatic activity resulting in the generation of free phosphate. The ability of inorganic phosphate to regulate gene transcription and cellular function represents a potentially novel extracellular signaling mechanism. Using microarray analysis we have identified a discrete set of genes that are either positively or negatively regulated

George R Beck; Elizabeth Moran; Nicole Knecht

2003-01-01

381

Resistance Gene Analogs in Rosaceae: Family-wide Classification Including Raspberry, Cherry, and Wild Apples  

Technology Transfer Automated Retrieval System (TEKTRAN)

Genetic studies have shown that NBS-LRR Resistance Gene Analogs (RGAs)tend to occur in clusters and often map to major resistance genes or QTLs. The identification and use of specific RGAs as molecular markers among plant material displaying different resistance phenotypes has the potential to direc...

382

Association study of the estrogen receptor gene ESR1 with post-partum depression – a pilot study  

PubMed Central

Perinatal mood disorders, such as postpartum depression (PPD) are costly for society, with potentially serious consequences for mother and child. While multiple genes appear to play a role in PPD susceptibility, the contributions of specific genetic variations remain unclear. Previously implicated as a candidate gene, the estrogen receptor alpha gene (ESR1) is a key player in mediating hormonal differences during pregnancy and the postpartum period. This study addresses genetic factors in perinatal mood disorders, testing 9 polymorphisms in ESR1. 257 postpartum women were screened for mood disorders, including 52 women with PPD and 32 without any symptoms of mood disorders. We detected a significant association for the upstream TA microsatellite repeat with the Edinburgh Postnatal Depression Scale (p=0.007). The same variant was also associated with the occurrence of PPD. Separately, 11 candidate functional polymorphisms in 7 additional genes were genotyped to investigate gene-gene interaction with the ESR1 TA repeat, identifying a potential interaction with the serotonin transporter. Our results support a role for ESR1 in the etiology of PPD, possibly through the modulation of serotonin signaling. Our findings for ESR1 could have broad implications for other disorders and therapies that involve estrogens. PMID:23917948

Pinsonneault, Julia K.; Sullivan, Danielle; Sadee, Wolfgang; Soares, Claudio N.; Hampson, Elizabeth; Steiner, Meir

2013-01-01

383

Systematic screening for mutations in the human serotonin 1F receptor gene in patients with bipolar affective disorder and schizophrenia  

SciTech Connect

Using single strand conformational analysis we screened the complete coding sequence of the serotonin 1F (5-HT{sub 1F}) receptor gene for the presence of DNA sequence variation in a sample of 137 unrelated individuals including 45 schizophrenic patients, 46 bipolar patients, as well as 46 healthy controls. We detected only three rare sequence variants which are characterized by single base pair substitutions, namely a silent T{r_arrow}A transversion in the third position of codon 261 (encoding isoleucine), a silent C{r_arrow}T transition in the third position of codon 176 (encoding histidine), and a C{r_arrow}T transition in position -78 upstream from the start codon. The lack of significant mutations in patients suffering from schizophrenia and bipolar affective disorder indicates that the 5-HT{sub 1F} receptor is not commonly involved in the etiology of these diseases. 12 refs., 1 fig., 2 tabs.

Shimron-Abarbanell, D.; Harms, H.; Erdmann, J.; Propping, P.; Noethen, M.M. [Univ. of Bonn (Germany)] [and others] [Univ. of Bonn (Germany); and others

1996-04-09

384

Calcitonin Gene-Related Peptide (CGRP) Receptors Are Important to Maintain Cerebrovascular Reactivity in Chronic Hypertension  

PubMed Central

Cerebral blood flow autoregulation (CA) shifts to higher blood pressures in chronic hypertensive patients, which increases their risk for brain damage. Although cerebral vascular smooth muscle cells express the potent vasodilatatory peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) and their receptors (calcitonin receptor-like receptor (Calclr), receptor-modifying proteins (RAMP) 1 and 2), their contribution to CA during chronic hypertension is poorly understood. Here we report that chronic (10 weeks) hypertensive (one-kidney-one-clip-method) mice overexpressing the Calclr in smooth muscle cells (CLR-tg), which increases the natural sensitivity of the brain vasculature to CGRP and AM show significantly better blood pressure drop-induced cerebrovascular reactivity than wt controls. Compared to sham mice, this was paralleled by increased cerebral CGRP-binding sites (receptor autoradiography), significantly in CLR-tg but not wt mice. AM-binding sites remained unchanged. Whereas hypertension did not alter RAMP-1 expression (droplet digital (dd) PCR) in either mouse line, RAMP-2 expression dropped significantly in both mouse lines by about 65%. Moreover, in wt only Calclr expression was reduced by about 70% parallel to an increase of smooth muscle actin (Acta2) expression. Thus, chronic hypertension induces a stoichiometric shift between CGRP and AM receptors in favor of the CGRP receptor. However, the parallel reduction of Calclr expression observed in wt mice but not CLR-tg mice appears to be a key mechanism in chronic hypertension impairing cerebrovascular reactivity. PMID:25860809

Wang, Zhenghui; Martorell, Belén Cantó; Wälchli, Thomas; Vogel, Olga; Fischer, Jan; Born, Walter; Vogel, Johannes

2015-01-01

385

Positive Evolutionary Selection On the RIG-I-Like Receptor Genes in Mammals  

PubMed Central

The mammalian RIG-I-like receptors, RIG-I, MDA5 and LGP2, are a family of DExD/H box RNA helicases responsible for the cytoplasmic detection of viral RNA. These receptors detect a variety of RNA viruses, or DNA viruses that express unusual RNA species, many of which are responsible for a great number of severe and lethal diseases. Host innate sentinel proteins involved in pathogen recognition must rapidly evolve in a dynamic arms race with pathogens, and thus are subjected to long-term positive selection pressures to avoid potential infections. Using six codon-based Maximum Likelihood methods, we were able to identify specific codons under positive selection in each of these three genes. The highest number of positively selected codons was detected in MDA5, but a great percentage of these codons were located outside of the currently defined protein domains for MDA5, which likely reflects the imposition of both functional and structural constraints. Additionally, our results support LGP2 as being the least prone to evolutionary change, since the lowest number of codons under selection was observed for this gene. On the other hand, the preponderance of positively selected codons for RIG-I were detected in known protein functional domains, suggesting that pressure has been imposed by the vast number of viruses that are recognized by this RNA helicase. Furthermore, the RIG-I repressor domain, the region responsible for recognizing and binding to its RNA substrates, exhibited the strongest evidence of selective pressures. Branch-site analyses were performed and several species branches on the three receptor gene trees showed evidence of episodic positive selection. In conclusion, by looking for evidence of positive evolutionary selection on mammalian RIG-I-like receptor genes, we propose that a multitude of viruses have crafted the receptors biological function in host defense, specifically for the RIG-I gene, contributing to the innate species-specific resistance/susceptibility to diverse viral pathogens. PMID:24312370

Lemos de Matos, Ana; McFadden, Grant; Esteves, Pedro J.

2013-01-01

386

Identification and Functional Analysis of Pheromone and Receptor Genes in the B3 Mating Locus of Pleurotus eryngii  

PubMed Central

Pleurotus eryngii has recently become a major cultivated mushroom; it uses tetrapolar heterothallism as a part of its reproductive process. Sexual development progresses only when the A and B mating types are compatible. Such mating incompatibility occasionally limits the efficiency of breeding programs in which crossing within loci-shared strains or backcrossing strategies are employed. Therefore, understanding the mating system in edible mushroom fungi will help provide a short cut in the development of new strains. We isolated and identified pheromone and receptor genes in the B3 locus of P. eryngii and performed a functional analysis of the genes in the mating process by transformation. A genomic DNA library was constructed to map the entire mating-type locus. The B3 locus was found to contain four pheromone precursor genes and four receptor genes. Remarkably, receptor PESTE3.3.1 has just 34 amino acid residues in its C-terminal cytoplasmic region; therefore, it seems likely to be a receptor-like gene. Real-time quantitative RT-PCR (real-time qRT-PCR) revealed that most pheromone and receptor genes showed significantly higher expression in monokaryotic cells than dikaryotic cells. The pheromone genes PEphb3.1 and PEphb3.3 and the receptor gene PESTE3.3.1 were transformed into P5 (A3B4). The transformants were mated with a tester strain (A4B4), and the progeny showed clamp connections and a normal fruiting body, which indicates the proposed role of these genes in mating and fruiting processes. This result also confirms that PESTE3.3.1 is a receptor gene. In this study, we identified pheromone and receptor genes in the B3 locus of P. eryngii and found that some of those genes appear to play a role in the mating and fruiting processes. These results might help elucidate the mechanism of fruiting differentiation and improve breeding efficiency. PMID:25133513

Kim, Kyung-Hee; Kang, Young Min; Im, Chak Han; Ali, Asjad; Kim, Sun Young; Je, Hee-Jeong; Kim, Min-Keun; Rho, Hyun Su; Lee, Hyun Sook; Kong, Won-Sik; Ryu, Jae-San

2014-01-01

387

Eliminating epigenetic barriers induces transient hormone-regulated gene expression in estrogen receptor negative breast cancer cells  

Microsoft Academic Search

In breast cancer, approximately one-third of tumors express neither the estrogen receptor (ER?) nor estrogen-regulated genes such as the progesterone receptor gene (PR). Our study provides new insights into the mechanism allowing hormone-activated expression of ER? target genes silenced in ER?-negative mammary tumor cells. In cell lines derived from ER?-negative MDA-MB231 cells, stable expression of different levels of ER? from

L Fleury; M Gerus; A C Lavigne; H Richard-Foy; K Bystricky

2008-01-01

388

Distinct, genome-wide, gene-specific selectivity patterns of four glucocorticoid receptor coregulators.  

PubMed

Glucocorticoids are a class of steroid hormones that bind to and activate the glucocorticoid receptor (GR), which then positively or negatively regulates transcription of many genes that govern multiple important physiological pathways such as inflammation and metabolism of glucose, fat and bone. The remodeling of chromatin and regulated assembly or disassembly of active transcription complexes by GR and other DNA-binding transcription factors is mediated and modulated by several hundred transcriptional coregulator proteins. Previous studies focusing on single coregulators demonstrated that each coregulator is required for regulation of only a subset of all the genes regulated by a steroid hormone. We hypothesized that the gene-specific patterns of coregulators may correspond to specific physiological pathways such that different coregulators modulate the pathway-specificity of hormone action, thereby providing a mechanism for fine tuning of the hormone response. We tested this by direct comparison of multiple coregulators, using siRNA to deplete the products of four steroid hormone receptor coregulator genes (CCAR1, CCAR2, CALCOCO1 and ZNF282). Global analysis of glucocorticoid-regulated gene expression after siRNA mediated depletion of coregulators confirmed that each coregulator acted in a selective and gene-specific manner and demonstrated both positive and negative effects on glucocorticoid-regulated expression of different genes. We identified several classes of hormone-regulated genes based on the effects of coregulator depletion. Each coregulator supported hormonal regulation of some genes and opposed hormonal regulation of other genes (coregulator-modulated genes), blocked hormonal regulation of a second class of genes (coregulator-blocked genes), and had no effect on hormonal regulation of a third gene class (coregulator-independent genes). In spite of previously demonstrated physical and functional interactions among these four coregulators, the majority of the several hundred modulated and blocked genes for each of the four coregulators tested were unique to that coregulator. Finally, pathway analysis on coregulator-modulated genes supported the hypothesis that individual coregulators may regulate only a subset of the many physiological pathways controlled by glucocorticoids. We conclude that gene-specific actions of coregulators correspond to specific physiological pathways, suggesting that coregulators provide a potential mechanism for physiological fine tuning in vivo and may thus represent attractive targets for therapeutic intervention. PMID:25422592

Wu, Dai-Ying; Ou, Chen-Yin; Chodankar, Rajas; Siegmund, Kimberly D; Stallcup, Michael R

2014-01-01

389

Distinct, genome-wide, gene-specific selectivity patterns of four glucocorticoid receptor coregulators  

PubMed Central

Glucocorticoids are a class of steroid hormones that bind to and activate the glucocorticoid receptor (GR), which then positively or negatively regulates transcription of many genes that govern multiple important physiological pathways such as inflammation and metabolism of glucose, fat and bone. The remodeling of chromatin and regulated assembly or disassembly of active transcription complexes by GR and other DNA-binding transcription factors is mediated and modulated by several hundred transcriptional coregulator proteins. Previous studies focusing on single coregulators demonstrated that each coregulator is required for regulation of only a subset of all the genes regulated by a steroid hormone. We hypothesized that the gene-specific patterns of coregulators may correspond to specific physiological pathways such that different coregulators modulate the pathway-specificity of hormone action, thereby providing a mechanism for fine tuning of the hormone response. We tested this by direct comparison of multiple coregulators, using siRNA to deplete the products of four steroid hormone receptor coregulator genes (CCAR1, CCAR2, CALCOCO1 and ZNF282). Global analysis of glucocorticoid-regulated gene expression after siRNA mediated depletion of coregulators confirmed that each coregulator acted in a selective and gene-specific manner and demonstrated both positive and negative effects on glucocorticoid-regulated expression of different genes. We identified several classes of hormone-regulated genes based on the effects of coregulator depletion. Each coregulator supported hormonal regulation of some genes and opposed hormonal regulation of other genes (coregulator-modulated genes), blocked hormonal regulation of a second class of genes (coregulator-blocked genes), and had no effect on hormonal regulation of a third gene class (coregulator-independent genes). In spite of previously demonstrated physical and functional interactions among these four coregulators, the majority of the several hundred modulated and blocked genes for each of the four coregulators tested were unique to that coregulator. Finally, pathway analysis on coregulator-modulated genes supported the hypothesis that individual coregulators may regulate only a subset of the many physiological pathways controlled by glucocorticoids. We conclude that gene-specific actions of coregulators correspond to specific physiological pathways, suggesting that coregulators provide a potential mechanism for physiological fine tuning in vivo and may thus represent attractive targets for therapeutic intervention. PMID:25422592

Wu, Dai-Ying; Ou, Chen-Yin; Chodankar, Rajas; Siegmund, Kimberly D.; Stallcup, Michael R.

2014-01-01

390

Sensory genes and mate choice: Evidence that duplications, mutations, and adaptive evolution alter variation in mating cue genes and their receptors  

E-print Network

Review Sensory genes and mate choice: Evidence that duplications, mutations, and adaptive evolution alter variation in mating cue genes and their receptors Lisa Horth Department of Biological Sciences genomics, and genetic engineering, precisely establish which genes are involved in mate choice and mating

Musselman, Lytton John

391

Characterization of SQUAMOSA-like genes in Gerbera hybrida, including one involved in reproductive transition  

PubMed Central

Background The flowering process in plants proceeds through the induction of an inflorescence meristem triggered by several pathways. Many of the genes associated with both the flowering process and floral architecture encode transcription factors of the MADS domain family. Gerbera, a member of the sunflower family, Asteraceae, bears compressed inflorescence heads (capitula) with three different flower types characterized by differences in both sexuality and floral symmetry. To understand how such a complex inflorescence structure is achieved at the molecular level, we have characterized the array of Gerbera MADS box genes. The high number of SQUAMOSA-like genes in Gerbera compared to other model species raised the question as to whether they may relate to Gerbera's complex inflorescence structure and whether or not a homeotic A function is present. Results In this paper we describe six Gerbera genes related to the SQUAMOSA/APETALA1/FRUITFULL genes of snapdragon and Arabidopsis. Based on phylogenetic analysis of the entire gene lineage, our data indicates that GSQUA1 and GSQUA3 are members of the SQUA/AP1 clade, while GSQUA2, GSQUA4, GSQUA5 and GSQUA6 are co-orthologs of the Arabidopsis FUL gene. GSQUA1/GSQUA3 and GSQUA4/GSQUA5/GSQUA6, respectively, represent several gene duplication events unknown in the model systems that may be specific to either Gerbera or Asteraceae. GSQUA genes showed specific expression profiles. GSQUA1, GSQUA2, and GSQUA5 were inflorescence abundant, while GSQUA3, GSQUA4, and GSQUA6 expression was also detected in vegetative organs. Overexpression of GSQUA2 in Gerbera led to accelerated flowering, dwarfism and vegetative abnormalities, all new and specific phenomena observed in transgenic Gerbera plants with modified MADS box gene expression. Conclusions Based on expression patterns, none of the Gerbera SQUA-like genes are likely to control flower organ identity in the sense of the floral A function. However, our data shows that the FUL-like gene GSQUA2 plays a vital role in meristem transition. The roles of other GSQUA-genes in Gerbera floral development are intriguing, but require still further study. PMID:20579337

2010-01-01

392

Use of an Activated Beta-Catenin to Identify Wnt Pathway Target Genes in Caenorhabditis elegans, Including a Subset of Collagen Genes Expressed in Late Larval Development  

PubMed Central

The Wnt signaling pathway plays a fundamental role during metazoan development, where it regulates diverse processes, including cell fate specification, cell migration, and stem cell renewal. Activation of the beta-catenin?dependent/canonical Wnt pathway up-regulates expression of Wnt target genes to mediate a cellular response. In the nematode Caenorhabditis elegans, a canonical Wnt signaling pathway regulates several processes during larval development; however, few target genes of this pathway have been identified. To address this deficit, we used a novel approach of conditionally activated Wnt signaling during a defined stage of larval life by overexpressing an activated beta-catenin protein, then used microarray analysis to identify genes showing altered expression compared with control animals. We identified 166 differentially expressed genes, of which 104 were up-regulated. A subset of the up-regulated genes was shown to have altered expression in mutants with decreased or increased Wnt signaling; we consider these genes to be bona fide C. elegans Wnt pathway targets. Among these was a group of six genes, including the cuticular collagen genes, bli-1col-38, col-49, and col-71. These genes show a peak of expression in the mid L4 stage during normal development, suggesting a role in adult cuticle formation. Consistent with this finding, reduction of function for several of the genes causes phenotypes suggestive of defects in cuticle function or integrity. Therefore, this work has identified a large number of putative Wnt pathway target genes during larval life, including a small subset of Wnt-regulated collagen genes that may function in synthesis of the adult cuticle. PMID:24569038

Jackson, Belinda M.; Abete-Luzi, Patricia; Krause, Michael W.; Eisenmann, David M.

2014-01-01

393

NMDA receptor gene variations as modifiers in Huntington disease: a replication study.  

PubMed

Several candidate modifier genes which, in addition to the pathogenic CAG repeat expansion, influence the age at onset (AO) in Huntington disease (HD) have already been described. The aim of this study was to replicate association of variations in the N-methyl D-aspartate receptor subtype genes GRIN2A and GRIN2B in the "REGISTRY" cohort from the European Huntington Disease Network (EHDN). The analyses did replicate the association reported between the GRIN2A rs2650427 variation and AO in the entire cohort. Yet, when subjects were stratified by AO subtypes, we found nominally significant evidence for an association of the GRIN2A rs1969060 variation and the GRIN2B rs1806201 variation. These findings further implicate the N-methyl D-aspartate receptor subtype genes as loci containing variation associated with AO in HD. PMID:21989477

Saft, Carsten; Epplen, Jörg T; Wieczorek, Stefan; Landwehrmeyer, G Bernhard; Roos, Raymund A C; de Yebenes, Justo Garcia; Dose, Matthias; Tabrizi, Sarah J; Craufurd, David; Arning, Larissa

2011-01-01

394

Structural and phylogenetic analysis of the MHC class I-like Fc receptor gene  

SciTech Connect

The intestinal epithelium of neonatal mice and rats expresses an Fc receptor that mediates selective uptake of IgG in mothers`milk. This receptor (FcRn), which helps newborn animals to acquire passive immunity, is an MHC class I-like heterodimer made up of a heavy chain and {beta}{sub 2}-microglobulin. In the present study, we determined the genomic structure of a mouse gene (FcRn) encoding the heavy of FcRn. The overall exon-intron organization of the Fcrn gene was similar to that of the Fcrn gene, thus providing structural evidence that Fcrn os a bona fide class I gene. The 5{prime}-flanking region of the Fcrn gene contained the binding motifs for two cytokine-inducible transcription factors, NF-IL6 and NF1. However, regulatory elements found in MHC class I genes (enhancer A, enhancer B, and the IFN response element) were absent. Phylogenetic tree analysis suggested that, like the MICA, AZGP1, and CD1 genes, the Fcrn gene diverged form MHC class I genes after the emergence of amphibians but before the split of placental and marsupial mammals. Consistent with this result, Southern blot analysis with a mouse Fcrn cDNA probe detected cross-hybridizing bands in various mammalian species and chickens. Sequence analysis of the Fcrn gene isolated from eight mouse strains showed that the membrane-distal domain of FcRn has at least three amino acid variants. The fact that Fcrn is a single copy gene indicates that it is expressed in both the neonatal intestine and the fetal yolk sac. 74 refs., 7 figs., 2 tabs.

Kandil, Eman; Ishibashi, Teruo; Kasahara, Masanori [Hokkaido University School of Medicine, Sapporo (Japan)] [and others

1995-06-01

395

Polymorphisms in the Calcium-Sensing Receptor Gene Are Associated with Clinical Outcome of Neuroblastoma  

PubMed Central

Background Neuroblastic tumors include the neuroblastomas, ganglioneuroblastomas, and ganglioneuromas. Clinical behavior of these developmental malignancies varies from regression to aggressive growth with metastatic dissemination. Several clinical, histological, genetic, and biological features are associated with this diversity of clinical presentations. The calcium-sensing receptor (CaSR) is a G-protein coupled receptor with a key role in calcium homeostasis. We have previously reported that it is expressed in benign, differentiated neuroblastic tumors, but silenced by genetic and epigenetic events in unfavorable neuroblastomas. We have now analyzed three functionally relevant polymorphisms clustered at the signal transduction region of the CaSR (rs1801725, rs1042636 and rs1801726) to assess if genetic variants producing a less active receptor are associated with more aggressive disease course. Methods Polymorphisms were analyzed in DNA samples from 65 patients using specific Taqman Genotyping Assays. Results Mildly inactivating variant rs1801725 was associated with clinical stage 4 (P?=?0.002) and the histological subgroup of undifferentiated neuroblastomas (P?=?0.046). Patients harboring this polymorphism had significantly lower overall (P?=?0.022) and event-free survival (P?=?0.01) rates than those who were homozygous for the most common allele among Caucasians. However, this single locus genotype was not independently associated with outcome in multivariate analyses. Conversely, the tri-locus haplotype TAC was independently associated with an increased risk of death in the entire cohort (Hazard Ratio?=?2.45; 95% Confidence Interval [1.14–5.29]; P?=?0.022) and also in patients diagnosed with neuroblastomas (Hazard Ratio?=?2.74; 95% Confidence Interval [1.20–6.25]; P?=?0.016). Conclusions The TAC haplotype includes the moderately inactivating variant rs1801725 and absence of the gain-of-function rs1042636 polymorphism. Thus, its association with metastatic disease and poor outcome would add to our previous data and further support that inactivation of the CaSR gene is a mechanism associated with neuroblastoma malignant behavior. PMID:23533647

Casalà, Carla; Galván, Patricia; Rodríguez, Eva; Lavarino, Cinzia; Mora, Jaume; de Torres, Carmen

2013-01-01

396

Antidepressant drugs inhibit glucocorticoid receptor-mediated gene transcription – a possible mechanism  

PubMed Central

Antidepressant drugs are known to inhibit some changes evoked by glucocorticoids, as well as a hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis, often observed in depression.The aim of present study was to investigate effects of various antidepressant drugs on the glucocorticoid-mediated gene transcription in fibroblast cells, stably transfected with an MMTV promoter (LMCAT cells).The present study have shown that antidepressants (imipramine, amitriptyline, desipramine, fluoxetine, tianeptine, mianserin and moclobemide), but not cocaine, inhibit the corticosterone-induced gene transcription in a concentration- and a time-dependent manner.Drugs which are known to augment clinical effects of medication in depressed patients (lithium chloride, amantadine, memantine), do not affect the inhibitory effects of imipramine on the glucocorticoid receptor (GR)-mediated gene transcription.Inhibitors of phospholipase C (PLC), protein kinase C (PKC), Ca2+/calmodulin-dependent protein kinase (CaMK) and antagonists of the L-type Ca2+ channel also inhibit the corticosterone-induced gene transcription.Inhibitors of protein kinase A (PKA) and protein kinase G (PKG) are without effect on the GR-induced gene transcription.Phorbol ester (an activator of PKC) attenuates the inhibitory effect of imipramine on the GR-induced gene transcription.Imipramine decreases binding of corticosterone-receptor complex to DNA.It is concluded that antidepressant drugs inhibit the corticosterone-induced gene transcription, and that the inhibitory effect of imipramine depends partly on the PLC/PKC pathway. PMID:10903980

Budziszewska, Bogus?awa; Jaworska-Feil, Lucylla; Kajta, Ma?gorzata; Laso?, W?adys?aw

2000-01-01