JournalToxicological Sciences : An Official Journal of the Society of Toxicology
PubMed ID
4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine (DMP 904) is a potent and selective antagonist of corticotropin releasing factor receptor-1 (CRF1 receptor) with an efficacious anxiolytic profile in preclinical animal models. In subchronic toxicity studies in Sprague-Dawley rats, DMP 904 produced thyroid follicular cell hypertrophy and hyperplasia, and a low incidence of follicular cell adenoma. The ... More
RAGE ligand upregulation of VEGF secretion in ARPE-19 cells.
AuthorsMa W; Lee SE; Guo J; Qu W; Hudson BI; Schmidt AM; Barile GR
JournalInvestigative Ophthalmology & Visual Science
PubMed ID
PURPOSE: The importance of VEGF in stimulating neovascular age-related macular degeneration (AMD) is well-recognized, but the initiating factors that induce local upregulation of VEGF remain unclear. The current study was conducted to test the hypothesis that activation of RAGE (receptor for advanced glycation end products [AGEs]) by its ligands, including ... More
SEROTONIN POLYMORPHISMS AND POSTTRAUMATIC STRESS DISORDER IN A TRAUMA EXPOSED AFRICAN AMERICAN POPULATION
Background: Genetic polymorphisms that influence serotonin (5-hydroxytryptamine, 5HT) neurotransmission are candidates for contributing to susceptibility to posttraumatic stress disorder (PTSD). The objective of our study was to determine if a variable length polymorphism for the promoter regions of the 5HT transporter (5HTTLPR), and/or a substitution polymorphism. in the promoter region ... More
Cognitive Flexibility is Associated with KIBRA Variant and Modulated by Recent Tobacco Use
The kidney and brain expressed protein gene (KIBRA) and the calsyntenin 2 gene (CLSTN2) are reportedly involved in synaptic plasticity. Single nucleotide polymorphisms (SNPs) rs17070145 (KIBRA) and rs6439886 (CLSTN2) have been found to affect memory performance measures. This study examined the association of KIBRA SNP rs17070145 and CLSTN2 SNPs rs6439886 ... More
Phenomic determinants of genomic variation in autism spectrum disorders
AuthorsQiao, Y; Riendeau, N; Koochek, M; Liu, X; Harvard, C; Hildebrand, MJ; Holden, JJA; Rajcan-Separovic, E; Lewis, MES
JournalJournal of Medical Genetics
PubMed ID
Background: Autism spectrum disorders (ASDs) are common, heritable neurobiologic conditions of unknown aetiology confounded by significant clinical and genetic heterogeneity. Methods: This study evaluated a broad categorisation of phenotypic traits (or phenome) for 100 subjects with Autism Diagnostic Interview-Revised/Autism Diagnostic Observation Schedule-Generic (ADI-R/ADOS-G) confirmed idiopathic ASD undergoing 1 Mb ... More
Is there a uniform basal endometrial gene expression profile during the implantation window in women who became pregnant in a subsequent ICSI cycle?
To understand which genes are really involved in the implantation process, we planned to study the gene basal expression profile during the window of implantation (WOI) of patients who became pregnant in a subsequent ICSI cycle. Women attending their first ICSI cycle at ANDROS Day Surgery for severe male factor ... More
AuthorsLuczynski, W; Kowalczuk, O; Stasiak-Barmuta, A; Ilendo, E; Krawczuk-Rybak, M; Chyczewski, L
JournalNEOPLASMA
PubMed ID
In all types of leukemia both in children and adults there is a need for novel therapies that could reduce the risk of relapse after standard treatment. Acute lymphoblastic leukemia (ALL) cells are ineffective antigen presenting cells, but as shown by many authors including results from our laboratory, stimulation with ... More
Intracellular biology and virulence determinants of Francisella tularensis revealed by transcriptional profiling inside macrophages
The highly infectious bacterium Francisella tularensis is a facultative intracellular pathogen, whose virulence requires proliferation inside host cells, including macrophages. Here we have performed a global transcriptional profiling of the highly virulent F. tularensis ssp. tularensis Schu S4 strain during its intracellular cycle within primary murine macrophages, to characterize its ... More
Preclinical Evaluation of GS-9160, a Novel Inhibitor of Human Immunodeficiency Virus Type 1 Integrase
AuthorsJones, GS; Yu, F; Zeynalzadegan, A; Hesselgesser, J; Chen, XW; Chen, J; Jin, HL; Kim, CU; Wright, M; Geleziunas, R; Tsiang, M
JournalANTIMICROBIAL AGENTS AND CHEMOTHERAPY
PubMed ID
GS-9160 is a novel and potent inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase (IN) that specifically targets the process of strand transfer. It is an authentic inhibitor of HIV-1 integration, since treatment of infected cells results in an elevation of two-long terminal repeat circles and a decrease of ... More
IL23R and IL12B genes: susceptibility analysis in rheumatoid arthritis
AuthorsVarade, J; Lamas, JR; Rodriguez, L; Fernandez-Arquero, M; Loza-Santamaria, E; Jover, JA; de la Concha, EG; Fernandez-Gutierrez, B; Urcelay, E; Martinez, A
JournalANNALS OF THE RHEUMATIC DISEASES
PubMed ID
Microarray analyses of the effects of NF-κB or PI3K pathway inhibitors on the LPS-induced gene expression profile in RAW264.7 cells Synergistic effects of rapamycin on LPS-induced MMP9-overexpression
AuthorsMendes, SD; Candi, A; Vansteenbrugge, M; Pignon, MR; Bult, H; Boudjeltia, KZ; Munaut, C; Raes, M
JournalCELLULAR SIGNALLING
PubMed ID
Lipopolysaccharide (LPS) activates a broad range of signalling pathways including mainly NF-κB and the MAPK cascade, but recent evidence suggests that LPS stimulation also activates the PI3K pathway. To unravel the specific roles of both pathways in LPS signalling and gene expression profiling, we investigated the effects of different inhibitors ... More
Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans
Previous studies have shown relationships between fatty acid ratios in adipose tissue triacylglycerol (TG), adipocyte size and measures of insulin sensitivity. We hypothesised that variations in adipose tissue de novo lipogenesis (DNL) in relation to adiposity might explain some of these observations. In a cross-sectional study, subcutaneous abdominal adipose tissue ... More
Transcriptional Control of Human Adipose Tissue Blood Flow
AuthorsPerez-Matute, P; Neville, MJ; Tan, GD; Frayn, KN; Karpe, F
JournalObesity
PubMed ID
Adipose tissue is highly vascularized and expresses several genes involved in vasodilatory and vasoconstrictive regulation. We took a transcriptional approach to study the relationships between adipose tissue blood flow (ATBF) and genes involved in vasoactive processes. As ATBF is impaired in obesity, we tested whether body weight interfered with the ... More
Targeting MET transcription as a therapeutic strategy in multiple myeloma
AuthorsPhillip, CJ; Stellrecht, CM; Nimmanapalli, R; Gandhi, V
JournalCANCER CHEMOTHERAPY AND PHARMACOLOGY
PubMed ID
Multiple myeloma ( MM) is an incurable indolent malignancy with an average lifespan of 3 years, underscoring the need for new therapies. Studies have shown that the receptor MET and its ligand hepatocyte growth factor play an important role in proliferation, migration, adhesion, and survival of MM cells. Hence, an ... More
Selection and Characterization of Hepatitis C Virus Replicons Dually Resistant to the Polymerase and Protease Inhibitors HCV-796 and Boceprevir (SCH 503034)
HCV-796 is a nonnucleoside inhibitor of the hepatitis C virus (HCV) nonstructural protein 5B (NS5B) polymerase, and boceprevir is an inhibitor of the NS3 serine protease. The emergence of replicon variants resistant to the combination of HCV-796 and boceprevir was evaluated. Combining the inhibitors greatly reduced the frequency with which ... More
ADP-ribosylation Factor 1 Controls the Activation of the Phosphatidylinositol 3-Kinase Pathway to Regulate Epidermal Growth Factor-dependent Growth and Migration of Breast Cancer Cells
AuthorsBoulay, PL; Cotton, M; Melancon, P; Claing, A
JournalJOURNAL OF BIOLOGICAL CHEMISTRY
PubMed ID
Activation of intracellular signaling pathways by growth factors is one of the major causes of cancer development and progression. Recent studies have demonstrated that monomeric G proteins of the Ras family are key regulators of cell proliferation, migration, and invasion. Using an invasive breast cancer cell lines, we demonstrate that ... More
Common Single-Nucleotide Polymorphisms in DNA Double-Strand Break Repair Genes and Breast Cancer Risk
The proteins involved in homologous recombination are instrumental in the error-free repair of dsDNA breakages, and common germ-line variations in these genes are, therefore, potential candidates for involvement in breast cancer development and progression. We carried out a search for common, low-penetrance susceptibility alleles by tagging the common variation in ... More
Intermittent high glucose concentrations reduce neuronal precursor survival by altering the IGF system: the involvement of the neuroprotective factor DHCR24 (Seladin-1)
The exposure of neurons to high glucose concentrations is considered a determinant of diabetic neuropathy, whereas members of the IGF system are neurotropic factors. Here, we investigated the effects of constant and intermittent high glucose concentrations on IGF1 and IGF-binding proteins (IGFBPs) in human neuroblast long-term cell cultures fetal neuroepithelial ... More
Expression of the proapoptotic protein Bax is reduced in bronchial mucous cells of asthmatic subjects
JournalAMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
PubMed ID
The present studies were designed to determine whether our findings in mice showing that the Bcl-2-associated protein X (Bax), which plays a role in the resolution of allergen-induced mucous cell metaplasia, can be applied to asthma in humans. Immunostaining of autopsy tissues from mild and severe asthmatic subjects showed a ... More
Two deltaC splice-variants have distinct signaling abilities during somitogenesis and midline patterning
AuthorsMara, A; Schroeder, J; Holley, SA
JournalDEVELOPMENTAL BIOLOGY
PubMed ID
Notch signaling is required for many developmental processes, yet differences in the signaling abilities of various Notch ligands are poorly understood. Here, we have isolated a splice variant of the zebrafish Notch ligand deltaC in which the inclusion of the last intron leads to a truncation of the C-terminal 39 ... More
The cellulose synthase gene superfamily and biochemical functions of xylem-specific cellulose synthase-like genes in Populus trichocarpa.
AuthorsSuzuki S; Li L; Sun YH; Chiang VL
JournalPlant Physiology
PubMed ID
Wood from forest trees modified for more cellulose or hemicelluloses could be a major feedstock for fuel ethanol. Xylan and glucomannan are the two major hemicelluloses in wood of angiosperms. However, little is known about the genes and gene products involved in the synthesis of these wood polysaccharides. Using Populus ... More
Gene expression profiles in murine hematopoietic stem cells revisited: analysis of cDNA libraries reveals high levels of translational and metabolic activities.
Gene expression studies from hematopoietic stem cell (HSC) populations purified to variable degrees have defined a set of stemness genes. Unexpectedly, results also hinted toward a HSC chromatin poised in a wide-open state. With the aim of providing a robust tool for further studies into the molecular biology of HSCs, ... More
Stringent regulation of DNA repair during human hematopoietic differentiation: a gene expression and functional analysis.
For the lymphohematopoietic system, maturation-dependent alterations in DNA repair function have been demonstrated. Because little information is available on the regulatory mechanisms underlying these changes, we have correlated the expression of DNA damage response genes and the functional repair capacity of cells at distinct stages of human hematopoietic differentiation. Comparing ... More
Interleukin-6 facilitates lipopolysaccharide-induced disruption in working memory and expression of other proinflammatory cytokines in hippocampal neuronal cell layers.
JournalThe Journal of Neuroscience : the Official Journal of the Society for Neuroscience
PubMed ID
Proinflammatory cytokines inhibit learning and memory but the significance of interleukin-6 (IL-6) in acute cognitive deficits induced by the peripheral innate immune system is not known. To examine the functional role of IL-6 in hippocampus-mediated cognitive impairments associated with peripheral infections, C57BL6/J (IL-6(+/+)) and IL-6 knock-out (IL-6(-/-)) mice were trained ... More
Cathepsin D, a lysosomal protease, regulates ABCA1-mediated lipid efflux.
To identify genes involved in the regulation of plasma high density lipoprotein (HDL) cholesterol (HDL-C) levels, patients with low HDL-C and age- and sex-matched controls (normal HDL-C) were extensively characterized. Comparative transcriptome analysis was carried out in cholesterol-loaded monocyte-derived macrophages from low HDL subjects segregated into groups with or without ... More
PGC-1-related coactivator: immediate early expression and characterization of a CREB/NRF-1 binding domain associated with cytochrome c promoter occupancy and respiratory growth.
PGC-1-related coactivator (PRC) was initially characterized as a transcriptional coactivator that shares structural and functional features with PGC-1alpha. Both coactivators interact with nuclear respiratory factor 1 (NRF-1) and activate NRF-1 target genes required for respiratory chain expression. Here, we establish that PRC belongs to the class of immediate early genes ... More
Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes.
JournalProceedings of the National Academy of Sciences of the United States of America
PubMed ID
The mechanisms regulating activation of monocytes remain incompletely understood. Herein we provide evidence that Kruppel-like factor 2 (KLF2) inhibits proinflammatory activation of monocytes. In vitro, KLF2 expression in monocytes is reduced by cytokine activation or differentiation. Consistent with this observation, KLF2 expression in circulating monocytes is reduced in patients with ... More
Histone H3 lysine 4 dimethylation signals the transcriptional competence of the adiponectin promoter in preadipocytes.
AuthorsMusri MM; Corominola H; Casamitjana R; Gomis R; Parrizas M
JournalThe Journal of Biological Chemistry
PubMed ID
Adipogenesis is regulated by a coordinated cascade of sequence-specific transcription factors and coregulators with chromatin-modifying activities that are between them responsible for the establishment of the gene expression pattern of mature adipocytes. Here we examine the histone H3 post-translational modifications occurring at the promoters of key adipogenic genes during adipocyte ... More
The effect of neurogenin3 deficiency on pancreatic gene expression in embryonic mice.
To understand the molecular mechanisms regulating pancreatic endocrine development and function, pancreatic gene expression was compared between Ngn3-deficient mice and littermate controls on embryonic days 13 and 15. Microarray analysis identified 504 genes with significant differences in expression. Fifty-two of these showed at least twofold reduction in Ngn3 knockouts compared ... More
Genome-wide functional analysis of human cell-cycle regulators.
AuthorsMukherji M; Bell R; Supekova L; Wang Y; Orth AP; Batalov S; Miraglia L; Huesken D; Lange J; Martin C; Sahasrabudhe S; Reinhardt M; Natt F; Hall J; Mickanin C; Labow M; Chanda SK; Cho CY; Schultz PG
JournalProceedings of the National Academy of Sciences of the United States of America
PubMed ID
Human cells have evolved complex signaling networks to coordinate the cell cycle. A detailed understanding of the global regulation of this fundamental process requires comprehensive identification of the genes and pathways involved in the various stages of cell-cycle progression. To this end, we report a genome-wide analysis of the human ... More
Characterization of a new NIH-registered variant human embryonic stem cell line, BG01V: a tool for human embryonic stem cell research.
Human embryonic stem cells (hESCs) offer a renewable source of a wide range of cell types for use in research and cell-based therapies. Characterizing these cells provides important information about their current state and affords relevant details for subsequent manipulations. For example, identifying genes expressed during culture, as well as ... More
Silencing of bidirectional promoters by DNA methylation in tumorigenesis.
CpG island methylation within promoters is known to silence individual genes in cancer. The involvement of this process in silencing gene pairs controlled by bidirectional promoters is unclear. In a screen for hypermethylated CpG islands in cancer, bidirectional promoters constituted 25.2% of all identified promoters, which matches with the genomic ... More
Gene expression profiles of peripheral blood leukocytes after endotoxin challenge in humans.
AuthorsTalwar S; Munson PJ; Barb J; Fiuza C; Cintron AP; Logun C; Tropea M; Khan S; Reda D; Shelhamer JH; Danner RL; Suffredini AF
JournalPhysiological Genomics
PubMed ID
To define gene expression profiles that occur during the initial activation of human innate immunity, we administered intravenous endotoxin (n = 8) or saline (n = 4) to healthy subjects and hybridized RNA from blood mononuclear cells (0, 0.5, 6, 24, 168 h) or whole blood (0, 3, 6, 24, ... More
The comparative roles of suppressor of cytokine signaling-1 and -3 in the inhibition and desensitization of cytokine signaling.
AuthorsWormald S; Zhang JG; Krebs DL; Mielke LA; Silver J; Alexander WS; Speed TP; Nicola NA; Hilton DJ
JournalThe Journal of Biological Chemistry
PubMed ID
Negative feedback is a mechanism commonly employed in biological processes as a means of maintaining homeostasis. We have investigated the roles of suppressor of cytokine signaling (SOCS) proteins in regulating the kinetics of negative feedback in response to cytokine signaling. In mouse livers and bone marrow-derived macrophages, both interferon-gamma (IFNgamma) ... More
Testing the importance of p27 degradation by the SCFskp2 pathway in murine models of lung and colon cancer.
JournalProceedings of the National Academy of Sciences of the United States of America
PubMed ID
Decreased expression of the CDK inhibitor p27kip1 in human tumors directly correlates with increased resistance to chemotherapies, increased rates of metastasis, and an overall increased rate of patient mortality. It is thought that decreased p27 expression in tumors is caused by increased proteasomal turnover, in particular activation of the pathway ... More
A novel mechanism of tissue inhibitor of metalloproteinases-1 activation by interleukin-1 in primary human astrocytes.
AuthorsWilczynska KM; Gopalan SM; Bugno M; Kasza A; Konik BS; Bryan L; Wright S; Griswold-Prenner I; Kordula T
JournalThe Journal of Biological Chemistry
PubMed ID
Reactive astrogliosis is the gliotic response to brain injury with activated astrocytes and microglia being the major effector cells. These cells secrete inflammatory cytokines, proteinases, and proteinase inhibitors that influence extracellular matrix (ECM) remodeling. In astrocytes, the expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) is up-regulated by interleukin-1 (IL-1), which ... More
Unique gene expression and hepatocellular injury in the lipopolysaccharide-ranitidine drug idiosyncrasy rat model: comparison with famotidine.
AuthorsLuyendyk JP; Lehman-McKeeman LD; Nelson DM; Bhaskaran VM; Reilly TP; Car BD; Cantor GH; Maddox JF; Ganey PE; Roth RA
JournalToxicological Sciences : An Official Journal of the Society of Toxicology
PubMed ID
Rats cotreated with lipopolysaccharide (LPS) and ranitidine (RAN) but not LPS and famotidine (FAM) develop hepatocellular injury in an animal model of idiosyncratic drug reactions. Evaluation of liver gene expression in rats given LPS and/or RAN led to confirmation that the hemostatic system, hypoxia, and neutrophils (PMNs) are critical mediators ... More
p53 mediates nontranscriptional cell death in dopaminergic cells in response to proteasome inhibition.
Proteasome dysfunction has been demonstrated in Parkinson disease (PD), and proteasome inhibitors have been shown to induce degeneration of dopaminergic neurons in vitro and in vivo. The mechanism whereby proteasome dysfunction leads to dopaminergic cell death, however, is unknown. In this study, we show that proteasome inhibition in both PC12 ... More
Synergistic antitumor activity of ZD6474, an inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling, with gemcitabine and ionizing radiation against pancreatic cancer.
AuthorsBianco C; Giovannetti E; Ciardiello F; Mey V; Nannizzi S; Tortora G; Troiani T; Pasqualetti F; Eckhardt G; de Liguoro M; Ricciardi S; Del Tacca M; Raben D; Cionini L; Danesi R
JournalClinical Cancer Research : An Official Journal of the American Association for Cancer Research
PubMed ID
PURPOSE: Standard treatments have modest effect against pancreatic cancer, and current research focuses on agents targeting molecular pathways involved in tumor growth and angiogenesis. This study investigated the interactions between ZD6474, an inhibitor of tyrosine kinase activities of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor (EGFR), gemcitabine, ... More
Type I interferons produced by hematopoietic cells protect mice against lethal infection by mammalian reovirus.
We defined the function of type I interferons (IFNs) in defense against reovirus strain type 1 Lang (T1L), which is a double-stranded RNA virus that infects Peyer's patches (PPs) after peroral inoculation of mice. T1L induced expression of mRNA for IFN-alpha, IFN-beta, and Mx-1 in PPs and caused localized intestinal ... More
Optimization procedure for small interfering RNA transfection in a 384-well format.
AuthorsBorawski J; Lindeman A; Buxton F; Labow M; Gaither LA
JournalJournal of Biomolecular Screening : the Official Journal of the Society for Biomolecular Screening
PubMed ID
High-throughput screening of RNAi libraries has become an essential part of functional analysis in academic and industrial settings. The transition of a cell-based RNAi assay into a 384-well format requires several optimization steps to ensure the phenotype being screened is appropriately measured and that the signal-to-background ratio is above a ... More
Angiotensin II inhibits the ROMK-like small conductance K channel in renal cortical collecting duct during dietary potassium restriction.
AuthorsWei Y; Zavilowitz B; Satlin LM; Wang WH
JournalThe Journal of Biological Chemistry
PubMed ID
Base-line urinary potassium secretion in the distal nephron is mediated by small conductance rat outer medullary K (ROMK)-like channels. We used the patch clamp technique applied to split-open cortical collecting ducts (CCDs) isolated from rats fed a normal potassium (NK) or low potassium (LK) diet to test the hypothesis that ... More
Four SNPs on chromosome 9p21 in a South Korean population implicate a genetic locus that confers high cross-race risk for development of coronary artery disease.
AuthorsShen GQ; Li L; Rao S; Abdullah KG; Ban JM; Lee BS; Park JE; Wang QK
JournalArteriosclerosis, Thrombosis, and Vascular Biology
PubMed ID
OBJECTIVE: Recent genome-wide association studies have identified 4 SNPs on chromosome 9p21 associated with CAD (rs10757274 and rs2383206) and myocardial infarction (MI: rs2383207 and rs10757278) in White populations in Northern Europe and North America. We aimed to determine whether this locus confers significant susceptibility to CAD in a South Korean ... More
Insulin secretion is increased in pancreatic islets of neuropeptide Y-deficient mice.
Neuropeptide Y (NPY), whose role in appetite regulation is well known, is also expressed in pancreatic islets. Although previous studies indicated that application of NPY to pancreatic islets inhibits insulin secretion, its physiological role in the regulation of insulin secretion is not fully understood. We hypothesized that NPY in islets ... More
Reparative myocardial mechanisms in adult C57BL/6 and MRL mice following injury.
AuthorsNaseem RH; Meeson AP; Michael Dimaio J; White MD; Kallhoff J; Humphries C; Goetsch SC; De Windt LJ; Williams MA; Garry MG; Garry DJ
JournalPhysiological Genomics
PubMed ID
Previous studies have suggested that the heart may be capable of limited repair and regeneration in response to a focal injury, while other studies indicate that the mammalian heart has no regenerative capacity. To further explore this issue, we performed a series of superficial and transmural myocardial injuries in C57BL/6 ... More
Candidate genes controlling pulmonary function in mice: transcript profiling and predicted protein structure.
Impaired development and reduced lung capacity are risk factors of asthma and chronic obstructive pulmonary disease. Previously, our genomewide linkage analysis of C3H/HeJ (C3H) and JF1/Msf (JF1) mouse strains identified quantitative trait loci (QTLs) associated with the complex traits of dead space volume (Vd), total lung capacity (TLC), lung compliance ... More
Ataxin-2 interacts with the DEAD/H-box RNA helicase DDX6 and interferes with P-bodies and stress granules.
AuthorsNonhoff U; Ralser M; Welzel F; Piccini I; Balzereit D; Yaspo ML; Lehrach H; Krobitsch S
JournalMolecular Biology of the Cell
PubMed ID
Tight control of translation is fundamental for eukaryotic cells, and deregulation of proteins implicated contributes to numerous human diseases. The neurodegenerative disorder spinocerebellar ataxia type 2 is caused by a trinucleotide expansion in the SCA2 gene encoding a lengthened polyglutamine stretch in the gene product ataxin-2, which seems to be ... More
Erasure of cellular memory by fusion with pluripotent cells.
AuthorsTae Do J; Han DW; Gentile L; Sobek-Klocke I; Stehling M; Lee HT; Scholer HR
JournalStem Cells (Dayton, Ohio)
PubMed ID
Pluripotent cells have been suggested as a prime source to reprogram somatic cells. We used F9 EC cells as a pluripotent partner to reprogram neurosphere cells (NSCs) because they exhibit a nonneural differentiation potential in the presence of retinoic acid. F9-NSC hybrid cells displayed various features of reprogramming, such as ... More
Characterizing tumor-promoting T cells in chemically induced cutaneous carcinogenesis.
AuthorsRoberts SJ; Ng BY; Filler RB; Lewis J; Glusac EJ; Hayday AC; Tigelaar RE; Girardi M
JournalProceedings of the National Academy of Sciences of the United States of America
PubMed ID
There is a longstanding but poorly understood epidemiologic link between inflammation and cancer. Consistent with this, we previously showed that alphabeta T cell deficiency can increase resistance to chemical carcinogenesis initiated by 7,12-dimethylbenz[a]anthracene and promoted by phorbol 12-myristate 13-acetate. This provoked the hypothesis that alphabeta T cell deficiency removed T ... More
Macrophages are important determinants of acute ocular HSV-1 infection in immunized mice.
AuthorsMott K; Brick DJ; van Rooijen N; Ghiasi H
JournalInvestigative Ophthalmology & Visual Science
PubMed ID
PURPOSE: To determine the effect of macrophage depletion on herpes simplex virus type (HAV)-1 replication in the eye and on the establishment of latency in trigeminal ganglia (TG) of immunized and ocularly infected mice. METHODS: BALB/c mice were immunized with five HSV-1 glycoprotein DNA genes or were sham immunized. The ... More
Identification and characterization of human cdc7 nuclear retention and export sequences in the context of chromatin binding.
AuthorsKim BJ; Kim SY; Lee H
JournalThe Journal of Biological Chemistry
PubMed ID
The Cdc7 serine/threonine kinase activates the initiation of DNA replication by phosphorylating MCM proteins that are bound to the origins of DNA replication. We reported previously that human Cdc7 nuclear import is mediated directly by importin-beta through its binding to the Cdc7 nuclear localization sequence (NLS). Here, we report that ... More
Relations of adipose tissue CIDEA gene expression to basal metabolic rate, energy restriction, and obesity: population-based and dietary intervention studies.
JournalThe Journal of Clinical Endocrinology and Metabolism
PubMed ID
CONTEXT: Cell death-inducing DNA fragmentation factor-alpha-like effector A (CIDEA) could be a potential target for the treatment of obesity via the modulation of metabolic rate, based on the findings that CIDEA inhibits the brown adipose tissue uncoupling process in rodents. OBJECTIVES: Our objects were to investigate the putative link between ... More
Expression of the CTCF-paralogous cancer-testis gene, brother of the regulator of imprinted sites (BORIS), is regulated by three alternative promoters modulated by CpG methylation and by CTCF and p53 transcription factors.
BORIS, like other members of the 'cancer/testis antigen' family, is normally expressed in testicular germ cells and repressed in somatic cells, but is aberrantly activated in cancers. To understand regulatory mechanisms governing human BORIS expression, we characterized its 5'-flanking region. Using 5' RACE, we identified three promoters, designated A, B ... More
Nuclear pregnane X receptor cross-talk with FoxA2 to mediate drug-induced regulation of lipid metabolism in fasting mouse liver.
AuthorsNakamura K; Moore R; Negishi M; Sueyoshi T
JournalThe Journal of Biological Chemistry
PubMed ID
Upon drug activation, the nuclear pregnane X receptor (PXR) regulates not only hepatic drug but also energy metabolism. Using Pxr(-/-) mice, we have now investigated the PXR-mediated repression of lipid metabolism in the fasting livers. Treatment with PXR activator pregnenolone 16alpha-carbonitrile (PCN) down-regulated the mRNA levels of carnitine palmitoyltransferase 1A ... More
R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6.
AuthorsBinnerts ME; Kim KA; Bright JM; Patel SM; Tran K; Zhou M; Leung JM; Liu Y; Lomas WE 3rd; Dixon M; Hazell SA; Wagle M; Nie WS; Tomasevic N; Williams J; Zhan X; Levy MD; Funk WD; Abo A
JournalProceedings of the National Academy of Sciences of the United States of America
PubMed ID
The R-Spondin (RSpo) family of secreted proteins act as potent activators of the Wnt/beta-catenin signaling pathway. We have previously shown that RSpo proteins can induce proliferative effects on the gastrointestinal epithelium in mice. Here we provide a mechanism whereby RSpo1 regulates cellular responsiveness to Wnt ligands by modulating the cell-surface ... More
Up-regulation of loricrin expression by cell adhesion molecule nectin-1 through Rap1-ERK signaling in keratinocytes.
AuthorsWakamatsu K; Ogita H; Okabe N; Irie K; Tanaka-Okamoto M; Ishizaki H; Ishida-Yamamoto A; Iizuka H; Miyoshi J; Takai Y
JournalThe Journal of Biological Chemistry
PubMed ID
Nectin is an immunoglobulin-like cell-cell adhesion molecule, which plays essential roles in the initial step of formation of adherens junctions and tight junctions. We demonstrate here the role of nectin-1 in the epidermis using nectin-1-/- mice. Newborn nectin-1-/- pups showed shiny and slightly reddish skin; the amount of loricrin, one ... More
The thymus is similar to the testis in its pattern of circadian clock gene expression.
AuthorsAlvarez JD; Sehgal A
JournalJournal of Biological Rhythms
PubMed ID
The molecular basis for the circadian clock in mammals consists of a number of genes and proteins that form transcription-translation feedback loops. These loops result in a 24-h rhythm in the expression of mRNA and protein levels. Although the anatomical site of the central circadian clock is the SCN of ... More
Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice.
AuthorsGustavsson N; Lao Y; Maximov A; Chuang JC; Kostromina E; Repa JJ; Li C; Radda GK; Sudhof TC; Han W
JournalProceedings of the National Academy of Sciences of the United States of America
PubMed ID
Vertebrates express at least 15 different synaptotagmins with the same domain structure but diverse localizations and tissue distributions. Synaptotagmin-1,-2, and -9 act as calcium sensors for the fast phrase of neurotransmitter release, and synaptotagmin-12 acts as a calcium-independent modulator of release. The exact functions of the remaining 11 synaptotagmins, however, ... More
Transcriptome analysis of bull semen with extreme nonreturn rate: use of suppression-subtractive hybridization to identify functional markers for fertility.
AuthorsLalancette C; Thibault C; Bachand I; Caron N; Bissonnette N
JournalBiology of Reproduction
PubMed ID
Spermatozoa are terminally differentiated cells produced during the complex process of spermatogenesis. Although the role of their residual RNA content is still being debated, this transcriptome may represent a fingerprint of spermatogenesis quality. In the present study, we undertook differential transcript profiling of spermatozoa from fertile bulls with extreme nonreturn ... More
Differential transport and local translation of cytoskeletal, injury-response, and neurodegeneration protein mRNAs in axons.
AuthorsWillis D; Li KW; Zheng JQ; Chang JH; Smit A; Kelly T; Merianda TT; Sylvester J; van Minnen J; Twiss JL
JournalThe Journal of Neuroscience : the Official Journal of the Society for Neuroscience
PubMed ID
Recent studies have begun to focus on the signals that regulate axonal protein synthesis and the functional significance of localized protein synthesis. However, identification of proteins that are synthesized in mammalian axons has been mainly based on predictions. Here, we used axons purified from cultures of injury-conditioned adult dorsal root ... More
Cell-free cloning of highly expanded CTG repeats by amplification of dimerized expanded repeats.
AuthorsOsborne RJ; Thornton CA
JournalNucleic Acids Research
PubMed ID
We describe conditions for producing uninterrupted expanded CTG repeats consisting of up to 2000 repeats using 29 DNA polymerase. Previously, generation of such repeats was hindered by CTG repeat instability in plasmid vectors maintained in Escherichia coli and poor in vitro ligation of CTG repeat concatemers due to strand slippage. ... More
Mapping of multidrug resistance gene 1 and multidrug resistance-associated protein isoform 1 to 5 mRNA expression along the human intestinal tract.
JournalDrug Metabolism and Disposition: the Biological Fate of Chemicals
PubMed ID
Efflux transporters such as P-glycoprotein and multidrug resistance-associated proteins (MRPs) in the intestinal wall restrict intestinal drug transport. To overcome this limitation for enteral drug absorption, galenical targeting approaches have been proposed for site-specific luminal drug release in segments of the gut, where expression of the respective absorption-limiting transporter is ... More
Interdependent serotonin transporter and receptor pathways regulate S100A4/Mts1, a gene associated with pulmonary vascular disease.
Heightened expression of the S100 calcium-binding protein, S100A4/Mts1, is observed in pulmonary vascular disease. Loss of serotonin (5-hydroxytryptamine [5-HT]) receptors or of the serotonin transporter (SERT) attenuates pulmonary hypertension in animals, and polymorphisms causing gain of SERT function are linked to clinical pulmonary vascular disease. Because 5-HT induces release of ... More
Selective up-regulation of LXR-regulated genes ABCA1, ABCG1, and APOE in macrophages through increased endogenous synthesis of 24(S),25-epoxycholesterol.
Liver X receptor (LXR) activation represents a mechanism to prevent macrophage foam cell formation. Previously, we demonstrated that partial inhibition of oxidosqualene:lanosterol cyclase (OSC) stimulated synthesis of the LXR agonist 24(S),25-epoxycholesterol (24(S),25-epoxy) and enhanced ABCA1-mediated cholesterol efflux. In contrast to a synthetic, nonsteroidal LXR activator, TO-901317, triglyceride accumulation was not ... More
Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion.
AuthorsFujino T; Asaba H; Kang MJ; Ikeda Y; Sone H; Takada S; Kim DH; Ioka RX; Ono M; Tomoyori H; Okubo M; Murase T; Kamataki A; Yamamoto J; Magoori K; Takahashi S; Miyamoto Y; Oishi H; Nose M; Okazaki M; Usui S; Imaizumi K; Yanagisawa M; Sakai J; Yamamoto TT
JournalProceedings of the National Academy of Sciences of the United States of America
PubMed ID
A Wnt coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) plays an essential role in bone accrual and eye development. Here, we show that LRP5 is also required for normal cholesterol and glucose metabolism. The production of mice lacking LRP5 revealed that LRP5 deficiency led to increased plasma cholesterol levels in ... More
Nuclear import of proinflammatory transcription factors is required for massive liver apoptosis induced by bacterial lipopolysaccharide.
AuthorsLiu D; Li C; Chen Y; Burnett C; Liu XY; Downs S; Collins RD; Hawiger J
JournalThe Journal of Biological Chemistry
PubMed ID
Stimulation of macrophages with lipopolysaccharide (LPS) leads to the production of cytokines that elicit massive liver apoptosis. We investigated the in vivo role of stress-responsive transcription factors (SRTFs) in this process focusing on the precipitating events that are sensitive to a cell-permeant peptide inhibitor of SRTF nuclear import (cSN50). In ... More
Human cytomegalovirus-encoded interleukin-10 homolog inhibits maturation of dendritic cells and alters their functionality.
AuthorsChang WL; Baumgarth N; Yu D; Barry PA
JournalJournal of Virology
PubMed ID
Interleukin-10 (IL-10) suppresses the maturation and cytokine production of dendritic cells (DCs), key regulators of adaptive immunity, and prevents the activation and polarization of naive T cells towards protective gamma interferon-producing effectors. We hypothesized that human cytomegalovirus (HCMV) utilizes its viral IL-10 homolog (cmvIL-10) to attenuate DC functionality, thereby subverting ... More
Molecular analysis of survivin isoforms: evidence that alternatively spliced variants do not play a role in mitosis.
Survivin is a protein with proposed roles in cell division and apoptosis. Transcripts encoding splice variants of human survivin have been described and their expression correlated with cancer progression. As survivin forms homodimers in vitro, it has been suggested that these isoforms could interfere with wild type function by forming ... More
Balanced-PCR amplification allows unbiased identification of genomic copy changes in minute cell and tissue samples.
AuthorsWang G; Brennan C; Rook M; Wolfe JL; Leo C; Chin L; Pan H; Liu WH; Price B; Makrigiorgos GM
JournalNucleic Acids Research
PubMed ID
Analysis of genomic DNA derived from cells and fresh or fixed tissues often requires whole genome amplification prior to microarray screening. Technical hurdles to this process are the introduction of amplification bias and/or the inhibitory effects of formalin fixation on DNA amplification. Here we demonstrate a balanced-PCR procedure that allows ... More
microRNAs exhibit high frequency genomic alterations in human cancer.
JournalProceedings of the National Academy of Sciences of the United States of America
PubMed ID
MicroRNAs (miRNAs) are endogenous noncoding RNAs, which negatively regulate gene expression. To determine genomewide miRNA DNA copy number abnormalities in cancer, 283 known human miRNA genes were analyzed by high-resolution array-based comparative genomic hybridization in 227 human ovarian cancer, breast cancer, and melanoma specimens. A high proportion of genomic loci ... More
Effect of apolipoprotein E on the cerebral load of latent herpes simplex virus type 1 DNA.
AuthorsBurgos JS; Ramirez C; Sastre I; Valdivieso F
JournalJournal of Virology
PubMed ID
Herpes simplex virus type 1 (HSV-1) is neurotropic and enters a latent state lasting the lifetime of the host. This pathogen has recently been proposed as a risk factor for Alzheimer's disease (AD) in conjunction with apolipoprotein E4 (ApoE4). In a murine acute infection model, we showed that viral neuroinvasiveness ... More
A Thr357 to Ser polymorphism in homozygous and compound heterozygous subjects causes absent or reduced P2X7 function and impairs ATP-induced mycobacterial killing by macrophages.
The P2X(7) receptor is a ligand-gated cation channel that is highly expressed on mononuclear leukocytes and that mediates ATP-induced apoptosis and killing of intracellular pathogens. There is a wide variation in P2X(7) receptor function between subjects, explained in part by four loss-of-function polymorphisms (R307Q, E496A, I568N, and a 5'-intronic splice ... More
A mutation in the nerve growth factor beta gene (NGFB) causes loss of pain perception.
Identification of genes associated with pain insensitivity syndromes can increase the understanding of the pathways involved in pain and contribute to the understanding of how sensory pathways relate to other neurological functions. In this report we describe the mapping and identification of the gene responsible for loss of deep pain ... More
Patterns of gene expression that characterize long-term survival in advanced stage serous ovarian cancers.
AuthorsBerchuck A; Iversen ES; Lancaster JM; Pittman J; Luo J; Lee P; Murphy S; Dressman HK; Febbo PG; West M; Nevins JR; Marks JR
JournalClinical Cancer Research : An Official Journal of the American Association for Cancer Research
PubMed ID
PURPOSE: A better understanding of the underlying biology of invasive serous ovarian cancer is critical for the development of early detection strategies and new therapeutics. The objective of this study was to define gene expression patterns associated with favorable survival. EXPERIMENTAL DESIGN: RNA from 65 serous ovarian cancers was analyzed ... More
Multiple roles for the receptor tyrosine kinase axl in tumor formation.
A focus of contemporary cancer therapeutic development is the targeting of both the transformed cell and the supporting cellular microenvironment. Cell migration is a fundamental cellular behavior required for the complex interplay between multiple cell types necessary for tumor development. We therefore developed a novel retroviral-based screening technology in primary ... More
Identification of hair cycle-associated genes from time-course gene expression profile data by using replicate variance.
AuthorsLin KK; Chudova D; Hatfield GW; Smyth P; Andersen B
JournalProceedings of the National Academy of Sciences of the United States of America
PubMed ID
The hair-growth cycle is an example of a cyclic process that is well characterized morphologically but understood incompletely at the molecular level. As an initial step in discovering regulators in hair-follicle morphogenesis and cycling, we used DNA microarrays to profile mRNA expression in mouse back skin from eight representative time ... More
Genome-wide protective response used by group A Streptococcus to evade destruction by human polymorphonuclear leukocytes.
JournalProceedings of the National Academy of Sciences of the United States of America
PubMed ID
Group A Streptococcus (GAS) evades polymorphonuclear leukocyte (PMN) phagocytosis and killing to cause human disease, including pharyngitis and necrotizing fasciitis (flesh-eating syndrome). We show that GAS genes differentially regulated during phagocytic interaction with human PMNs comprise a global pathogen-protective response to innate immunity. GAS prophage genes and genes involved in ... More
Induction of Id1 and Id3 by latent membrane protein 1 of Epstein-Barr virus and regulation of p27/Kip and cyclin-dependent kinase 2 in rodent fibroblast transformation.
AuthorsEverly DN Jr; Mainou BA; Raab-Traub N
JournalJournal of Virology
PubMed ID
Latent membrane protein 1 (LMP1), the Epstein-Barr virus oncoprotein, activates NF-kappaB, phosphatidylinositol 3-kinase, mitogen-activated protein kinase, and c-Jun N-terminal kinase signaling. To determine global transcriptional changes induced by LMP1 in epithelial cells, genomic analysis of C33A cells stably expressing LMP1 was performed. Relatively few genes were induced by LMP1. Expression ... More
Mitogen- and stress-activated protein kinase 1 is activated in lesional psoriatic epidermis and regulates the expression of pro-inflammatory cytokines.
Mitogen- and stress-activated protein kinase 1 (MSK1) is a downstream target of both the p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinases (MAPKs). MSK1 stimulates transcription of different pro-inflammatory genes through activation of transcription factors. The purpose of this study was to investigate the expression and activation of ... More
Molecular signature of CD34(+) hematopoietic stem and progenitor cells of patients with CML in chronic phase.
JournalLeukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.k
PubMed ID
In this study, we provide a molecular signature of highly enriched CD34+ cells from bone marrow of untreated patients with chronic myelogenous leukemia (CML) in chronic phase in comparison with normal CD34+ cells using microarrays covering 8746 genes. Expression data reflected several BCR-ABL-induced effects in primary CML progenitors, such as ... More
An analysis of select pathogenic messages in lesional and non-lesional psoriatic skin using non-invasive tape harvesting.
We report the use of non-invasive tape stripping to sample psoriatic lesional and non-lesional skin in 96 patients. The procedure was well tolerated with any discomfort described as mild; we did not observe any cases of Koebner phenomena at any non-lesional tape-stripped sites. Tape-harvested epidermis was extracted for RNA, which ... More
Glycogen Synthase Kinase 3β Is a Novel Regulator of High Glucose- and High Insulin-induced Extracellular Matrix Protein Synthesis in Renal Proximal Tubular Epithelial Cells
AuthorsMariappan, MM; Shetty, M; Sataranatarajan, K; Choudhury, GG; Kasinath, BS
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PubMed ID
'High glucose (30 mM) and high insulin (1 nM), pathogenic factors of type 2 diabetes, increased mRNA expression and synthesis of laminin β1 and fibronectin after 24 h of incubation in kidney proximal tubular epithelial (MCT) cells. We tested the hypothesis that inactivation of glycogen synthase kinase 3β(GSK3β) by high ... More
Effect of high-fat diet on glucose homeostasis and gene expression in glucokinase knockout mice
'Aim: We have generated a heterozygous glucokinase knockout mouse (gk(del/wt)), upon which we investigated the effect of high-fat diet (HFD) with respect to metabolic control and both hepatic and β-cell gene expression. We also investigated the in vitro efficacy of a glucokinase activator (GKA) on glucose-stimulated insulin secretion (GSIS) in ... More
Red Light-induced Systemic Disease Resistance against Root-knot Nematode Meloidogyne javanica and Pseudomonas syringae pv. tomato DC 3000
AuthorsIslam, SZ; Babadoost, M; Bekal, S; Lambert, K
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PubMed ID
'The pretreatment of Arabidopsis with red light (600-700 nm) induces systemic resistance against root-knot nematode Meloidogyne javanica and Pseudomonas syringae pv. tomato DC 3000. Red light treatment significantly (P = 0.05) reduced the number of root galls in both wild type (Col-0) and nahG-expressing Arabidopsis compared with those of white ... More
mRNA stability changes precede changes in steady-state mRNA amounts during hyperosmotic stress
AuthorsMolin, C; Jauhiainen, A; Warringer, J; Nerman, O; Sunnerhagen, P
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PubMed ID
'Under stress, cells need to optimize the activity of a wide range of gene products during the response phases: shock, adaptation, and recovery. This requires coordination of several levels of regulation, including turnover and translation efficiencies of mRNAs. Mitogen-activated protein (MAP) kinase pathways are implicated in many aspects of the ... More
Eukaryotic initiation factor 6 is rate-limiting in translation, growth and transformation
'Cell growth and proliferation require coordinated ribosomal biogenesis and translation. Eukaryotic initiation factors ( eIFs) control translation at the rate- limiting step of initiation(1,2). So far, only two eIFs connect extracellular stimuli to global translation rates(3): eIF4E acts in the eIF4F complex and regulates binding of capped messenger RNA to ... More
Colocalization of Somatic and Meiotic Double Strand Breaks Near the Myc Oncogene on Mouse Chromosome 15
AuthorsNg, SH; Maas, SA; Petkov, PM; Mills, KD; Paigen, K
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PubMed ID
'Both somatic and meiotic recombinations involve the repair of DNA double strand breaks (DSBs) that occur at preferred locations in the genome. Improper repair of DSBs during either mitosis or meiosis can lead to mutations, chromosomal aberration such as translocations, cancer, and/or cell death. Currently, no model exists that explains ... More
A histone methyltransferase modulates antigenic variation in African trypanosomes
AuthorsFigueiredo, LM; Janzen, CJ; Cross, GAM
Journal
PubMed ID
'To evade the host immune system, several pathogens periodically change their cell-surface epitopes. In the African trypanosomes, antigenic variation is achieved by tightly regulating the expression of a multigene family encoding a large repertoire of variant surface glycoproteins (VSGs). Immune evasion relies on two important features: exposing a single type ... More
Gene expression profile of the third pharyngeal pouch reveals role of mesenchymal MafB in embryonic thymus development
AuthorsSultana, DA; Tomita, S; Hamada, M; Iwanaga, Y; Kitahama, Y; Van Khang, N; Hirai, S; Ohigashi, I; Nitta, S; Amagai, T; Takahashi, S; Takahama, Y
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'The thymus provides a microenvironment that induces the differentiation of T-progenitor cells into functional T cells and that establishes a diverse yet self-tolerant T-cell repertoire. However, the mechanisms that lead to the development of the thymus are incompletely understood. We report herein the results of screening for genes that are ... More
The transcriptome of human cytotoxic T cells: Similarities and disparities among allostimulated CD4(+) CTL, CD8(+) CTL and NK cells
'Transcripts expressed in cytotoxic T lymphocytes (CTL) have mechanistic and diagnostic importance in transplantation. We used microarrays to select CTL-associated transcripts (CATs) expressed in human CD4(+) CTL, CD8(+) CTL and NK cells, excluding transcripts expressed in B cells, monocytes and kidney. This generated three transcript sets: CD4(+)-associated, CD8(+)-associated and NK-associated. ... More
Intermittent hypoxia is an angiogenic inducer for endothelial cells: role of HIF-1
AuthorsToffoli, S; Roegiers, A; Feron, O; Van Steenbrugge, M; Ninane, N; Raes, M; Michiels, C
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PubMed ID
'The presence of hypoxia in tumor and its role in promoting angiogenesis are well-established. Recently, in addition to chronic hypoxia, cycling or intermittent hypoxia has also been demonstrated. However, its role in inducing new blood vessel formation is less clear. This work is aimed to investigate whether intermittent hypoxia can ... More
Complex interactions with several arms of the complement system dictate innate and humoral immunity to adenoviral vectors
'The complement system is known to play critical roles in pathogen identification, initiation of innate immune responses and facilitation of adaptive immune responses. Several studies have suggested that recombinant adenoviruses (rAds) interact with proteins of the complement system within minutes of administration. In this study, we assessed the roles of ... More
Epistatic effect of cholesteryl ester transfer protein and hepatic lipase on serum high-density lipoprotein cholesterol levels.
AuthorsIsaacs A; Aulchenko YS; Hofman A; Sijbrands EJ; Sayed-Tabatabaei FA; Klungel OH; Maitland-van der Zee AH; Stricker BH; Oostra BA; Witteman JC; van Duijn CM
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PubMed ID
'OBJECTIVES: Polymorphisms in the hepatic lipase (LIPC -514C > T) and cholesteryl ester transfer protein (CETP I405V) genes affect high-density lipoprotein cholesterol (HDL-c) levels, but their relationship with cardiovascular disease and their combined effect is unclear. The objectives of the current study were to characterize the effect of the hepatic ... More
Further genetic evidence implicates the vasopressin system in childhood-onset mood disorders
'Studies in both animals and humans advocate a role for the vasopressin (AVP) system in the aetiology of depressive symptoms. Attention has particularly focused on the role of AVP in the overactivation of the hypothalamic-pituitary-adrenal (HPA)-axis in mood disorders. Elevated AVP plasma levels have been found in mood disorder patients, ... More
Transcriptional profiling of sunflower plants growing under low temperatures reveals an extensive down-regulation of gene expression associated with chilling sensitivity.
AuthorsHewezi T; Leger M; El Kayal W; Gentzbittel L
Journal
PubMed ID
'Being able to sow early to maximize the growing season and to escape drought stress has increased the importance of low-temperature tolerance in sunflower. Yet knowledge about the molecular basis of sunflower response to low temperature is still lacking. To address this issue, nylon microarrays containing >8000 putative unigenes were ... More
Palmitate Induces Insulin Resistance in H4IIEC3 Hepatocytes through Reactive Oxygen Species Produced by Mitochondria
'Visceral adiposity in obesity causes excessive free fatty acid (FFA) flux into the liver via the portal vein and may cause fatty liver disease and hepatic insulin resistance. However, because animal models of insulin resistance induced by lipid infusion or a high fat diet are complex and may be accompanied ... More
Association study of 11β-hydroxysteroid dehydrogenase type 1 gene polymorphisms and metabolic syndrome in urban Japanese cohort
'11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1), one of the isoforms of the 11β-hydroxysteroid dehydrogenase enzymes, acts as an oxo-reductase to reactivate cortisone to cortisol, plays a critical role in tissue-specific corticosteroid reactions, and is therefore a key molecule associated with the development of metabolic syndrome. We investigated whether variations in the ... More
Olmesartan ameliorates a dietary rat model of non-alcoholic steatohepatitis through its pleiotropic effects
AuthorsKurita, S; Takamura, T; Ota, T; Matsuzawa-Nagata, N; Kita, Y; Uno, M; Nabemoto, S; Ishikura, K; Misu, H; Ando, H; Zen, Y; Nakanuma, Y; Kaneko, S
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'Insulin resistance is a major pathological condition associated with obesity and metabolic syndrome. Insulin resistance and the renin-angiotensin system are intimately linked. We evaluated the role of the renin-angiotensin system in the pathogenesis of insulin resistance-associated, non-alcoholic steatohepatitis by using the angiotensin II type 1 receptor blocker olmesartan medoxomil in ... More
Red meat and poultry intake, polymorphisms in the nucleotide excision repair and mismatch repair pathways and colorectal cancer risk
'Diets high in red meat have been consistently associated with colorectal cancer (CRC) risk and may result in exposure to carcinogens that cause DNA damage [i.e polycyclic aromatic hydrocarbons, heterocyclic amines (HCAs) and N-nitroso compounds]. Using a family-based study, we investigated whether polymorphisms in the nucleotide excision repair (NER) (ERCC1 ... More
SIRT1 genetic variation and mortality in type 2 diabetes: interaction with smoking and dietary niacin
Authors
Journal
PubMed ID
'SIRT1 protects cells against oxidative stress and aging. Its activity may be modulated by dietary niacin (vitamin 133) intake. We studied the association of SIRT1 genetic variation with mortality in subjects with increased oxidative stress (type 2 diabetes and smokers) in relation to dietary niacin. In 4573 participants from the ... More