Physiological Genomics
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Changes in behavior and gene expression induced by caloric restriction in C57BL/6 mice
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In this study, we investigated two different dieting regimens: repeated fasting and refeeding (RFR) and daily feeding of half the amount of food consumed by RFR mice (CR). CR and RFR mice had an approximate 20% reduction in food intake compared with control mice. Open field, light-dark transition, elevated plus maze, and forced swimming tests indicated that CR, but not RFR, reduced anxiety- and depressive-like behaviors, with a reduction peak on day 8. Using a mouse whole genome microarray, we analyzed gene expression in the prefrontal cortex, amygdala, and hypothalamus. In addition to the CR-responsive genes commonly modi...
Source: Physiological Genomics - November 6, 2009 Category: Genetics & Stem Cells Authors: Yamamoto, Y., Tanahashi, T., Kawai, T., Chikahisa, S., Katsuura, S., Nishida, K., Teshima-Kondo, S., Sei, H., Rokutan, K. Tags: Research Articles Source Type: journals
Evidence of MyomiR network regulation of {beta}-myosin heavy chain gene expression during skeletal muscle atrophy
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The objectives of the current study were to identify miRs expressed in the rat soleus muscle and determine if their expression was changed in response to hindlimb suspension. Comprehensive profiling revealed 151 miRs were expressed in the soleus muscle and expression of 18 miRs were significantly (P < 0.01) changed after 2 and/or 7 days of hindlimb suspension. The significant decrease (16%) in expression of muscle-specific miR-499 in response to hindlimb suspension was confirmed by RT-PCR and suggested activation of the recently proposed miR encoded by myosin gene (MyomiR) network during atrophy. Further analysis of sol...
Source: Physiological Genomics - November 6, 2009 Category: Genetics & Stem Cells Authors: McCarthy, J. J., Esser, K. A., Peterson, C. A., Dupont-Versteegden, E. E. Tags: Research Articles Source Type: journals
miR-290 acts as a physiological effector of senescence in mouse embryo fibroblasts
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The culture-induced senescence of mouse embryo fibroblasts (MEF) correlates with reduction of cell proliferation. In this work we found that the accumulation of cells with 4C DNA content and the transcriptional change of several microRNAs (miRNAs or miRs) are relevant events in culture senescence. By comparing the miRNA expression profiles of physiologically senescent MEF and that of senescent MEF induced by the downregulation of leukemia-related factor, we identified miR-290 as a common upregulated miRNA. When miR-290 was transfected in presenescent MEF, SA-β-gal+ cells and p16, two markers of culture senescence, inc...
Source: Physiological Genomics - November 6, 2009 Category: Genetics & Stem Cells Authors: Pitto, L., Rizzo, M., Simili, M., Colligiani, D., Evangelista, M., Mercatanti, A., Mariani, L., Cremisi, F., Rainaldi, G. Tags: Research Articles Source Type: journals
Transcription profiling and regulation of fat metabolism genes in diapausing adults of the mosquito Culex pipiens
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Culex pipiens, the mosquito that vectors West Nile virus in North America, overwinters in an adult diapause (dormancy) that is programmed by the short day length and low temperatures of autumn. In response to these environmental signals, females cease feeding on blood and instead seek sources of nectar used to generate the huge lipid reserves required for winter survival. To identify regulatory networks that regulate fat accumulation and fat consumption during diapause, we compared expression of fat-related genes from nondiapausing females with expression of those same genes in early and late diapause and at diapause termi...
Source: Physiological Genomics - November 6, 2009 Category: Genetics & Stem Cells Authors: Sim, C., Denlinger, D. L. Tags: Research Articles Source Type: journals
Clinical and molecular characterizations of novel POU3F4 mutations reveal that DFN3 is due to null function of POU3F4 protein
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X-linked deafness type 3 (DFN3), the most prevalent X-linked form of hereditary deafness, is caused by mutations in the POU3F4 locus, which encodes a member of the POU family of transcription factors. Despite numerous reports on clinical evaluations and genetic analyses describing novel POU3F4 mutations, little is known about how such mutations affect normal functions of the POU3F4 protein and cause inner ear malformations and deafness. Here we describe three novel mutations of the POU3F4 gene and their clinical characterizations in three Korean families carrying deafness segregating at the DFN3 locus. The three mutations ...
Source: Physiological Genomics - November 6, 2009 Category: Genetics & Stem Cells Authors: Lee, H. K., Song, M. H., Kang, M., Lee, J. T., Kong, K.-A., Choi, S.-J., Lee, K. Y., Venselaar, H., Vriend, G., Lee, W.-S., Park, H.-J., Kwon, T. K., Bok, J., Kim, U.-K. Tags: Research Articles Source Type: journals
Genomic analyses reveal a conserved glutathione homeostasis pathway in the invertebrate chordate Ciona intestinalis
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This report describes the annotation and expression analysis of genes contributing to GSH homeostasis in the invertebrate chordate Ciona intestinalis. A core pathway comprising 19 genes contributing to the biosynthesis of GSH and its use as both a redox buffer and a conjugate in phase II detoxification as well as known transcriptional regulators were analyzed. These genes exhibit a high level of sequence conservation with corresponding human, rat, and mouse homologs and were expressed constitutively in tissues of adult animals. The GSH biosynthetic genes Gclc and Gclm were also responsive to the prototypical antioxidant te...
Source: Physiological Genomics - November 6, 2009 Category: Genetics & Stem Cells Authors: Nava, G. M., Lee, D. Y., Ospina, J. H., Cai, S.-Y., Gaskins, H. R. Tags: Call for Papers: Comparative Genomics Source Type: journals
Effects of atherogenic diet on hepatic gene expression across mouse strains
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Diets high in fat and cholesterol are associated with increased obesity and metabolic disease in mice and humans. To study the molecular basis of the metabolic response to dietary fat, 10 inbred strains of mice were fed atherogenic high-fat and control low-fat diets. Liver gene expression and whole animal phenotypes were measured and analyzed in both sexes. The effects of diet, strain, and sex on gene expression were determined irrespective of complex processes, such as feedback mechanisms, that could have mediated the genomic responses. Global gene expression analyses demonstrated that animals of the same strain and sex h...
Source: Physiological Genomics - November 6, 2009 Category: Genetics & Stem Cells Authors: Shockley, K. R., Witmer, D., Burgess-Herbert, S. L., Paigen, B., Churchill, G. A. Tags: Call for Papers: Computational Modeling of Physiological Systems Source Type: journals
Embrace diversity! Systems genetics-enabled discovery of disease networks
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(Source: Physiological Genomics)
Source: Physiological Genomics - November 6, 2009 Category: Genetics & Stem Cells Authors: Voy, B. H., Aronow, B. J. Tags: Editorial Focus Source Type: journals
Lack of periostin leads to suppression of Notch1 signaling and calcific aortic valve disease
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The Postn gene encodes protein periostin. During embryonic development, it is highly expressed in the outflow tract (OFT) endocardial cushions of the developing heart, which give rise to several structures of the mature heart including the aortic valve. Periostin was previously implicated in osteoblast differentiation, cancer metastasis, and tooth and bone development, but its role in cardiac OFT development is unclear. To elucidate the role that periostin plays in the developing heart we analyzed cardiac OFT phenotype in mice after deletion of the Postn gene. We found that lack of periostin in the embryonic OFT leads to e...
Source: Physiological Genomics - November 6, 2009 Category: Genetics & Stem Cells Authors: Tkatchenko, T. V., Moreno-Rodriguez, R. A., Conway, S. J., Molkentin, J. D., Markwald, R. R., Tkatchenko, A. V. Tags: Translational Physiology Source Type: journals
Gene expression and muscle fiber function in a porcine ICU model
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Skeletal muscle wasting and impaired muscle function in response to mechanical ventilation and immobilization in intensive care unit (ICU) patients are clinically challenging partly due to 1) the poorly understood intricate cellular and molecular networks and 2) the unavailability of an animal model mimicking this condition. By employing a unique porcine model mimicking the conditions in the ICU with long-term mechanical ventilation and immobilization, we have analyzed the expression profile of skeletal muscle biopsies taken at three time points during a 5-day period. Among the differentially regulated transcripts, extrace...
Source: Physiological Genomics - November 6, 2009 Category: Genetics & Stem Cells Authors: Banduseela, V. C., Ochala, J., Chen, Y.-W., Goransson, H., Norman, H., Radell, P., Eriksson, L. I., Hoffman, E. P., Larsson, L. Tags: Translational Physiology Source Type: journals
Translational informatics: enabling high-throughput research paradigms
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The objective of presenting such findings and constructs is to provide the clinical and translational research community with a common frame of reference for discussing and expanding upon such models and methodologies. (Source: Physiological Genomics)
Source: Physiological Genomics - November 6, 2009 Category: Genetics & Stem Cells Authors: Payne, P. R. O., Embi, P. J., Sen, C. K. Tags: Review Source Type: journals
Transcriptome analysis reveals an unexpected role of a collagen tyrosine kinase receptor gene, Ddr2, as a regulator of ovarian function
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Mice homozygous for the smallie (slie) mutation lack a collagen receptor, discoidin domain receptor 2 (DDR2), and are dwarfed and infertile due to peripheral dysregulation of the endocrine system of unknown etiology. We used a systems biology approach to identify biological networks affected by Ddr2slie/slie mutation in ovaries using microarray analysis and validate findings using molecular, cellular, and functional biological assays. Transcriptome analysis indicated several altered gene categories in Ddr2slie/slie mutants, including gonadal development, ovulation, antiapoptosis, and steroid hormones. Subsequent biological...
Source: Physiological Genomics - October 7, 2009 Category: Genetics & Stem Cells Authors: Matsumura, H., Kano, K., de Evsikova, C. M., Young, J. A., Nishina, P. M., Naggert, J. K., Naito, K. Tags: Research Articles Source Type: journals
Metabolic phenotyping of a model of adipocyte differentiation
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In this study, the metabolic phenotype associated with differentiation of the 3T3-L1 cell line has been studied using gas chromatography-mass spectrometry, 1H nuclear magnetic resonance spectroscopy, liquid chromatography-mass spectrometry, direct infusion-mass spectrometry, and 13C substrate labeling in conjunction with multivariate statistics. The changes in metabolite concentrations at distinct periods during differentiation have been defined including alterations in the TCA cycle, glycolysis, the production of odd chain fatty acids by -oxidation, fatty acid synthesis, fatty acid desaturation, polyamine biosynthesis, an...
Source: Physiological Genomics - October 7, 2009 Category: Genetics & Stem Cells Authors: Roberts, L. D., Virtue, S., Vidal-Puig, A., Nicholls, A. W., Griffin, J. L. Tags: Research Articles Source Type: journals
Transcriptional profiling of human cavernosal endothelial cells reveals distinctive cell adhesion phenotype and role for claudin 11 in vascular barrier function
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To determine specific molecular features of endothelial cells (ECs) relevant to the physiological process of penile erection we compared gene expression of human EC derived from corpus cavernosum of men with and without erectile dysfunction (HCCEC) to coronary artery (HCAEC) and umbilical vein (HUVEC) using Affymetrix GeneChip microarrays and GeneSifter software. Genes differentially expressed across samples were partitioned around medoids to identify genes with highest expression in HCCEC. A total of 190 genes/transcripts were highly expressed only in HCCEC. Gene Ontology classification indicated cavernosal enrichment in ...
Source: Physiological Genomics - October 7, 2009 Category: Genetics & Stem Cells Authors: Wessells, H., Sullivan, C. J., Tsubota, Y., Engel, K. L., Kim, B., Olson, N. E., Thorner, D., Chitaley, K. Tags: Call for Papers: Comparative Genomics Source Type: journals
Discovery of candidate genes and pathways in the endometrium regulating ovine blastocyst growth and conceptus elongation
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This study utilized sheep as a model to identify candidate genes and regulatory networks in the endometrium that govern preimplantation blastocyst growth and development. Ewes were treated daily with either P4 or corn oil vehicle from day 1.5 after mating to either day 9 or day 12 of pregnancy when endometrium was obtained by hysterectomy. Microarray analyses revealed many differentially expressed genes in the endometria affected by day of pregnancy and early P4 treatment. In situ hybridization analyses revealed that many differentially expressed genes were expressed in a cell-specific manner within the endometrium. The Da...
Source: Physiological Genomics - October 7, 2009 Category: Genetics & Stem Cells Authors: Satterfield, M. C., Song, G., Kochan, K. J., Riggs, P. K., Simmons, R. M., Elsik, C. G., Adelson, D. L., Bazer, F. W., Zhou, H., Spencer, T. E. Tags: Call for Papers: Comparative Genomics Source Type: journals
The rocky road toward clinical genetic testing: insights into the physio-genetic basis of hearing loss
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(Source: Physiological Genomics)
Source: Physiological Genomics - October 7, 2009 Category: Genetics & Stem Cells Authors: Runge-Samuelson, C., Olivier, M. Tags: Editorial Focus Source Type: journals
Meta-analysis of gene expression in human pancreatic islets after in vitro expansion
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Pancreatic islet transplantation as a potential cure for type 1 diabetes (T1D) cannot be scaled up due to a scarcity of human pancreas donors. In vitro expansion of β-cells from mature human pancreatic islets provides an alternative source of insulin-producing cells. The exact nature of the expanded cells produced by diverse expansion protocols and their potential for differentiation into functional β-cells remain elusive. We performed a large-scale meta-analysis of gene expression in human pancreatic islet cells, which were processed using three different previously described protocols for expansion and for whic...
Source: Physiological Genomics - September 8, 2009 Category: Genetics & Stem Cells Authors: Kutlu, B., Kayali, A. G., Jung, S., Parnaud, G., Baxter, D., Glusman, G., Goodman, N., Behie, L. A., Hayek, A., Hood, L. Tags: Research Articles Source Type: journals
Transcriptional changes in right ventricular tissues are enriched in the outflow tract compared with the apex during chronic pulmonary embolism in rats
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Moderate to severe pulmonary embolism (PE) can cause pulmonary arterial hypertension and right ventricular (RV) heart damage. Previous studies from our laboratory indicate that the basal outflow tract of the RV is injured and has acute inflammation followed by tissue remodeling while the apex appears normal. The present studies examine transcription responses to chronic PE in RV apex and outflow tracts using DNA microarrays to identify transcription responses by region. Changes predominated in the RV outflow tract (8,575 genes showed ≥1.5-fold expression change). Gene ontology and KEGG analyses indicated a significant d...
Source: Physiological Genomics - September 8, 2009 Category: Genetics & Stem Cells Authors: Zagorski, J., Obraztsova, M., Gellar, M. A., Kline, J. A., Watts, J. A. Tags: Research Articles Source Type: journals
Kininogen gene (KNG) variation has a consistent effect on aldosterone response to antihypertensive drug therapy: the GERA study
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In this study, we investigated aldosterone response to two antihypertensive drugs—a thiazide diuretic and an angiotensin receptor blocker (ARB). Genetic variations in 50 candidate genes were tested for association with aldosterone response in four independent samples: African American (AA) responders to a diuretic (n = 289), AA responders to an ARB (n = 252), European American (EA) responders to a diuretic (n = 295) and EA responders to an ARB (n = 300). Linear regression was used to test the association with inclusion of age, sex, and body mass index as covariates. The results indicated the existence of one or more ...
Source: Physiological Genomics - September 8, 2009 Category: Genetics & Stem Cells Authors: Barbalic, M., Schwartz, G. L., Chapman, A. B., Turner, S. T., Boerwinkle, E. Tags: Research Articles Source Type: journals
Genetic analysis of daily physical activity using a mouse chromosome substitution strain
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There is considerable evidence for a genetic basis underlying individual differences in spontaneous physical activity in humans and animals. Previous publications indicate that the physical activity level and pattern vary among inbred strains of mice and identified a genomic region on chromosome 13 as quantitative trait loci (QTL) for physical activity. To confirm and further characterize the role of chromosome 13 in regulating daily physical activity level and pattern, we conducted a comprehensive phenotypic study in the chromosome 13 substitution strain (CSS-13) in which the individual chromosome 13 from the A/J strain w...
Source: Physiological Genomics - September 8, 2009 Category: Genetics & Stem Cells Authors: Yang, H. S., Vitaterna, M. H., Laposky, A. D., Shimomura, K., Turek, F. W. Tags: Research Articles Source Type: journals
Distinct genetic regulation of progression of diabetes and renal disease in the Goto-Kakizaki rat
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Goto-Kakizaki (GK) rats develop early-onset type 2 diabetes (T2D) symptoms, with signs of diabetic nephropathy becoming apparent with aging. To determine whether T2D and renal disease share similar genetic architecture, we ran a quantitative trait locus (QTL) analysis in the F2 progeny of a GK x Brown Norway (BN) rat cross. Further, to determine whether genetic components change over time, we ran the QTL analysis on phenotypes collected longitudinally, at 3, 6, 9 and 12 mo, from the same animals. We confirmed three chromosomal regions that are linked to early diabetes phenotypes (chromosomes 1, 5, and 10) and a single regi...
Source: Physiological Genomics - September 8, 2009 Category: Genetics & Stem Cells Authors: Nobrega, M. A., Solberg Woods, L. C., Fleming, S., Jacob, H. J. Tags: Research Articles Source Type: journals
Pleiotropic effects of negative energy balance in the postpartum dairy cow on splenic gene expression: repercussions for innate and adaptive immunity
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Increased energy demands to support lactation, coupled with lowered feed intake capacity results in negative energy balance (NEB) and is typically characterized by extensive mobilization of body energy reserves in the early postpartum dairy cow. The catabolism of stored lipid leads to an increase in the systemic concentrations of nonesterified fatty acids (NEFA) and β-hydroxy butyrate (BHB). Oxidation of NEFA in the liver result in the increased production of reactive oxygen species and the onset of oxidative stress and can lead to disruption of normal metabolism and physiology. The immune system is depressed in the p...
Source: Physiological Genomics - September 8, 2009 Category: Genetics & Stem Cells Authors: Morris, D. G., Waters, S. M., McCarthy, S. D., Patton, J., Earley, B., Fitzpatrick, R., Murphy, J. J., Diskin, M. G., Kenny, D. A., Brass, A., Wathes, D. C. Tags: Research Articles Source Type: journals
Gene expression profiles of bovine caruncular and intercaruncular endometrium at implantation
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At implantation the endometrium undergoes modifications necessary for its physical interactions with the trophoblast as well as the development of the conceptus. We aim to identify endometrial factors and pathways essential for a successful implantation in the caruncular (C) and the intercaruncular (IC) areas in cattle. Using a 13,257-element bovine oligonucleotide array, we established expression profiles at day 20 of the estrous cycle or pregnancy (implantation), revealing 446 and 1,295 differentially expressed genes (DEG) in C and IC areas, respectively (false discovery rate = 0.08). The impact of the conceptus was high...
Source: Physiological Genomics - September 8, 2009 Category: Genetics & Stem Cells Authors: Mansouri-Attia, N., Aubert, J., Reinaud, P., Giraud-Delville, C., Taghouti, G., Galio, L., Everts, R. E., Degrelle, S., Richard, C., Hue, I., Yang, X., Tian, X. C., Lewin, H. A., Renard, J.-P., Sandra, O. Tags: Call For Papers: Comparative Genomics Source Type: journals
Negative energy balance alters global gene expression and immune responses in the uterus of postpartum dairy cows
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Most dairy cows suffer uterine microbial contamination postpartum. Persistent endometritis often develops, associated with reduced fertility. We used a model of differential feeding and milking regimes to produce cows in differing negative energy balance status in early lactation (mild or severe, MNEB or SNEB). Blood hematology was assessed preslaughter at 2 wk postpartum. RNA expression in endometrial samples was compared using bovine Affymetrix arrays. Data were mapped using Ingenuity Pathway Analysis. Circulating concentrations of IGF-I remained lower in the SNEB group, whereas blood nonesterified fatty acid and β-...
Source: Physiological Genomics - September 8, 2009 Category: Genetics & Stem Cells Authors: Wathes, D. C., Cheng, Z., Chowdhury, W., Fenwick, M. A., Fitzpatrick, R., Morris, D. G., Patton, J., Murphy, J. J. Tags: Call For Papers: Comparative Genomics Source Type: journals
Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper
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Copper is an essential trace element; however, at supraphysiological levels, it can be extremely toxic. Microarray data from HepG2 cells exposed to 100, 200, 400, and 600 µM copper for 4, 8, 12 and 24 h were generated and analyzed. Principal components, K-means, and hierarchical clustering, interactome, and pathway mapping analyses indicated that these exposure conditions induce physiological and toxicological changes in the HepG2 transcriptome. As a general trend, when the level of toxicity increases, the number and diversity of affected genes, Gene Ontology categories, regulatory pathways, and complexity of interac...
Source: Physiological Genomics - August 6, 2009 Category: Genetics & Stem Cells Authors: Song, M. O., Li, J., Freedman, J. H. Tags: Research Articles Source Type: journals
Lasp1 gene disruption is linked to enhanced cell migration and tumor formation
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Lasp1 is an actin-binding, signaling pathway-regulated phosphoprotein that is overexpressed in several cancers. siRNA knockdown in cell lines retards cell migration, suggesting the possibility that Lasp1 upregulation influences cancer metastasis. Herein, we utilized a recently developed gene knockout model to assess the role of Lasp1 in modulating nontransformed cell functions. Wound healing and tumor initiation progressed more rapidly in Lasp1–/– mice compared with Lasp1+/+ controls. Embryonic fibroblasts (MEFs) derived from Lasp1–/– mice also migrated more rapidly in vitro. These MEFs characterist...
Source: Physiological Genomics - August 6, 2009 Category: Genetics & Stem Cells Authors: Zhang, H., Chen, X., Bollag, W. B., Bollag, R. J., Sheehan, D. J., Chew, C. S. Tags: Research Articles Source Type: journals
Longitudinal system-based analysis of transcriptional responses to type I interferons
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Type I interferons (IFNs) are pleiotropic cytokines that modulate both innate and adaptive immune responses. They have been used to treat autoimmune disorders, cancers, and viral infection and have been demonstrated to elicit differential responses within cells, despite sharing a single receptor. The molecular basis for such differential responses has remained elusive. To identify the mechanisms underlying differential type I IFN signaling, we used whole genome microarrays to measure longitudinal transcriptional events within human CD4+ T cells treated with IFN-2b or IFN-β1a. We identified differentially regulated gen...
Source: Physiological Genomics - August 6, 2009 Category: Genetics & Stem Cells Authors: Pappas, D. J., Coppola, G., Gabatto, P. A., Gao, F., Geschwind, D. H., Oksenberg, J. R., Baranzini, S. E. Tags: Research Articles Source Type: journals
Profiling neuroendocrine gene expression changes following fadrozole-induced estrogen decline in the female goldfish
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Teleost fish represent unique models to study the role of neuroestrogens because of the extremely high activity of brain aromatase (AroB; the product of cyp19a1b). Aromatase respectively converts androstenedione and testosterone to estrone and 17β-estradiol (E2). Specific inhibition of aromatase activity by fadrozole has been shown to impair estrogen production and influence neuroendocrine and reproductive functions in fish, amphibians, and rodents. However, very few studies have identified the global transcriptomic response to fadrozole-induced decline of estrogens in a physiological context. In our study, sexually m...
Source: Physiological Genomics - August 6, 2009 Category: Genetics & Stem Cells Authors: Zhang, D., Popesku, J. T., Martyniuk, C. J., Xiong, H., Duarte-Guterman, P., Yao, L., Xia, X., Trudeau, V. L. Tags: Research Articles Source Type: journals
Skeletal muscle gene expression after myostatin knockout in mature mice
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There is much interest in developing anti-myostatin agents to reverse or prevent muscle atrophy in adults, so it is important to characterize the effects of reducing myostatin activity after normal muscle development. For assessment of the effect of loss of myostatin signaling on gene expression in muscle, RNA from mice with postdevelopmental myostatin knockout was analyzed with oligonucleotide microarrays. Myostatin was undetectable in muscle within 2 wk after Cre recombinase activation in 4-month-old male mice with floxed myostatin genes. Three months after myostatin depletion, muscle mass had increased 26% (vs. 2% after...
Source: Physiological Genomics - August 6, 2009 Category: Genetics & Stem Cells Authors: Welle, S., Cardillo, A., Zanche, M., Tawil, R. Tags: Research Articles Source Type: journals
eIF2{alpha} kinases GCN2 and PERK modulate transcription and translation of distinct sets of mRNAs in mouse liver
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In eukaryotes, selective derepression of mRNA translation through altered utilization of upstream open reading frames (uORF) or internal ribosomal entry sites (IRES) regulatory motifs following exposure to stress is regulated at the initiation stage through the increased phosphorylation of eukaryotic initiation factor 2 on its -subunit (eIF2). While there is only one known eIF2 kinase in yeast, general control nonderepressible 2 (GCN2), mammals have evolved to express at least four: GCN2, heme-regulated inhibitor kinase (HRI), double-stranded RNA-activated protein kinase (PKR), and PKR-like endoplasmic reticulum-resident k...
Source: Physiological Genomics - August 6, 2009 Category: Genetics & Stem Cells Authors: Dang Do, A. N., Kimball, S. R., Cavener, D. R., Jefferson, L. S. Tags: Research Articles Source Type: journals
Microarray profiling reveals CXCR4a is downregulated by blood flow in vivo and mediates collateral formation in zebrafish embryos
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The response to hemodynamic force is implicated in a number of pathologies including collateral vessel development. However, the transcriptional effect of hemodynamic force is extremely challenging to examine in vivo in mammals without also detecting confounding processes such as hypoxia and ischemia. We therefore serially examined the transcriptional effect of preventing cardiac contraction in zebrafish embryos which can be deprived of circulation without experiencing hypoxia since they obtain sufficient oxygenation by diffusion. Morpholino antisense knock-down of cardiac troponin T2 (tnnt2) prevented cardiac contraction ...
Source: Physiological Genomics - August 6, 2009 Category: Genetics & Stem Cells Authors: Packham, I. M., Gray, C., Heath, P. R., Hellewell, P. G., Ingham, P. W., Crossman, D. C., Milo, M., Chico, T. J. A. Tags: Research Articles Source Type: journals
Modulation of the allergic asthma transcriptome following resiquimod treatment
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Resiquimod is a compound belonging to the imidazoquinoline family of compounds known to signal through Toll-like receptor 7. Resiquimod treatment has been demonstrated to inhibit the development of allergen induced asthma in experimental models. The aim of the present study was to elucidate the molecular processes that were altered following resiquimod treatment and allergen challenge in a mouse model of allergic asthma. Employing microarray analysis, we have characterized the "asthmatic" transcriptome of the lungs of A/J and C57BL/6 mice and determined that it includes genes involved in the control of cell cycle progressi...
Source: Physiological Genomics - August 6, 2009 Category: Genetics & Stem Cells Authors: Camateros, P., Kanagaratham, C., Henri, J., Sladek, R., Hudson, T. J., Radzioch, D. Tags: Research Articles Source Type: journals
Large-scale mRNA analysis of female skeletal muscles during 60 days of bed rest with and without exercise or dietary protein supplementation as countermeasures
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Microgravity has a dramatic impact on human physiology, illustrated in particular, with skeletal muscle impairment. A thorough understanding of the mechanisms leading to loss of muscle mass and structural disorders is necessary for defining efficient clinical and spaceflight countermeasures. We investigated the effects of long-term bed rest on the transcriptome of soleus (SOL) and vastus lateralis (VL) muscles in healthy women (BRC group, n = 8), and the potential beneficial impact of protein supplementation (BRN group, n = 8) and of a combined resistance and aerobic training (BRE group, n = 8). Gene expression profiles we...
Source: Physiological Genomics - August 6, 2009 Category: Genetics & Stem Cells Authors: Chopard, A., Lecunff, M., Danger, R., Lamirault, G., Bihouee, A., Teusan, R., Jasmin, B. J., Marini, J. F., Leger, J. J. Tags: Research Articles Source Type: journals
Distinct and novel SLC26A4/Pendrin mutations in Chinese and U.S. patients with nonsyndromic hearing loss
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Mutations of the human SLC26A4/PDS gene constitute the most common cause of syndromic and nonsyndromic hearing loss. Definition of the SLC26A4 mutation spectrum among different populations with sensorineural hearing loss is important for development of optimal genetic screening services for congenital hearing impairment. We screened for SLC26A4 mutations among Chinese and U.S. subjects with hearing loss, using denaturing HPLC (DHPLC) and direct DNA sequencing. Fifty-two of 55 Chinese subjects with deafness accompanied by enlargement of the vestibular aqueduct (EVA) exhibited at least one mutant SLC26A4 allele, whereas SLC2...
Source: Physiological Genomics - August 6, 2009 Category: Genetics & Stem Cells Authors: Dai, P., Stewart, A. K., Chebib, F., Hsu, A., Rozenfeld, J., Huang, D., Kang, D., Lip, V., Fang, H., Shao, H., Liu, X., Yu, F., Yuan, H., Kenna, M., Miller, D. T., Shen, Y., Yang, W., Zelikovic, I., Platt, O. S., Han, D., Alper, S. L., Wu, B.-L. Tags: Translational Physiology Source Type: journals
Stimulation of growth and changes in the hepatic transcriptome by 17{beta}-estradiol in the yellow perch (Perca flavescens)
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The effects of dietary 17β-estradiol (E2) on growth and liver transcriptomics were investigated in the yellow perch (Perca flavescens). After a 3-mo treatment, E2 significantly stimulated an increase in length and weight of juvenile male and female perch relative to control animals. The increase was significantly greater in females compared with males. Separate, unnormalized cDNA libraries were constructed from equal quantities of RNA from 6 male and 6 female livers of E2-treated and control perch, and 3,546 and 3,719 expressed sequence tags (ESTs) were obtained, respectively. To characterize E2-regulated transcripts,...
Source: Physiological Genomics - August 6, 2009 Category: Genetics & Stem Cells Authors: Goetz, F. W., Rise, M. L., Rise, M., Goetz, G. W., Binkowski, F., Shepherd, B. S. Tags: Call For Papers: Comparative Genomics Source Type: journals
Protein families reflect the metabolic diversity of organisms and provide support for functional prediction
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Comparative genomics has shown that protein families vary significantly within and across organisms in both number and functional composition. In the present work, we tested how the diversity at the family level reflects biological differences among organisms and contributes to their unique characteristics. For this purpose, we collected sequence-similar proteins of three selected families from model bacteria: Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa. Protein relationships were identified using a phylogenomic approach to connect the functional diversity of enzymes to the metabolic capabilities of the...
Source: Physiological Genomics - August 6, 2009 Category: Genetics & Stem Cells Authors: Nahum, L. A., Goswami, S., Serres, M. H. Tags: Call For Papers: Comparative Genomics Source Type: journals
QTL for several metabolic traits map to loci controlling growth and body composition in an F2 intercross between high- and low-growth chicken lines
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Quantitative trait loci (QTL) for metabolic and body composition traits were mapped at 7 and 9 wk, respectively, in an F2 intercross between high-growth and low-growth chicken lines. These lines also diverged for abdominal fat percentage (AFP) and plasma insulin-like growth factor-I (IGF-I), insulin, and glucose levels. Genotypings were performed with 129 microsatellite markers covering 21 chromosomes. A total of 21 QTL with genomewide level of significance were detected by single-trait analyses for body weight (BW), breast muscle weight (BMW) and percentage (BMP), AF weight (AFW) and percentage (AFP), shank length (ShL) a...
Source: Physiological Genomics - August 6, 2009 Category: Genetics & Stem Cells Authors: Nadaf, J., Pitel, F., Gilbert, H., Duclos, M. J., Vignoles, F., Beaumont, C., Vignal, A., Porter, T. E., Cogburn, L. A., Aggrey, S. E., Simon, J., Le Bihan-Duval, E. Tags: Call For Papers: Comparative Genomics Source Type: journals
Gene expression profiles in peripheral blood mononuclear cells of chronic heart failure patients
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The present study was aimed at identifying chronic heart failure (CHF) biomarkers from peripheral blood mononuclear cells (PBMCs) in patients with ischemic (ICM) and nonischemic dilated (NIDCM) cardiomyopathy. PBMC gene expression profiling was performed by Affymetrix in two patient groups, 1) ICM (n = 12) and 2) NIDCM (n = 12) New York Heart Association (NYHA) III/IV CHF patients, vs. 3) age- and sex-matched control subjects (n = 12). Extracted RNAs were then pooled and hybridized to a total of 11 microarrays. Gene ontology (GO) analysis separated gene profiling into functional classes. Prediction analysis of microarrays ...
Source: Physiological Genomics - August 6, 2009 Category: Genetics & Stem Cells Authors: Cappuzzello, C., Napolitano, M., Arcelli, D., Melillo, G., Melchionna, R., Di Vito, L., Carlini, D., Silvestri, L., Brugaletta, S., Liuzzo, G., Crea, F., Capogrossi, M. C. Tags: Call For Papers: Comparative Genomics Source Type: journals
Characterization of Nob3, a major quantitative trait locus for obesity and hyperglycemia on mouse chromosome 1
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New Zealand obese (NZO) mice present a metabolic syndrome of obesity, insulin resistance, and diabetes. To identify chromosomal segments associated with these traits, we intercrossed NZO mice with the lean and diabetes-resistant C57BL/6J (B6) strain. Obesity and hyperglycemia in the (NZOxB6)F2 intercross population were predominantly due to a broad quantitative trait locus (QTL) on chromosome 1 (Nob3; logarithm of the odds score 16.1, 16.0, 4.0 for body weight, body fat, and blood glucose, respectively), producing a difference between genotypes of 12.7 or 5.2 g of body weight and 12.0 or 4.0 g of body fat in females or mal...
Source: Physiological Genomics - July 8, 2009 Category: Genetics & Stem Cells Authors: Vogel, H., Nestler, M., Ruschendorf, F., Block, M.-D., Tischer, S., Kluge, R., Schurmann, A., Joost, H.-G., Scherneck, S. Tags: Research Articles Source Type: journals
Individual molecular response to elevated intraocular pressure in perfused postmortem human eyes
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Elevated intraocular pressure (IOP) is the major risk factor for glaucoma. In the clinic, the response to elevated pressure and thus the risk for development of glaucoma differs among individuals. We took advantage of our ability to subject postmortem human eyes from the same individual to physiological and elevated pressure in a perfused outflow model and compared individual patterns of gene expression under pressure. The architecture of the trabecular meshwork, tissue responsible for the maintenance of IOP, was conserved. We performed two sets of experiments. The first set (n = 5, 10 eyes) used Affymetrix GeneChips, iden...
Source: Physiological Genomics - July 8, 2009 Category: Genetics & Stem Cells Authors: Comes, N., Borras, T. Tags: Research Articles Source Type: journals
Inflammation-dependent expression of SPARC during development of chronic pancreatitis in WBN/Kob rats and a microarray gene expression analysis
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The pathophysiology of human chronic pancreatitis is not well understood and difficult to follow on a molecular basis. Therefore, we used a rat model [Wistar-Bonn/Kobori (WBN/Kob)] that exhibits spontaneous chronic inflammation and fibrosis in the pancreas. Using microarrays we compared gene expression patterns in the pancreas during development of inflammation and fibrosis of WBN/Kob rats with age-matched healthy Wistar rats. The extracellular matrix protein SPARC (secreted protein, acidic, and rich in cysteines) and other transcripts of inflammatory genes were quantified by real-time PCR, and some were localized by immun...
Source: Physiological Genomics - July 8, 2009 Category: Genetics & Stem Cells Authors: Reding, T., Wagner, U., Silva, A. B., Sun, L-K., Bain, M., Kim, S.-Y., Bimmler, D., Graf, R. Tags: Research Articles Source Type: journals
Foxa2-dependent hepatic gene regulatory networks depend on physiological state
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Bile acids are powerful detergents produced by the liver to aid in the absorption of dietary lipids. We recently reported a novel role for Foxa2 in bile acid metabolism. The winged helix transcription factor Foxa2 is required to prevent intrahepatic cholestasis and liver injury in mice fed a cholic acid-enriched diet. Here, we use functional genomics to study how Foxa2 regulates its targets in a cholic acid-dependent manner. We found that multiple signaling pathways essential for the hepatic response to acute liver injury are impaired in livers of Foxa2-deficient mice, suggesting that the deletion of Foxa2 in the hepatocyt...
Source: Physiological Genomics - July 8, 2009 Category: Genetics & Stem Cells Authors: Bochkis, I. M., Schug, J., Rubins, N. E., Chopra, A. R., O'Malley, B. W., Kaestner, K. H. Tags: Research Articles Source Type: journals
Effects of nitroglycerin or pentaerithrityl tetranitrate treatment on the gene expression in rat hearts: evidence for cardiotoxic and cardioprotective effects
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In conclusion, our data suggest that NTG treatment results in the induction of cardiotoxic gene expression networks leading to an activation of mechanisms that result in pathological changes in cardiomyocytes. In contrast, PETN treatment seems to activate gene expression networks that result in cardioprotective effects. (Source: Physiological Genomics)
Source: Physiological Genomics - July 8, 2009 Category: Genetics & Stem Cells Authors: Pautz, A., Rauschkolb, P., Schmidt, N., Art, J., Oelze, M., Wenzel, P., Forstermann, U., Daiber, A., Kleinert, H. Tags: Research Articles Source Type: journals
Muscle expression of genes associated with inflammation, growth, and remodeling is strongly correlated in older adults with resistance training outcomes
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A group (n = 8) of healthy older (68 ± 6 yr) adults participated in a 36-session progressive resistance exercise training program targeting the thigh muscles to determine the relationship between muscle gene expression and gains in muscle size and strength. Biopsies were obtained from the vastus lateralis at baseline 72 h after an acute bout of exercise and 72 h after completion of the training program. Training increased thigh muscle size (7%) and strength for the three exercises performed: knee extension (30%) and curl (28%) and leg press (20%). We quantified 18 transcripts encoding factors that function in inflam...
Source: Physiological Genomics - July 8, 2009 Category: Genetics & Stem Cells Authors: Dennis, R. A., Zhu, H., Kortebein, P. M., Bush, H. M., Harvey, J. F., Sullivan, D. H., Peterson, C. A. Tags: Research Articles Source Type: journals
Reciprocal backcross mice confirm major loci linked to hyperoxic acute lung injury survival time
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Morbidity and mortality associated with acute lung injury (ALI) and acute respiratory distress syndrome remain substantial. Although many candidate genes have been tested, a clear understanding of the pathogenesis is lacking, as is our ability to predict individual outcome. Because ALI is a complex disease, single gene approaches cannot easily identify effectors that must be treated concurrently. We employed a strategy to help identify critical genes and gene combinations involved in ALI mortality. Using hyperoxia to induce ALI, a mouse model for genetic analyses of ALI survival time was identified: C57BL/6J (B) mice are s...
Source: Physiological Genomics - July 8, 2009 Category: Genetics & Stem Cells Authors: Prows, D. R., Winterberg, A. V., Gibbons, W. J., Burzynski, B. B., Liu, C., Nick, T. G. Tags: Research Articles Source Type: journals
Equine thrombospondin II and secreted protein acidic and cysteine-rich in a model of normal and pathological wound repair
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This study is the first to characterize equine cDNA for THBS2 and SPARC and to document mRNA expression over the different phases of repair. THBS2 and SPARC might modulate angiogenesis during wound healing in the horse, which could protect against the disproportionate fibroplasia commonly afflicting limb wounds and leading to the development of exuberant granulation tissue. (Source: Physiological Genomics)
Source: Physiological Genomics - July 8, 2009 Category: Genetics & Stem Cells Authors: Miragliotta, V., Raphael, K., Ipina, Z., Lussier, J. G., Theoret, C. L. Tags: Research Articles Source Type: journals
Expression profiling of skeletal muscle in young bulls treated with steroidal growth promoters
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Dexamethasone (Dex), alone or in association with estrogens, is often illegally administered per os at very low dosage as a growth promoter in beef cattle, with effects that are opposite to the muscle wasting and atrophy induced by repeated administration at therapeutic dosages. In vitro and in vivo studies have investigated the catabolic effects of Dex at therapeutic doses on skeletal muscle, demonstrating an increase in the expression of GDF8 (myostatin) gene, a well-known negative regulator of skeletal muscle mass, in a dose-dependent way. This suggested a direct role of myostatin in Dex-induced muscle wasting. In the p...
Source: Physiological Genomics - July 8, 2009 Category: Genetics & Stem Cells Authors: Carraro, L., Ferraresso, S., Cardazzo, B., Romualdi, C., Montesissa, C., Gottardo, F., Patarnello, T., Castagnaro, M., Bargelloni, L. Tags: Research Articles Source Type: journals
Transcriptomic and proteomic analysis of global ischemia and cardioprotection in the rabbit heart
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Cardioplegia is used to partially alleviate the effects of surgically induced global ischemia injury; however, the molecular mechanisms involved in this cardioprotection remain to be elucidated. To improve the understanding of the molecular processes modulating the effects of global ischemia and the cardioprotection afforded by cardioplegia, we constructed rabbit heart cDNA libraries and isolated, sequenced, and identified a compendium of nonredundant cDNAs for use in transcriptomic and proteomic analyses. New Zealand White rabbits were used to compare the effects of global ischemia and cardioplegia compared with control (...
Source: Physiological Genomics - July 8, 2009 Category: Genetics & Stem Cells Authors: McCully, J. D., Bhasin, M. K., Daly, C., Guerrero, M. C., Dillon, S., Liberman, T. A., Cowan, D. B., Mably, J. D., McGowan, F. X., Levitsky, S. Tags: Call For Papers: Comparative Genomics Source Type: journals
Analysis of a large cluster of SLC22 transporter genes, including novel USTs, reveals species-specific amplification of subsets of family members
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When the organic anion transporter Oat1 was first identified as NKT (Lopez-Nieto CE, You G, Bush KT, Barros EJ, Beier DR, Nigam SK. J Biol Chem 272: 6471–6478, 1997), it was argued that it, together with Oct1, may be part of a larger subfamily (now known as SLC22) involved in organic ion and xenobiotic transport. The least studied among SLC22 transporters are the so-called unknown substrate transporters (USTs). Here, five novel genes located in a cluster on mouse chromosome 19, immediately between Slc22a8 (Oat3)/Slc22a6 (Oat1) and Slc22a19 (Oat5), were identified as homologs of human USTs. These genes display prefere...
Source: Physiological Genomics - July 8, 2009 Category: Genetics & Stem Cells Authors: Wu, W., Baker, M. E., Eraly, S. A., Bush, K. T., Nigam, S. K. Tags: Call For Papers: Comparative Genomics Source Type: journals
MicroRNA: a new entrance to the broad paradigm of systems molecular medicine
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Systems molecular medicine is the science of combining systems biology with molecular analysis and intervention to address clinically relevant questions. MicroRNAs (miRNAs) appear particularly suitable to serve as hubs of regulatory networks underlying complex diseases. Clear experimental evidence for coordinated regulation of a large number of genes by miRNAs, however, is still rare. It leaves open several fundamental questions that are important for determining the value of miRNA in complex regulatory networks and in systems molecular medicine. Physiological genomics is a powerful approach for addressing these open quest...
Source: Physiological Genomics - July 8, 2009 Category: Genetics & Stem Cells Authors: Liang, M. Tags: Perspectives Source Type: journals
