MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Physiological Genomics' source. Sat, 20 Mar 2010 15:47:40 +0100 http://www.medworm.com/index.php?rid=3330354&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F41%2F1%2F102%3Frss%3D1 Heterogeneous stock (HS) animals provide the ability to map quantitative trait loci at high resolution [<5 Megabase (Mb)] in a relatively short time period. In the current study, we hypothesized that the HS rat colony would be useful for fine-mapping a region on rat chromosome 1 that has previously been implicated in glucose regulation. We administered a glucose tolerance test to 515 HS rats and genotyped these animals with 69 microsatellite markers, spaced an average distance of <1 Mb apart, on a 67 Mb region of rat chromosome 1. Using regression modeling of inferred haplotypes based on a hidden Markov model reconstruction and mixed model analysis in which we accounted for the complex family structure of the HS, we identified one sharp peak within this region. Using positional boots... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3330354 Wed, 03 Mar 2010 22:09:12 +0100 3330354 http://www.medworm.com/index.php?rid=3330353&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F41%2F1%2F91%3Frss%3D1 Chromogranin A (CHGA) plays a catalytic role in formation of catecholamine storage vesicles and also serves as precursor to the peptide fragment catestatin, a catecholamine secretory inhibitor whose expression is diminished in the hypertensive individuals. We previously reported the hypertensive, hyperadrenergic phenotype of Chga–/– knockout (KO) mice and rescue by the human ortholog. In the present study, we compare two humanized CHGA mouse models. Into the Chga null background, by bacterial artificial chromosome transgenesis human CHGA transgene has been introduced. Both lines have the complete ~12 kbp CHGA gene integrated stably in the genome but have substantial differences in CHGA expression, as well as consequent sympathochromaffin biochemistry and physiology. A mouse mod... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3330353 Wed, 03 Mar 2010 22:09:12 +0100 3330353 http://www.medworm.com/index.php?rid=3330352&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F41%2F1%2F82%3Frss%3D1 We compared a polygenic profile that combined 33 disease risk-related mutations and polymorphisms among nonathletic healthy control subjects and elite endurance athletes. The study sample comprised 100 healthy Spanish male nonathletic (sedentary) control subjects and 100 male elite endurance athletes. We analyzed 33 disease risk-related mutations and polymorphisms. We computed a health-related total genotype score (TGS, 0–100) from the accumulated combination of the 33 variants. We did not observe significant differences in genotype or allele distributions among groups, except for the rs4994 polymorphism (P < 0.001). The computed health-related TGS was similar among groups (23.8 ± 1.0 vs. 24.2 ± 0.8 in control subjects and athletes, respectively; P = 0.553). Similar ... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3330352 Wed, 03 Mar 2010 22:09:12 +0100 3330352 http://www.medworm.com/index.php?rid=3330351&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F41%2F1%2F78%3Frss%3D1 In conclusion, our data indicate that the NRF2 A/C and NRF2 C/T single nucleotide polymorphisms (SNPs) are associated, separately and in combination, with elite endurance athletes, which supports the notion that these specific gene variants might belong to a growing group of SNPs that are associated with endurance performance. (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3330351 Wed, 03 Mar 2010 22:09:12 +0100 3330351 http://www.medworm.com/index.php?rid=3330350&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F41%2F1%2F71%3Frss%3D1 Airway inflammation and pulmonary disease are heterogeneous phenotypes in cystic fibrosis (CF) patients, even among patients with the same cystic fibrosis transmembrane conductance regulator (CFTR) genotype. Endothelin, a proinflammatory peptide and smooth muscle agonist, is increased in CF airways, potentially contributing to the pulmonary phenotype. Four cohorts of CF patients were screened for variants in endothelin pathway genes to determine whether any of these variants associated with pulmonary function. An initial cohort of 808 CF patients homozygous for the common CF mutation, F508, showed significant association for polymorphisms in the endothelin receptor A gene, EDNRA (P = 0.04), but not in the related endothelin genes (EDN1, EDN2, EDN3, or EDNRB) or NOS1, NOS2A, or NOS3. Varian... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3330350 Wed, 03 Mar 2010 22:09:11 +0100 3330350 http://www.medworm.com/index.php?rid=3330349&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F41%2F1%2F63%3Frss%3D1 Chromosome 13 consomic and congenic rat strains were analyzed to investigate the pattern of genomic pathway utilization involved in protection against salt-sensitive hypertension and renal injury. Introgression of the entire Brown-Norway chromosome 13 (consomic SS-13BN) or nonoverlapping segments of this chromosome (congenic strains, 16 Mbp in D13Rat151–D13Rat197 or 14 Mbp in D13Rat111–D13Got22) into the genome of the Dahl salt-sensitive rat attenuated salt-induced hypertension and proteinuria. mRNA abundance profiles in the renal cortex and the renal medulla from rats receiving 0.4% or 8% NaCl diets revealed two important features of pathway recruitment in these rat strains. First, the two congenic strains shared alterations in several pathways compared with Dahl salt-sensitiv... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3330349 Wed, 03 Mar 2010 22:09:11 +0100 3330349 http://www.medworm.com/index.php?rid=3330348&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F41%2F1%2F53%3Frss%3D1 In conclusion we have characterized the temporal expression pattern of these genes and modulation of their transcript abundance by P4 (CTGF, LPL) and/or the conceptus (CTGF, SLC5A1) likely modifies the uterine microenvironment, enhancing histotroph composition and contributing to advanced conceptus elongation. (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3330348 Wed, 03 Mar 2010 22:09:11 +0100 3330348 http://www.medworm.com/index.php?rid=3330347&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F41%2F1%2F42%3Frss%3D1 Little is known about the role of the transcription factor peroxisome proliferator-activated receptor (PPAR) β/ in liver. Here we set out to better elucidate the function of PPARβ/ in liver by comparing the effect of PPAR and PPARβ/ deletion using whole genome transcriptional profiling and analysis of plasma and liver metabolites. In fed state, the number of genes altered by PPAR and PPARβ/ deletion was similar, whereas in fasted state the effect of PPAR deletion was much more pronounced, consistent with the pattern of gene expression of PPAR and PPARβ/. Minor overlap was found between PPAR- and PPARβ/-dependent gene regulation in liver. Pathways upregulated by PPARβ/ deletion were connected to innate immunity and inflammation. Pathways downregulated by P... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3330347 Wed, 03 Mar 2010 22:09:11 +0100 3330347 http://www.medworm.com/index.php?rid=3330346&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F41%2F1%2F33%3Frss%3D1 Mitochondria accumulate at sites of intense metabolic activity within cells, but the adaptive value of this placement is not clear. In Drosophila, sesB encodes the ubiquitous isoform of adenine nucleotide translocase (ANT, the mitochondrial inner membrane ATP/ADP exchanger); null alleles are lethal, whereas hypomorphic alleles display sensitivity to a range of stressors. In the adult renal tubule, which is densely packed with mitochondria and hence enriched for sesB, both hypomorphic alleles and RNA interference knockdowns cause the mitochondria to lose their highly polarized distribution in the tissue and to become rounded. Basal cytoplasmic and mitochondrial calcium levels are both increased, and neuropeptide calcium response compromised, with concomitant defects in fluid secretion. The ... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3330346 Wed, 03 Mar 2010 22:09:11 +0100 3330346 http://www.medworm.com/index.php?rid=3330345&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F41%2F1%2F21%3Frss%3D1 Regulation of milk synthesis and secretion is controlled mostly through local (intramammary) mechanisms. To gain insight into the molecular pathways comprising this response, an analysis of mammary gene expression was conducted in 12 lactating cows shifted from twice daily to once daily milking. Tissues were sampled by biopsy from adjacent mammary quarters of these animals during the two milking frequencies, allowing changes in gene expression to be assessed within each animal. Using bovine-specific, oligonucleotide arrays representing 21,495 unique transcripts, a range of differentially expressed genes were found as a result of less frequent milk removal, constituting transcripts and pathways related to apoptotic signaling (NF-B, JUN, ATF3, IGFBP5, TNFSF12A) mechanical stress and epitheli... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3330345 Wed, 03 Mar 2010 22:09:11 +0100 3330345 http://www.medworm.com/index.php?rid=3330344&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F41%2F1%2F9%3Frss%3D1 Rodents homozygous for autosomal leptin receptor gene mutations not only become obese, insulin resistant, and hyperleptinemic but also develop a dysregulated immune system. Using marker-assisted breeding to introgress the Koletsky rat leptin receptor mutant (lepr–/lepr–), we developed a novel congenic BBDR.lepr–/lepr– rat line to study the development of obesity and type 2 diabetes (T2D) in the BioBreeding (BB) diabetes-resistant (DR) rat. While heterozygous lepr (–/+) or homozygous (+/+) BBDR rats remained lean and metabolically normal, at 3 wk of age all BBDR.lepr–/lepr– rats were obese without hyperglycemia. Between 45 and 70 days of age, male but not female obese rats developed T2D. We had previously developed congenic BBDR.Gimap5–/Gimap5... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3330344 Wed, 03 Mar 2010 22:09:11 +0100 3330344 http://www.medworm.com/index.php?rid=3330343&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F41%2F1%2F1%3Frss%3D1 In this study, we sought to determine the similarity of the effects of tobacco smoke throughout the respiratory tract by determining patterns of smoking-related gene expression in paired nasal and bronchial epithelial brushings collected from 14 healthy nonsmokers and 13 healthy current smokers. Using whole genome expression arrays, we identified 119 genes whose expression was affected by smoking similarly in both bronchial and nasal epithelium, including genes related to detoxification, oxidative stress, and wound healing. While the vast majority of smoking-related gene expression changes occur in both bronchial and nasal epithelium, we also identified 27 genes whose expression was affected by smoking more dramatically in bronchial epithelium than nasal epithelium. Both common and site-sp... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3330343 Wed, 03 Mar 2010 22:09:11 +0100 3330343 http://www.medworm.com/index.php?rid=3242733&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Ffull%2F40%2F3%2F217%3Frss%3D1 (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3242733 Thu, 04 Feb 2010 21:04:46 +0100 3242733 http://www.medworm.com/index.php?rid=3242732&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Ffull%2F40%2F3%2F216%3Frss%3D1 (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3242732 Thu, 04 Feb 2010 21:04:46 +0100 3242732 http://www.medworm.com/index.php?rid=3242731&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F3%2F208%3Frss%3D1 In this study, we present the use of FPLC in conjunction with nano-HPLC-ESI-tandem mass spectrometry as a new integrated methodology suitable for the proteomic analysis of human lipoprotein fractions. Results from our analysis show that only 200 µl of human plasma suffices for the isolation of whole high density lipoprotein (HDL) and the identification of the majority of all known HDL-associated proteins using mass spectrometry of the resulting fractions. (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3242731 Thu, 04 Feb 2010 21:04:46 +0100 3242731 http://www.medworm.com/index.php?rid=3242730&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F3%2F195%3Frss%3D1 Chromogranin A (CHGA) has a crucial role in formation of regulated secretory granules in neuroendocrine tissues and is also a prohormone that is proteolytically processed into peptides with diverse and complex actions. CHGA and several of its peptide products, including catestatin and pancreastatin, are implicated in pathogenesis of essential hypertension, insulin resistance, and the metabolic syndrome. The Chga knockout mouse (Chga KO) displays severe hypertension coupled with reduction in size, number, and density of regulated secretory granules. We performed genome-wide transcriptome profiling in Chga KO adrenal gland and liver for insight into biochemical and physiological systems altered in this monogenic mouse model of hypertension. Adrenal gene expression pathway prediction of enhan... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3242730 Thu, 04 Feb 2010 21:04:46 +0100 3242730 http://www.medworm.com/index.php?rid=3242729&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F3%2F189%3Frss%3D1 In conclusion, these preliminary results suggest that the anti-inflammatory effects of fish consumption can be explained by a synergistic effect of the omega-3 FA with the protein components of fish on TNF expression and therefore contribute to the beneficial effects of fish consumption. Hence, follow-up studies should be performed to confirm the effects of a diet rich in FPH and omega-3 FA on serum proinflammatory cytokine concentrations. (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3242729 Thu, 04 Feb 2010 21:04:45 +0100 3242729 http://www.medworm.com/index.php?rid=3242728&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F3%2F184%3Frss%3D1 Buffering of blood pressure during change of posture such as standing is controlled largely by the baroreflex. In our population-based Victorian Family Heart Study (VFHS), we previously demonstrated that, on average, systolic blood pressure (SBP) changes very little on standing; however, interindividual variation is substantial and shows familial aggregation, with ~25% of the variance attributable to genetic factors. Our genomewide linkage analysis suggests a region on chromosome 12p that harbors two strong candidate genes, KCNJ8 and ABCC9, encoding the channel-forming inward rectifier subunit Kir6.1 and the ATP-sensitive binding cassette SUR2B, respectively. These are key components of smooth muscle ATP-sensitive potassium (KATP) channels, important regulators of arterial tone and blood f... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3242728 Thu, 04 Feb 2010 21:04:45 +0100 3242728 http://www.medworm.com/index.php?rid=3242727&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F3%2F167%3Frss%3D1 Vasopressin is a peptide hormone that regulates renal water excretion in part through its actions on the collecting duct. The regulation occurs in part via control of transcription of genes coding for the water channels aquaporin-2 (Aqp2) and aquaporin-3 (Aqp3). To identify transcription factors expressed in collecting duct cells, we have carried out LC-MS/MS-based proteomic profiling of nuclei isolated from native rat inner medullary collecting ducts (IMCDs). To maximize the number of proteins identified, we matched spectra to rat amino acid sequences using three different search algorithms (SEQUEST, InsPecT, and OMSSA). All searches were coupled to target-decoy methodology to limit false-discovery identifications to 2% of the total for single-peptide identifications. In addition, we deve... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3242727 Thu, 04 Feb 2010 21:04:45 +0100 3242727 http://www.medworm.com/index.php?rid=3242726&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F3%2F158%3Frss%3D1 We investigated the effects on urinary steroid and electrolyte excretion and renal gene expression of chronic infusions of ACTH in the mouse. ACTH caused a sustained increase in corticosteroid excretion; aldosterone excretion was only transiently elevated. There was an increase in the excretion of deoxycorticosterone, a weak mineralocorticoid, to levels of physiological significance. Nevertheless, we observed neither antinatriuresis nor kaliuresis in ACTH-treated mice, and plasma renin activity was not suppressed. We identified no changes in expression of mineralocorticoid target genes. Water turnover was increased in chronic ACTH-treated mice, as were hematocrit and hypertonicity: volume contraction is consistent with high levels of glucocorticoid. ACTH-treated mice exhibited other signs ... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3242726 Thu, 04 Feb 2010 21:04:45 +0100 3242726 http://www.medworm.com/index.php?rid=3242725&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F3%2F150%3Frss%3D1 Valve formation during embryonic heart development involves a complex interplay of regional specification, cell transformations, and remodeling events. While many studies have addressed the role of specific genes during this process, a global understanding of the genetic basis for the regional specification and development of the heart valves is incomplete. We have undertaken genome-wide transcriptional profiling of the developing heart valves in the mouse. Four Serial Analysis of Gene Expression libraries were generated and analyzed from the mouse atrio-ventricular canal (AVC) at embryonic days 9.5–12.5, covering the stages from initiation of endothelial to mesenchymal transition (EMT) through to the beginning of endocardial cushion remodeling. We identified 14 distinct temporal pat... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3242725 Thu, 04 Feb 2010 21:04:45 +0100 3242725 http://www.medworm.com/index.php?rid=3242724&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F3%2F141%3Frss%3D1 Across numerous model systems, aging skeletal muscle demonstrates an impaired regenerative response when exposed to the same stimulus as young muscle. To better understand the impact of aging in a human model, we compared changes to the skeletal muscle transcriptome induced by unaccustomed high-intensity resistance loading (RL) sufficient to cause moderate muscle damage in young (37 yr) vs. older (73 yr) adults. Serum creatine kinase was elevated 46% 24 h after RL in all subjects with no age differences, indicating similar degrees of myofiber membrane wounding by age. Despite this similarity, from genomic microarrays 318 unique transcripts were differentially expressed after RL in old vs. only 87 in young subjects. Follow-up pathways analysis and functional annotation revealed among old su... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3242724 Thu, 04 Feb 2010 21:04:45 +0100 3242724 http://www.medworm.com/index.php?rid=3242723&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F3%2F128%3Frss%3D1 In this study we develop methods of examining gene expression dynamics, how and when genes change expression, and demonstrate their application in a meta-analysis involving over 29,000 microarrays. By defining measures across many experimental conditions, we have a new way of characterizing dynamics, complementary to measures looking at changes in absolute variation or breadth of tissues showing expression. We show conservation in overall patterns of dynamism across three species (human, mouse, and rat) and show associations with known disease-related genes. We discuss the enriched functional properties of the sets of genes showing different patterns of dynamics and show that the differences in expression dynamics is associated with the variety of different transcription factor regulatory ... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3242723 Thu, 04 Feb 2010 21:04:45 +0100 3242723 http://www.medworm.com/index.php?rid=3242722&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F3%2F121%3Frss%3D1 Copy number variation (CNV) is increasingly recognized as a source of phenotypic variation among humans. We hypothesized that a CNV in the human arginine vasopressin receptor-2 gene (AVPR2) would be associated with serum sodium concentration based on the following lines of evidence: 1) the protein product of the AVPR2 gene is essential for renal water conservation; 2) mutations in the AVPR2 gene are associated with aberrant water balance in humans; 3) heritability of serum sodium concentration may be greater in females than in males; 4) the AVPR2 gene is X-linked; and 5) a common CNV spanning the AVPR2 gene was recently described in a non-Hispanic Caucasian population. We developed a highly reproducible assay for AVPR2 CNV. Among 279 subjects with measured serum sodium concentration in the... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3242722 Thu, 04 Feb 2010 21:04:45 +0100 3242722 http://www.medworm.com/index.php?rid=3155488&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F2%2F111%3Frss%3D1 Despite the health-related benefits of exercise, many people do not engage in enough activity to realize the rewards, and little is known regarding the genetic or environmental components that account for this individual variation. We created and phenotyped a large G4 advanced intercross line originating from reciprocal crosses between mice with genetic propensity for increased voluntary exercise (HR line) and the inbred strain C57BL/6J. G4 females (compared to males) ran significantly more when provided access to a running wheel and were smaller with a greater percentage of body fat pre- and postwheel access. Change in body composition resulting from a 6-day exposure to wheels varied between the sexes with females generally regulating energy balance more precisely in the presence of exerc... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3155488 Fri, 08 Jan 2010 18:48:57 +0100 3155488 http://www.medworm.com/index.php?rid=3155487&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F2%2F100%3Frss%3D1 Previous in vitro studies found that nuclear factor erythroid-derived 2-like 1 (NFE2L1) was involved in mediating ascorbic acid-induced osterix expression and osteoblast differentiation via binding to the antioxidant response element of the osterix promoter. To test the role of NFE2L1 in regulating bone formation in vivo, we disrupted NFE2L1 specifically in osteoblasts. Mice expressing Cre under the control of Col12 promoter were crossed with NFE2L1 loxP mice to generate Cre+ knockout (KO) and Cre– wild-type (WT) mice. Skeletal measurements by DEXA revealed 8–10% and 9–11% reduction in total body BMC and bone area in the KO mice from 3 to 8 wk of age. Peripheral quantitative computed tomography analyses found both periosteal and endosteal circumferences were reduced by 6%... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3155487 Fri, 08 Jan 2010 18:48:57 +0100 3155487 http://www.medworm.com/index.php?rid=3155486&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F2%2F94%3Frss%3D1 Mutations in the gene coding for ATP-binding cassette protein A3 (ABCA3) are recognized as a genetic cause of lung disease of varying severity. Characterization of a number of mutant ABCA3 proteins has demonstrated that the mutations generally affect intracellular localization or the ability of the protein to hydrolyze ATP. A novel heterozygous mutation that results in the substitution of cysteine for arginine at amino acid 295 in ABCA3 was identified in a premature infant with chronic respiratory insufficiency and abnormal lamellar bodies. Sequencing of DNA performed in study participants demonstrated that this was a mutation and not a common variant. Plasmid vectors containing ABCA3 with the identified novel mutation tagged with green fluorescent protein on the carboxy terminus were gene... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3155486 Fri, 08 Jan 2010 18:48:57 +0100 3155486 http://www.medworm.com/index.php?rid=3155485&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F2%2F83%3Frss%3D1 Intense selection for elite racing performance in the Thoroughbred horse (Equus caballus) has resulted in a number of adaptive physiological phenotypes relevant to exercise; however, the underlying molecular mechanisms responsible for these characteristics are not well understood. Adaptive changes in mRNA expression in equine skeletal muscle were investigated by real-time qRT-PCR for a panel of candidate exercise-response genes following a standardized incremental-step treadmill exercise test in eight untrained Thoroughbred horses. Biopsy samples were obtained from the gluteus medius before, immediately after, and 4 h after exercise. Significant (P < 0.05) differences in gene expression were detected for six genes (CKM, COX4I1, COX4I2, PDK4, PPARGC1A, and SLC2A4) 4 h after exercise. Inv... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3155485 Fri, 08 Jan 2010 18:48:57 +0100 3155485 http://www.medworm.com/index.php?rid=3132865&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F1%2F61%3Frss%3D1 Terminal differentiation of mammary tissue into a functional epithelium that synthesizes and secretes milk occurs during pregnancy. The molecular mechanisms underlying this complex process are poorly understood, especially in ruminants. To obtain an overview of the ruminant mammary gland's final differentiation process, we conducted time-course gene expression analysis of five physiological stages: four during pregnancy (P46, P70, P90, and P110) and one after 40 days of lactation (L40). An appropriate loop experimental design was used to follow gene expression profiles. Using three nulliparous (pregnancy) or primiparous (lactation) goats per stage, we performed a comparison starting from nine dye-swaps and using a 22K bovine oligoarray. Statistical analysis revealed that the expression of ... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3132865 Wed, 30 Dec 2009 22:22:18 +0100 3132865 http://www.medworm.com/index.php?rid=3132864&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F1%2F48%3Frss%3D1 In conclusion, we have identified an array of endothelial genes modulated by attenuated PPAR signaling that may play important roles in the development of PH. (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3132864 Wed, 30 Dec 2009 22:22:18 +0100 3132864 http://www.medworm.com/index.php?rid=3132863&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F1%2F34%3Frss%3D1 Higher fat and lower carbohydrate and amino acid oxidation are observed in women compared with men during endurance exercise. We hypothesized that the observed sex difference is due to estrogen and that menstrual cycle phase or supplementation of men with 17β-estradiol (E2) would coordinately influence the mRNA content of genes involved in lipid and/or carbohydrate metabolism in skeletal muscle. Twelve men and twelve women had muscle biopsies taken before and immediately after 90 min of cycling at 65% peak oxygen consumption (Vo2peak). Women were studied in the midfollicular (Fol) and midluteal (Lut) phases, and men were studied after 8 days of E2 or placebo supplementation. Targeted RT-PCR was used to compare mRNA content for genes involved in transcriptional regulation and lipid, ca... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3132863 Wed, 30 Dec 2009 22:22:18 +0100 3132863 http://www.medworm.com/index.php?rid=3132862&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F1%2F23%3Frss%3D1 We examined the physiological and gene expression endpoints that chronic waterborne Cu exposure (21 d) imposes on soft-water acclimated zebrafish at two environmentally relevant concentrations: 8 µg/l (moderate) and 15 µg/l (high). Using a 16,730 65-mer oligonucleotide customized zebrafish microarray chip related to metal metabolism and toxicity to assess the transcriptomic response, we found that 573 genes in the liver responded significantly to Cu exposure. These clustered into three distinct patterns of expression. There was distinct upregulation of a majority of these genes under moderate Cu exposure and a significant downregulation under high Cu exposure. Microarray results were validated by qPCR of eight genes; two genes, metallothionein 2 (mt2) and Na+-K+-ATPase 1a1 (atp... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3132862 Wed, 30 Dec 2009 22:22:18 +0100 3132862 http://www.medworm.com/index.php?rid=3132861&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F1%2F15%3Frss%3D1 The genetic factors determining the magnitude of the response to exercise training are poorly understood. The aim of this study was to identify quantitative trait loci (QTL) associated with adaptation to exercise training in a cross between FVB/NJ (FVB) and C57BL/6J (B6) mice. Mice completed an exercise performance test before and after a 4-wk treadmill running program, and changes in exercise capacity, expressed as work (kg·m), were calculated. Changes in work in F2 mice averaged 1.51 ± 0.08 kg·m (94.3 ± 7.3%), with a range of –1.67 to +4.55 kg·m. All F2 mice (n = 188) were genotyped at 20-cM intervals with 103 single nucleotide polymorphisms (SNPs), and genomewide linkage scans were performed for pretraining, posttraining, and change in work. Sign... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3132861 Wed, 30 Dec 2009 22:22:18 +0100 3132861 http://www.medworm.com/index.php?rid=3132860&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F1%2F8%3Frss%3D1 Mutations in the human dysferlin gene cause Limb Girdle Muscular Dystrophy 2B (LGMD2B). The Caenorhabditis elegans dysferlin homolog, fer-1, affects sperms development but is not known to be expressed in or have a functional roles outside of the male germline. Using several approaches, we show that fer-1 mRNA is present in C. elegans muscle cells but is absent from neurons. In mammals, loss of muscle-expressed dysferlin causes transcriptional deregulation of muscle expressed genes. To determine if similar alterations in gene expression are initiated in C. elegans due to loss of muscle-expressed fer-1, we performed whole genome Affymetrix microarray analysis of two loss-of-function fer-1 mutants. Both mutants gave rise to highly similar changes in gene expression and altered the expression ... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3132860 Wed, 30 Dec 2009 22:22:18 +0100 3132860 http://www.medworm.com/index.php?rid=3132859&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F40%2F1%2F1%3Frss%3D1 Small maladaptations in cellular response to environmental stressors may underlie diseases like asthma. However, genomewide transcriptional profile comparisons between case and controls only highlight the quantitatively largest changes. Critical cellular homeostatic pathways may be upregulated modestly during normal adaptation to stress but insufficiently during disease. To discover such pathways in asthma, we utilized public information on differential response of primary bronchial epithelial cells from asthmatic or normal subjects to stressors like ozone and viral infections. Genes that were upregulated by stressor conditions in normal cells but were relatively downregulated in cells from asthmatic subjects were selected for further analysis. Either a stringent selection based on quantit... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=3132859 Wed, 30 Dec 2009 22:22:18 +0100 3132859 http://www.medworm.com/index.php?rid=2969547&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F3%2F227%3Frss%3D1 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 modified by RFR and CR, each regimen differentially changed the expression of distinct genes in each region. The most profound change was observed in the amygdalas of CR mice... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2969547 Fri, 06 Nov 2009 19:16:58 +0100 2969547 http://www.medworm.com/index.php?rid=2969546&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F3%2F219%3Frss%3D1 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 soleus muscle subjected to hindlimb suspension for 28 days provided evidence consistent with MyomiR network repression of β-myosin heavy chain gene (β-MHC) express... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2969546 Fri, 06 Nov 2009 19:16:58 +0100 2969546 http://www.medworm.com/index.php?rid=2969545&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F3%2F210%3Frss%3D1 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, increased compared with control, indicating that miR-290 is causally involved in senescence. Interestingly, nocodazole (NCZ), which induces G2/M block, increased the percent... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2969545 Fri, 06 Nov 2009 19:16:58 +0100 2969545 http://www.medworm.com/index.php?rid=2969544&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F3%2F202%3Frss%3D1 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 termination. Among the 31 genes we examined, 4 were expressed more highly in early diapause than in nondiapause, while 14 genes were downregulated in early diapause. In the tr... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2969544 Fri, 06 Nov 2009 19:16:58 +0100 2969544 http://www.medworm.com/index.php?rid=2969543&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F3%2F195%3Frss%3D1 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 cause a substitution (p.Arg329Pro) or a deletion (p.Ser310del) of highly conserved amino acid residues in the POU homeodomain or a truncation that eliminates both DNA-bin... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2969543 Fri, 06 Nov 2009 19:16:57 +0100 2969543 http://www.medworm.com/index.php?rid=2969542&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F3%2F183%3Frss%3D1 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 tert-butylhydroquinone. The present evidence of a conserved GSH homeostasis pathway in C. intestinalis together with its phylogenetic position as a basal chordate and lifes... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2969542 Fri, 06 Nov 2009 19:16:57 +0100 2969542 http://www.medworm.com/index.php?rid=2969541&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F3%2F172%3Frss%3D1 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 have similar transcriptional profiles on a low-fat diet, but strains may show considerable variability in response to high-fat diet. Functional profiling indicated that hi... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2969541 Fri, 06 Nov 2009 19:16:57 +0100 2969541 http://www.medworm.com/index.php?rid=2969540&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Ffull%2F39%2F3%2F169%3Frss%3D1 (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2969540 Fri, 06 Nov 2009 19:16:57 +0100 2969540 http://www.medworm.com/index.php?rid=2969539&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F3%2F160%3Frss%3D1 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 ectopic expression of the proosteogenic growth factor pleiotrophin (Ptn) and overexpression of delta-like 1 homolog (Dlk1), a negative regulator of Notch1, in the distal (... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2969539 Fri, 06 Nov 2009 19:16:57 +0100 2969539 http://www.medworm.com/index.php?rid=2969538&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F3%2F141%3Frss%3D1 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, extracellular matrix, energy metabolism, sarcomeric and LIM protein mRNA levels were downregulated, while ubiquitin proteasome system, cathepsins, oxidative stress responsive ge... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2969538 Fri, 06 Nov 2009 19:16:57 +0100 2969538 http://www.medworm.com/index.php?rid=2969537&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F3%2F131%3Frss%3D1 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) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2969537 Fri, 06 Nov 2009 19:16:57 +0100 2969537 http://www.medworm.com/index.php?rid=2870955&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F2%2F120%3Frss%3D1 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 experiments confirmed the transcriptome analysis predictions. For instance, a significant increase of TUNEL-positive follicles was found in Ddr2slie/slie mutants vs. wil... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2870955 Wed, 07 Oct 2009 22:11:52 +0100 2870955 http://www.medworm.com/index.php?rid=2870954&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F2%2F109%3Frss%3D1 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, and trans-esterification to produce complex lipids. The metabolic changes induced during differentiation of the 3T3-L1 cell line were then compared with the metabolic diffe... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2870954 Wed, 07 Oct 2009 22:11:52 +0100 2870954 http://www.medworm.com/index.php?rid=2870953&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F2%2F100%3Frss%3D1 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 genes related to cell adhesion, extracellular matrix, pattern specification and organogenesis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed high... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2870953 Wed, 07 Oct 2009 22:11:52 +0100 2870953 http://www.medworm.com/index.php?rid=2870952&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F2%2F85%3Frss%3D1 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 Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to identify functional groups of genes and biological processes in the endometrium that ar... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2870952 Wed, 07 Oct 2009 22:11:52 +0100 2870952 http://www.medworm.com/index.php?rid=2870951&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Ffull%2F39%2F2%2F83%3Frss%3D1 (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2870951 Wed, 07 Oct 2009 22:11:52 +0100 2870951 http://www.medworm.com/index.php?rid=2781024&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F1%2F72%3Frss%3D1 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 which redifferentiation was attempted. All three expansion protocols induced dramatic changes in the expression profiles of pancreatic islets; many of these changes are share... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2781024 Tue, 08 Sep 2009 23:00:00 +0100 2781024 http://www.medworm.com/index.php?rid=2781023&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F1%2F61%3Frss%3D1 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 decrease in genes involved in cellular respiration and energy metabolism and increases in inflammatory cell adhesion molecules and extracellular matrix proteins. Signal pa... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2781023 Tue, 08 Sep 2009 23:00:00 +0100 2781023 http://www.medworm.com/index.php?rid=2781022&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F1%2F56%3Frss%3D1 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 variants in the kininogen gene (KNG) that influence interindividual variation in aldosterone response. The significant association was replicated in three of four studied... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2781022 Tue, 08 Sep 2009 23:00:00 +0100 2781022 http://www.medworm.com/index.php?rid=2781021&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F1%2F47%3Frss%3D1 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 was substituted into an otherwise complete C57BL/6J (B6) genome. The B6 and A/J parental strains exhibited pronounced differences in daily physical activity, sleep-wake st... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2781021 Tue, 08 Sep 2009 23:00:00 +0100 2781021 http://www.medworm.com/index.php?rid=2781020&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F1%2F38%3Frss%3D1 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 region involved in the late progression of the disorder (chromosome 4). A single region was identified for the onset of the renal phenotype proteinuria (chromosome 5). This r... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2781020 Tue, 08 Sep 2009 23:00:00 +0100 2781020 http://www.medworm.com/index.php?rid=2781019&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F1%2F28%3Frss%3D1 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 peripartum period and early lactation and dairy cows are therefore more vulnerable to bacterial infections causing mastitis and or endometritis at this time. A bovine Affy... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2781019 Tue, 08 Sep 2009 23:00:00 +0100 2781019 http://www.medworm.com/index.php?rid=2781018&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F1%2F14%3Frss%3D1 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 higher on the immune response function in C but more prominent on the regulation of metabolism function in IC. The C vs. IC direct comparison revealed 1,177 and 453 DEG in cy... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2781018 Tue, 08 Sep 2009 23:00:00 +0100 2781018 http://www.medworm.com/index.php?rid=2781017&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F39%2F1%2F1%3Frss%3D1 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-hydroxybutyrate concentrations were raised. White blood cell count and lymphocyte number were reduced in SNEB cows. Array analysis of endometrial samples identified 274 d... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2781017 Tue, 08 Sep 2009 23:00:00 +0100 2781017 http://www.medworm.com/index.php?rid=2680990&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F3%2F386%3Frss%3D1 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 interactomes increase. Physiological responses to copper include transition metal ion binding and responses to stress/stimulus, whereas toxicological responses include apoptosis... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2680990 Thu, 06 Aug 2009 23:00:00 +0100 2680990 http://www.medworm.com/index.php?rid=2680989&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F3%2F372%3Frss%3D1 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 characteristically possessed increased focal adhesion numbers and displayed more rapid attachment compared with wild-type MEFs. Differential microarray analyses revealed alterations ... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2680989 Thu, 06 Aug 2009 23:00:00 +0100 2680989 http://www.medworm.com/index.php?rid=2680988&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F3%2F362%3Frss%3D1 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 genes, analyzed them for the enrichment of known promoter elements and pathways, and constructed a network module based on weighted gene coexpression network analysis (WGCNA... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2680988 Thu, 06 Aug 2009 23:00:00 +0100 2680988 http://www.medworm.com/index.php?rid=2680987&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F3%2F351%3Frss%3D1 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 mature prespawning female goldfish were exposed to fadrozole (50 µg/l) in March and April when goldfish have the highest AroB activity and maximal gonadal size. Fadr... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2680987 Thu, 06 Aug 2009 23:00:00 +0100 2680987 http://www.medworm.com/index.php?rid=2680986&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F3%2F342%3Frss%3D1 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 induction of Cre activity in mice with normal myostatin genes), at which time the expression of several hundred genes differed in knockout and control mice at nominal P ... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2680986 Thu, 06 Aug 2009 23:00:00 +0100 2680986 http://www.medworm.com/index.php?rid=2680985&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F3%2F328%3Frss%3D1 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 kinase (PERK). So far, the main known distinction among these four kinases is their activation in response to different acute stressors. In the present study, we used the ... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2680985 Thu, 06 Aug 2009 23:00:00 +0100 2680985 http://www.medworm.com/index.php?rid=2680984&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F3%2F319%3Frss%3D1 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 without affecting vascular development. Gene expression in whole embryo RNA from tnnt2 or control morphants at 36, 48, and 60 h postfertilization (hpf) was assessed using... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2680984 Thu, 06 Aug 2009 23:00:00 +0100 2680984 http://www.medworm.com/index.php?rid=2680983&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F3%2F303%3Frss%3D1 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 progression, the complement and coagulation cascades, and chemokine signaling. Our results demonstrated that resiquimod treatment resulted in the normalization of the expression o... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2680983 Thu, 06 Aug 2009 23:00:00 +0100 2680983 http://www.medworm.com/index.php?rid=2680982&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F3%2F291%3Frss%3D1 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 were obtained using a customized microarray containing 6,681 muscles-relevant genes. A two-class statistical analysis was applied on 2,103 genes with consolidated expressio... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2680982 Thu, 06 Aug 2009 23:00:00 +0100 2680982 http://www.medworm.com/index.php?rid=2680981&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F3%2F281%3Frss%3D1 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 SLC26A4 mutations were found in only 2 of 116 deaf Chinese patients without EVA. The spectrum of SLC26A4 mutations differed among Chinese and U.S. subjects and included 10 pr... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2680981 Thu, 06 Aug 2009 23:00:00 +0100 2680981 http://www.medworm.com/index.php?rid=2680980&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F3%2F261%3Frss%3D1 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, EST frequencies between libraries were calculated within contiguous sequences that were assembled from the combined ESTs of both libraries. Frequencies were also determi... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2680980 Thu, 06 Aug 2009 23:00:00 +0100 2680980 http://www.medworm.com/index.php?rid=2680979&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F3%2F250%3Frss%3D1 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 these organisms. All protein families studied have distinct functional compositions across the selected bacteria as supported by our Bayesian analysis. Some conserved functi... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2680979 Thu, 06 Aug 2009 23:00:00 +0100 2680979 http://www.medworm.com/index.php?rid=2680978&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F3%2F241%3Frss%3D1 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) and diameter (ShD), fasting plasma glucose level (Gluc), and body temperature (Tb). Other suggestive QTL were identified for these parameters and for plasma IGF-I and none... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2680978 Thu, 06 Aug 2009 23:00:00 +0100 2680978 http://www.medworm.com/index.php?rid=2680977&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F3%2F233%3Frss%3D1 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 (PAM) and significance analysis of microarrays (SAM) were utilized in order to identify a molecular signature. Candidate markers were validated by quantitative real-time ... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2680977 Thu, 06 Aug 2009 23:00:00 +0100 2680977 http://www.medworm.com/index.php?rid=2587202&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F2%2F226%3Frss%3D1 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 males, respectively. In addition, significant QTL on chromosomes 3 and 13 and suggestive QTL on chromosomes 4, 6, 9, 12, 14, and 19 contributed to the obese phenotype. Dista... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2587202 Wed, 08 Jul 2009 23:00:00 +0100 2587202 http://www.medworm.com/index.php?rid=2587201&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F2%2F205%3Frss%3D1 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, identified the 20 most pressure-altered genes in each individual, and compared their pressure response in the other four. The second set (n = 5, 10 eyes) selected 21 relevant... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2587201 Wed, 08 Jul 2009 23:00:00 +0100 2587201 http://www.medworm.com/index.php?rid=2587200&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F2%2F196%3Frss%3D1 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 immunohistochemistry. When pancreatic inflammation becomes obvious at the age of 16 wk, several hundred genes are increased between 3- and 50-fold in WBN/Kob rats compared wit... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2587200 Wed, 08 Jul 2009 23:00:00 +0100 2587200 http://www.medworm.com/index.php?rid=2587199&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F2%2F186%3Frss%3D1 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 hepatocyte affects the liver on a large scale. We also discovered distinct feed-forward regulatory loops controlling Foxa2-dependent targets in a cholic acid-dependent or -indepen... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2587199 Wed, 08 Jul 2009 23:00:00 +0100 2587199 http://www.medworm.com/index.php?rid=2587198&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F2%2F176%3Frss%3D1 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) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2587198 Wed, 08 Jul 2009 23:00:00 +0100 2587198 http://www.medworm.com/index.php?rid=2587197&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F2%2F169%3Frss%3D1 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 inflammation, growth, and muscle remodeling that were demonstrated previously to be regulated by aging and acute exercise. The gain in extension strength and muscle size showed... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2587197 Wed, 08 Jul 2009 23:00:00 +0100 2587197 http://www.medworm.com/index.php?rid=2587196&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F2%2F158%3Frss%3D1 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 sensitive (i.e., die early), whereas 129X1/SvJ (S) mice are significantly more resistant, but with low penetrance. Segregation analysis of reciprocal F2 mice generated fro... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2587196 Wed, 08 Jul 2009 23:00:00 +0100 2587196 http://www.medworm.com/index.php?rid=2587195&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F2%2F149%3Frss%3D1 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) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2587195 Wed, 08 Jul 2009 23:00:00 +0100 2587195 http://www.medworm.com/index.php?rid=2587194&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F2%2F138%3Frss%3D1 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 present study, an oligonucleotide microarray platform was used to compare expression profiles of beef cattle muscle in animals treated with either Dex or Dex plus 17-&beta... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2587194 Wed, 08 Jul 2009 23:00:00 +0100 2587194 http://www.medworm.com/index.php?rid=2587193&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F2%2F125%3Frss%3D1 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 (nonischemic) hearts. The effects of RNA and protein synthesis on the cardioprotection afforded by cardioplegia were investigated separately by preperfusion with either -a... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2587193 Wed, 08 Jul 2009 23:00:00 +0100 2587193 http://www.medworm.com/index.php?rid=2587192&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F2%2F116%3Frss%3D1 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 preferential expression in liver and kidney, and one gene, AB056422, has several splicing variants with differential tissue expression and embryonic expression. Along with Slc22... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2587192 Wed, 08 Jul 2009 23:00:00 +0100 2587192 http://www.medworm.com/index.php?rid=2587191&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F2%2F113%3Frss%3D1 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 questions. (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2587191 Wed, 08 Jul 2009 23:00:00 +0100 2587191 http://www.medworm.com/index.php?rid=2500626&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F1%2F98%3Frss%3D1 Transcriptional profiling coupled with blood metabolite analyses were used to identify porcine genes and pathways that respond to a fasting treatment or to a D298N missense mutation in the melanocortin-4 receptor (MC4R) gene. Gilts (12 homozygous for D298 and 12 homozygous for N298) were either fed ad libitum or fasted for 3 days. Fasting decreased body weight, backfat, and serum urea concentration and increased serum nonesterified fatty acid. In response to fasting, 7,029 genes in fat and 1,831 genes in liver were differentially expressed (DE). MC4R genotype did not significantly affect gene expression, body weight, backfat depth, or any measured serum metabolite concentration. Pathway analyses of fasting-induced DE genes indicated that lipid and steroid synthesis was downregulated in bot... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2500626 Tue, 09 Jun 2009 23:00:00 +0100 2500626 http://www.medworm.com/index.php?rid=2500625&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F1%2F89%3Frss%3D1 Congenic DRF.f/f rats are protected from type 1 diabetes (T1D) by 34 Mb of F344 DNA introgressed proximal to the gimap5 lymphopenia gene. To dissect the genetic factor(s) that confer protection from T1D in the DRF.f/f rat line, DRF.f/f rats were crossed to inbred BBDR or DR.lyp/lyp rats to generate congenic sublines that were genotyped and monitored for T1D, and positional candidate genes were sequenced. All (100%) DR.lyp/lyp rats developed T1D by 83 days of age. Reduction of the DRF.f/f F344 DNA fragment by 26 Mb (42.52–68.51 Mb) retained complete T1D protection. Further dissection revealed that a 2 Mb interval of F344 DNA (67.41–70.17 Mb) (region 1) resulted in 47% protection and significantly delayed onset (P < 0.001 compared with DR.lyp/lyp). Retaining <1 Mb of F344 D... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2500625 Tue, 09 Jun 2009 23:00:00 +0100 2500625 http://www.medworm.com/index.php?rid=2500624&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F1%2F80%3Frss%3D1 Conclusion: Fatty acid-enriched diets significantly upregulated proliferation above normal physiological levels during puberty. Higher cellular proliferation during puberty caused by enriched fatty acid diets poses a potential increase risk of mammary cancer in later life. The human homologs of 27 of 62 cell cycle rat genes are included in a human breast cancer cluster of 45 cell cycle genes, further emphasizing the importance of our findings in the rat model. (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2500624 Tue, 09 Jun 2009 23:00:00 +0100 2500624 http://www.medworm.com/index.php?rid=2500623&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F1%2F73%3Frss%3D1 Phenotypic variation between individuals, such as different mRNA expression levels, is influenced by genetic and nongenetic factors. Although several studies have addressed the interplay between genotypes and expression profiles in various model organisms in the recent years, the detailed and relative contributions of genetic and nongenetic factors in regulating plasticity of gene expression in barrier organs (e.g., skin, gut), which are exposed to continuous environmental challenge, are still poorly understood. Here we systematically monitored the level of genetic control over genomewide mRNA expression profiles in the healthy intestinal mucosa of 10 monozygotic and 10 dizygotic human twin pairs with microarray analyses. Our results, which are supported by real-time PCR and analysis of mo... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2500623 Tue, 09 Jun 2009 23:00:00 +0100 2500623 http://www.medworm.com/index.php?rid=2500622&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F1%2F63%3Frss%3D1 Obesity is a leading cause of diabetes mellitus and hypertension. Molecular signals produced by adipose tissue may contribute to the pathogenesis of these two disorders. We showed previously that a specific segment of rat chromosome 20 (RNO20) contains a gene(s) regulating the degree of obesity, glucose intolerance, and hypertension in response to a chronic high-fat diet (HFD). Here we examined microarray gene expression profiles and cellular morphology of adipose tissues and whole body energy expenditure in this model. Adult male spontaneously hypertensive rats (SHR) and a congenic strain (SHR.1N) that differs from SHR by the above-mentioned segment of RNO20 were fed for 12 wk with HFD or a normal diet. At the end of this period, whole body energy expenditure was measured with indirect ca... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2500622 Tue, 09 Jun 2009 23:00:00 +0100 2500622 http://www.medworm.com/index.php?rid=2500621&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F1%2F54%3Frss%3D1 Uncoupling protein 3 (Ucp3) is a transport protein of the inner mitochondrial membrane and presumably is implicated in the maintenance or tolerance of high lipid oxidation rates. Ucp3 is predominantly expressed in skeletal muscle and brown adipose tissue and is regulated by a transcription factor complex involving peroxisome proliferator-activated receptor-, MyoD, and COUP transcription factor II. By analysis of a mutant Djungarian hamster model lacking Ucp3 transcription specifically in brown adipose tissue, we identified a putative transcription factor-binding site that confers tissue specificity. A naturally occurring intronic point mutation disrupting this site leads to brown adipose tissue-specific loss of Ucp3 expression and an altered body weight trajectory. Our findings provide ins... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2500621 Tue, 09 Jun 2009 23:00:00 +0100 2500621 http://www.medworm.com/index.php?rid=2500620&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F1%2F42%3Frss%3D1 Activation of NF-B is essential for protease-activated receptor-1 (PAR-1)-mediated ICAM-1 expression in endothelial cells. Here we show that PAR-1 activation induces binding of both p65/RelA and NFATc1 to the NF-B binding site localized in intron-1 of the ICAM-1 gene to initiate transcription in endothelial cells. We discovered the presence of two NF-B binding sites in intron-1 (+70, NF-B site 1; +611, NF-B site 2) of the human ICAM-1 gene. Chromatin immunoprecipitation results showed that thrombin induced binding of p65/RelA and of NFATc1 specifically to intronic NF-B site 1 of the ICAM-1 gene. Electrophoretic mobility shift and supershift assays confirmed the binding of p65/RelA and NFATc1 to the intronic NF-B site 1 in thrombin-stimulated cells. Thrombin increased the expression of ICAM... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2500620 Tue, 09 Jun 2009 23:00:00 +0100 2500620 http://www.medworm.com/index.php?rid=2500619&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F1%2F29%3Frss%3D1 In conclusion, dynamic intercompartmental transport processes give rise to our surprising prediction that VEGF trapping alone does not account for sVEGFR1's antiangiogenic potential. sVEGFR1's interactions with cell surface receptors such as NRP1 are also expected to affect its molecular interplay with VEGF. (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2500619 Tue, 09 Jun 2009 23:00:00 +0100 2500619 http://www.medworm.com/index.php?rid=2500618&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F1%2F16%3Frss%3D1 Krüppel-related zinc finger proteins (KRAB-zfps) comprise the largest mammalian transcription factor family, but their specific functions are largely unknown. Two KRAB-zfps, regulator of sex-limitation (Rsl) 1 and Rsl2, repress expression of the mouse sex-limited protein (Slp) gene, the hallmark of Rsl activity, as well as some other male-predominant liver genes. This phenotype suggests Rsl modifies sex-specific transcription. The scope of Rsl control was determined by expression profiling of liver RNA from wild-type (wt), rsl, and transgenic mice with hepatic overexpression of Rsl1 or Rsl2. About 7.5% of the liver transcriptome was Rsl-responsive. More genes in males than females were affected by the loss of Rsl (e.g., in rsl mice), whereas Rsl overexpression altered more transcripts... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2500618 Tue, 09 Jun 2009 23:00:00 +0100 2500618 http://www.medworm.com/index.php?rid=2500617&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F1%2F7%3Frss%3D1 Cardiomyocytes derived from pluripotent embryonic stem cells (ESC) have the advantage of providing a source for standardized cell cultures. However, little is known on the regulation of the genome during differentiation of ESC to cardiomyocytes. Here, we characterize the transcriptome of the mouse ESC line CM7/1 during differentiation into beating cardiomyocytes and compare the gene expression profiles with those from primary adult murine cardiomyocytes and left ventricular myocardium. We observe that the cardiac gene expression pattern of fully differentiated CM7/1-ESC is highly similar to adult primary cardiomyocytes and murine myocardium, respectively. This finding is underlined by demonstrating pharmacological effects of catecholamines and endothelin-1 on ESC-derived cardiomyocytes. Fu... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2500617 Tue, 09 Jun 2009 23:00:00 +0100 2500617 http://www.medworm.com/index.php?rid=2500616&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F38%2F1%2F1%3Frss%3D1 In the postgenomic era, we need an algorithm to readily translate genes into physiologic principles. The failure to advance biomedicine is due to the false hope raised in the wake of the Human Genome Project (HGP) by the promise of systems biology as a ready means of reconstructing physiology from genes. like the atom in physics, the cell, not the gene, is the smallest completely functional unit of biology. Trying to reassemble gene regulatory networks without accounting for this fundamental feature of evolution will result in a genomic atlas, but not an algorithm for functional genomics. For example, the evolution of the lung can be "deconvoluted" by applying cell-cell communication mechanisms to all aspects of lung biology development, homeostasis, and regeneration/repair. Gene regulator... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2500616 Tue, 09 Jun 2009 23:00:00 +0100 2500616 http://www.medworm.com/index.php?rid=2411712&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Ffull%2F37%2F3%2F303%3Frss%3D1 (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2411712 Wed, 13 May 2009 04:00:00 +0100 2411712 http://www.medworm.com/index.php?rid=2411711&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F3%2F294%3Frss%3D1 HG.CAST-(D9Mit249-D9Mit133) (HG9) congenic mice are homozygous for CAST/EiJ chromosome (Chr) 9 alleles from ~9 to 84 Mbp on a C57BL6/J-hg/hg (HG) background. This region contains the carcass fat in high growth mice (Carfhg2) quantitative trait locus (QTL), and while its obesity-promoting effects have been confirmed in HG9 mice, its underlying genetic basis remains elusive. To refine the location of Carfhg2, we preformed a linkage analysis in two congenic F2 intercrosses and progeny-tested a recombinant F2 male. These analyses narrowed Carfhg2 to between 33.0 and 40.8 Mbp on Chr 9. To identify candidate genes we measured the expression of 44 transcripts surrounding the Carfhg2 peak in adipose, brain, liver, and muscle tissues from F2 mice using Biomark 48.48 Dynamic Arrays. In total, 68% (3... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2411711 Wed, 13 May 2009 04:00:00 +0100 2411711 http://www.medworm.com/index.php?rid=2411710&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F3%2F279%3Frss%3D1 Toxic shock syndrome (TSS) is an acute, serious systemic illness caused by bacterial superantigens. Nonavailability of a suitable animal model until recently has hampered an in-depth understanding of the pathogenesis of TSS. In the current study, we characterized the early molecular events underlying TSS using our HLA-DR3 transgenic mouse model. Gene expression profiling using DNA microarrays identified a rapid and significant upregulation of several pro- as well as anti-inflammatory mediators, many of which have never been previously described in TSS. In vivo administration of staphylococcal enterotoxin B (SEB) led to an increase in the expression of Th0- (IL-2, 240-fold); Th1- (IFN-, 360-fold; IL-12, 8-fold); Th2- (IL-4, 53-fold; IL-5, 4-fold) as well as Th17-type cytokines (IL-21, 19-fo... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2411710 Wed, 13 May 2009 04:00:00 +0100 2411710 http://www.medworm.com/index.php?rid=2411709&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F3%2F268%3Frss%3D1 MicroRNAs (miRNAs) are small endogenous RNAs and are widely regarded as one of the most important regulators of gene expression in both plants and animals. To define the roles of miRNAs in fetal lung development, we profiled the miRNA expression pattern during lung development with a miRNA microarray. We identified 21 miRNAs that showed significant changes in expression during lung development. These miRNAs were grouped into four distinct clusters based on their expression pattern. Cluster 1 contained miRNAs whose expression increased as development progressed, while clusters 2 and 3 showed the opposite trend of expression. miRNAs in cluster 4 including miRNA-127 (miR-127) had the highest expression at the late stage of fetal lung development. Quantitative real-time PCR validated the micro... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2411709 Wed, 13 May 2009 04:00:00 +0100 2411709 http://www.medworm.com/index.php?rid=2411708&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F3%2F260%3Frss%3D1 In this study, SOD3 transcript and protein localization were examined in mouse strains with differing ventilation efficiency [C3H/HeJ (high), JF1/Msf (low)] during postnatal lung development. Compared with C3H/HeJ mice, JF1/Msf mice had Sod3 promoter single nucleotide polymorphisms (SNPs) that could affect transcription factor binding sites and a decline in total lung SOD3 mRNA during postnatal development. In adult JF1/Msf mice, total lung SOD3 activity as well as SOD3 transcript and protein in airway epithelial and alveolar type II cells and the associated matrix decreased. In children (n = 1,555; age 9–11 yr), two common SOD3 SNPs, one located in the promoter region [C/T affecting a predicted aryl hydrocarbon receptor-xenobiotic response element (AhR-XRE) binding motif] and the ot... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2411708 Wed, 13 May 2009 04:00:00 +0100 2411708 http://www.medworm.com/index.php?rid=2411707&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F3%2F249%3Frss%3D1 The aim of present study was to describe changes in gene expression in the temporal lobe of mice induced by deletion of the Wfs1 gene. Temporal lobes samples were analyzed using Affymetrix Mouse Genome 420 2 GeneChips and expression profiles were functionally annotated with GSEA and Ingenuity Pathway Analysis. We found that Wfs1 mutant mice are significantly smaller (20.9 ± 1.6 g) than their wild-type counterparts (31.0 ± 0.6 g, P < 0.0001). This difference existed in 129S6 and C57B6 backgrounds. Interestingly, microarray analysis identified upregulation of growth hormone (GH) transcripts and functional analysis revealed activation of GH pathways. In line with microarray data, the level of IGF-1 in the plasma of Wfs1 mutant mice was significantly increased (P < 0.05). T... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2411707 Wed, 13 May 2009 04:00:00 +0100 2411707 http://www.medworm.com/index.php?rid=2411706&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F3%2F239%3Frss%3D1 In conclusion, we demonstrate a novel computational framework to systematically dissect transcriptional programs activated by mechanical ventilation in the lung, and show that noninjurious mechanical ventilation initiates a response that can prime the lung for injury from a subsequent insult. (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2411706 Wed, 13 May 2009 04:00:00 +0100 2411706 http://www.medworm.com/index.php?rid=2411705&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F3%2F231%3Frss%3D1 Extraocular muscles (EOMs) are a highly specialized type of tissue with a wide range of unique properties, including characteristic innervation, development, and structural proteins. Even though EOMs are frequently and prominently affected by thyroid-associated diseases, little is known about the direct effects of thyroid hormone on these muscles. To create a comprehensive profile of changes in gene expression levels in EOMs induced by thyroid hormone, hyperthyroid conditions were simulated by treating adult Sprague-Dawley rats with intraperitoneal injections of the thyroid hormone 3,3',5-triiodo-l-thyronine (T3); subsequently, microarray analysis was used to determine changes in mRNA levels in EOMs from T3-treated animals relative to untreated control animals. The expression of 468 transc... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2411705 Wed, 13 May 2009 04:00:00 +0100 2411705 http://www.medworm.com/index.php?rid=2411704&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F3%2F225%3Frss%3D1 We tested the hypothesis that small changes in angiotensin I-converting enzyme (ACE) expression can alter the vascular response to injury. Male mice containing one, two, three, and four copies of the Ace gene with no detectable vascular abnormality or changes in blood pressure were submitted to cuff-induced femoral artery injury. Femoral thickening was higher in 3- and 4-copy mice (42.4 ± 4.3% and 45.7 ± 6.5%, respectively) compared with 1- and 2-copy mice (8.3 ± 1.3% and 8.5 ± 0.9%, respectively). Femoral ACE levels from control and injured vessels were assessed in 1- and 3-copy Ace mice, which represent the extremes of the observed response. ACE vascular activity was higher in 3- vs. 1-copy Ace mice (2.4-fold, P < 0.05) in the control uninjured vessel. Upon... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2411704 Wed, 13 May 2009 04:00:00 +0100 2411704 http://www.medworm.com/index.php?rid=2411703&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F3%2F211%3Frss%3D1 This study provides a thorough database that may serve as a valuable reference tool to develop novel hypotheses aiming to elucidate the biology of ischemic chronic wounds in a preclinical setting. (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2411703 Wed, 13 May 2009 04:00:00 +0100 2411703 http://www.medworm.com/index.php?rid=2411702&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F3%2F199%3Frss%3D1 In this study, we employed a novel drug target validation strategy to uncover the multiple molecular targets of caffeine using combined A2A receptor (A2AR) knockouts (KO) and microarray profiling. Caffeine (10 mg/kg) elicited a distinct profile of striatal gene expression in WT mice compared with that by A2AR gene deletion or by administering caffeine into A2AR KO mice. Thus, A2ARs are required but not sufficient to elicit the striatal gene expression by caffeine (10 mg/kg). Caffeine (50 mg/kg) induced complex expression patterns with three distinct sets of striatal genes: 1) one subset overlapped with those elicited by genetic deletion of A2ARs; 2) the second subset elicited by caffeine in WT as well as A2AR KO mice; and 3) the third subset elicited by caffeine only in A2AR KO mice. Furth... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2411702 Wed, 13 May 2009 04:00:00 +0100 2411702 http://www.medworm.com/index.php?rid=2411701&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F3%2F187%3Frss%3D1 Conclusion: The results highlight new processes involved in lipid handling in liver and will help to understand the complex human pathology providing new proteins and new strategies to cope with hepatic steatosis. (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2411701 Wed, 13 May 2009 04:00:00 +0100 2411701 http://www.medworm.com/index.php?rid=2411700&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F3%2F175%3Frss%3D1 Junctophilins (JPHs) are members of a junctional membrane complex protein family important for the physical approximation of plasmalemmal and sarcoplasmic/endoplasmic reticulum membranes. As such, JPHs facilitate signal transduction in excitable cells between plasmalemmal voltage-gated calcium channels and intracellular calcium release channels. To determine the molecular evolution of the JPH gene family, we performed a phylogenetic analysis of over 60 JPH genes from over 40 species and compared conservation across species and different isoforms. We found that JPHs are evolutionary highly conserved, in particular the membrane occupation and recognition nexus motifs found in all species. Our data suggest that an ancestral form of JPH arose at the latest in a common metazoan ancestor and tha... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2411700 Wed, 13 May 2009 04:00:00 +0100 2411700 http://www.medworm.com/index.php?rid=2411699&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F3%2F164%3Frss%3D1 The study of spontaneous mutations in mice over the last century has been fundamental to our understanding of normal physiology and mechanisms of disease. Here we studied the phenotype and genotype of a novel mouse model we have called the New Zealand Ginger (NZG/Kgm) mouse. NZG/Kgm mice are very large, rapidly growing, ginger-colored mice with pink eyes. Breeding NZG/Kgm mice with CAST/Ei or C57BL/6J mice showed that the ginger coat colour is a recessive trait, while the excessive body weight and large body size exhibit a semidominant pattern of inheritance. Backcrossing F1 (NZG/Kgm x CAST/Ei) to NZG/Kgm mice to produce the N2 generation determined that the NZG/Kgm mouse has two recessive pigmentation variant genes (oca2p and tyrp-1b) and that the tyrp-1b gene locus associates with large ... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2411699 Wed, 13 May 2009 04:00:00 +0100 2411699 http://www.medworm.com/index.php?rid=2411698&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F3%2F149%3Frss%3D1 This study is the first large-scale discovery of bacteria-responsive genes in cod and the first to demonstrate upregulation of IRF1 in fish immune tissues as a result of bacterial antigen stimulation. Given the importance of IRF1 in vertebrate immune responses to viral and bacterial pathogens, the full-length cDNA sequence of Atlantic cod IRF1 was obtained and compared with putative orthologous sequences from other organisms. Functional annotations of assembled SSH library ESTs showed that bacterial antigen stimulation caused changes in many biological processes including chemotaxis, regulation of apoptosis, antimicrobial peptide production, and iron homeostasis. Moreover, differences in spleen and head kidney gene expression responses to the bacterial antigens pointed to a potential role ... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2411698 Wed, 13 May 2009 04:00:00 +0100 2411698 http://www.medworm.com/index.php?rid=2321214&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Ffull%2F37%2F2%2F147%3Frss%3D1 (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2321214 Fri, 10 Apr 2009 04:00:00 +0100 2321214 http://www.medworm.com/index.php?rid=2321213&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F2%2F140%3Frss%3D1 The tet-inducible system has been widely used to achieve conditional gene expression in genetically modified mice. To alleviate the frequent difficulties associated with recovery of relevant transgenic founders, we tested whether a controlled strategy of transgenesis would support reliable cell-specific, doxycycline (Dox)-controlled transgene expression in vivo. Taking advantage of the potent hypoxanthine-aminopterin-thymidine selection strategy and an embryonic stem (ES) cell line supporting efficient germ-line transmission, we used hypoxanthine phosphoribosyltransferase (HPRT) targeting to insert a single copy tet-inducible construct designed to allow both glucocorticoid receptor (GR) and β-galactosidase (β-Gal) expression. Conditional, Dox-dependent GR and β-Gal expressio... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2321213 Fri, 10 Apr 2009 04:00:00 +0100 2321213 http://www.medworm.com/index.php?rid=2321212&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F2%2F133%3Frss%3D1 The acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) was described 30 yr ago, yet making a definitive diagnosis remains difficult. The identification of biomarkers obtained from peripheral blood could provide additional noninvasive means for diagnosis. To identify gene expression profiles that may be used to classify patients with ALI, 13 patients with ALI + sepsis and 20 patients with sepsis alone were recruited from the Medical Intensive Care Unit of the University of Pittsburgh Medical Center, and microarrays were performed on peripheral blood samples. Several classification algorithms were used to develop a gene signature for ALI from gene expression profiles. This signature was validated in an independently obtained set of patients with ALI + sepsis (n = 8) and sepsi... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2321212 Fri, 10 Apr 2009 04:00:00 +0100 2321212 http://www.medworm.com/index.php?rid=2321211&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F2%2F119%3Frss%3D1 Mdx mice show a milder phenotype than Duchenne patients despite bearing an analogous genetic defect. Our aim was to sort out genes, differentially expressed during the evolution of skeletal muscle mdx mouse disease, to elucidate the mechanisms by which these animals overcome the lack of dystrophin. Genome-wide microarray-based gene expression analysis was carried out at 3 wk and 1.5 and 3 mo of life. Candidate genes were selected by comparing: 1) mdx vs. controls at each point in time, and 2) mdx mice and 3) control mice among the three points in time. The first analysis showed a strong upregulation (96%) of inflammation-related genes and in >75% of genes related to cell adhesion, muscle structure/regeneration, and extracellular matrix remodeling during mdx disease evolution. Lgals3, Po... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2321211 Fri, 10 Apr 2009 04:00:00 +0100 2321211 http://www.medworm.com/index.php?rid=2321210&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F2%2F108%3Frss%3D1 We conducted a large-scale gene expression screen using the 3,200 cDNA probe microarray developed specifically for Ursus americanus to detect expression differences in liver and skeletal muscle that occur during winter hibernation compared with animals sampled during summer. The expression of 12 genes, including RNA binding protein motif 3 (Rbm3), that are mostly involved in protein biosynthesis, was induced during hibernation in both liver and muscle. The Gene Ontology and Gene Set Enrichment analysis consistently showed a highly significant enrichment of the protein biosynthesis category by overexpressed genes in both liver and skeletal muscle during hibernation. Coordinated induction in transcriptional level of genes involved in protein biosynthesis is a distinctive feature of the trans... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2321210 Fri, 10 Apr 2009 04:00:00 +0100 2321210 http://www.medworm.com/index.php?rid=2321208&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F2%2F99%3Frss%3D1 The influence of Glu298Asp endothelial nitric oxide synthase (eNOS) polymorphism in exercise-induced reflex muscle vasodilatation is unknown. We hypothesized that nonexercising forearm blood flow (FBF) responses during handgrip isometric exercise would be attenuated in individuals carrying the Asp298 allele. In addition, these responses would be mediated by reduced eNOS function and NO-mediated vasodilatation or sympathetic vasoconstriction. From 287 volunteers previously genotyped, we selected 33 healthy individuals to represent three genotypes: Glu/Glu [n = 15, age 43 ± 3 yr, body mass index (BMI) 22.9 ± 0.3 kg/m2], Glu/Asp (n = 9, age 41 ± 3 yr, BMI 23.7 ± 1.0 kg/m2), and Asp/Asp (n = 9, age 40 ± 4 yr, BMI 23.5 ± 0.9 kg/m2). Heart rate (HR), mea... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2321208 Fri, 10 Apr 2009 04:00:00 +0100 2321208 http://www.medworm.com/index.php?rid=2321206&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F2%2F88%3Frss%3D1 In conclusion, the regulatory response of identified proteins may help to explain development and consequences of hepatic lipidosis but also offers novel candidates potentially involved in signaling for maintaining energy homeostasis. (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2321206 Fri, 10 Apr 2009 04:00:00 +0100 2321206 http://www.medworm.com/index.php?rid=2321204&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F2%2F79%3Frss%3D1 To elucidate the physiological responses to a social stressor, we exposed mice to an isolation stress and analyzed their hepatic gene expression profiles using a DNA microarray. Male BALB/c mice were exposed to isolation stress for 30 days, and then hepatic RNA was sampled and subjected to DNA microarray analysis. The isolation stress altered the expression of 420 genes (after considering the false discovery rate). Gene Ontology analysis of these differentially expressed genes indicated that the stress remarkably downregulated the lipid metabolism-related pathway through peroxisome proliferator-activated receptor-, while the lipid biosynthesis pathway controlled by sterol regulatory element binding factor 1, Golgi vesicle transport, and secretory pathway-related genes were significantly up... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2321204 Fri, 10 Apr 2009 04:00:00 +0100 2321204 http://www.medworm.com/index.php?rid=2321202&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F2%2F67%3Frss%3D1 The cellular composition and morphology of the stomach epithelium have been described in detail; however, the molecular mechanisms that regulate the differentiation of the various cell lineages as well as the function of mature gastric cells are far less clear. Recently, dissection of the molecular anatomy of the stomach has been boosted by the advent of functional genomics, which allows investigators to determine patterns of gene expression across virtually the entire cellular transcriptome. In this review, we discuss the impact of functional genomic studies on the understanding of gastric epithelial physiology. We show how functional genomic studies have uncovered genes that are useful as new cell lineage-specific markers of differentiation and provide new insights into cell physiology. ... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2321202 Fri, 10 Apr 2009 04:00:00 +0100 2321202 http://www.medworm.com/index.php?rid=2231590&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F1%2F58%3Frss%3D1 p53 is a tumor suppressor protein that also plays a role in regulating aerobic metabolism. Since skeletal muscle is a major source of whole body aerobic respiration, it is important to delineate the effects of p53 on muscle metabolism. In p53 knockout (KO) mice, we observed diminished mitochondrial content in mixed muscle and lowered peroxisome proliferator-activated receptor- (PPAR) coactivator (PGC)-1 protein levels in gastrocnemius muscle. In intermyofibrillar (IMF) mitochondria, lack of p53 was associated with reduced respiration and elevated reactive oxygen species production. Permeability transition pore kinetics remained unchanged; however, IMF mitochondrial cytochrome c release was reduced and DNA fragmentation was lowered, illustrating a resistance to mitochondrially driven apopto... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2231590 Tue, 03 Mar 2009 05:00:00 +0100 2231590 http://www.medworm.com/index.php?rid=2231589&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F1%2F52%3Frss%3D1 To dissect the genetic architecture controlling blood pressure (BP) regulation in the spontaneously hypertensive rat (SHR) we derived congenic rat strains for four previously mapped BP quantitative trait loci (QTLs) in chromosomes 2, 4, and 16. Target chromosomal regions from the Brown Norway rat (BN) averaging 13–29 cM were introgressed by marker-assisted breeding onto the SHR genome in 12 or 13 generations. Under normal salt intake, QTLs on chromosomes 2a, 2c, and 4 were associated with significant changes in systolic BP (13, 20, and 15 mmHg, respectively), whereas the QTL on chromosome 16 had no measurable effect. On high salt intake (1% NaCl in drinking water for 2 wk), the chromosome 16 QTL had a marked impact on SBP, as did the QTLs on chromosome 2a and 2c (18, 17, and 19 mmHg,... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2231589 Tue, 03 Mar 2009 05:00:00 +0100 2231589 http://www.medworm.com/index.php?rid=2231588&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F1%2F43%3Frss%3D1 A hallmark of hibernation in mammals is metabolic flexibility, which is typified by reversible bouts of metabolic depression (torpor) and the seasonal shift from predominantly carbohydrate to lipid metabolism from summer to winter. To provide new insight into the control and consequences of hibernation, we used LC/MS-based metabolomics to measure differences in small molecules in ground squirrel liver in five activity states: summer, entering torpor, late torpor, arousing from torpor, and interbout arousal. There were significant alterations both seasonally and within torpor-arousal cycles in enzyme cofactor metabolism, amino acid catabolism, and purine and pyrimidine metabolism, with observed metabolites reduced during torpor and increased upon arousal. Multiple lipids also changed, inclu... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2231588 Tue, 03 Mar 2009 05:00:00 +0100 2231588 http://www.medworm.com/index.php?rid=2231587&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F1%2F35%3Frss%3D1 The extraocular muscles (EOMs) are a distinct muscle group that displays an array of unique contractile, structural, and regenerative properties. They also have differential sensitivity to certain diseases and are enigmatically spared in Duchenne muscular dystrophy (DMD). The EOMs are so distinct from other skeletal muscles that the term "allotype" has been coined to highlight EOM group-specific properties. We hypothesized that increased and distinct stem cells may underlie the continual myogenesis noted in EOM. The side population (SP) stem cells were isolated and studied. EOMs had 15x higher SP cell content compared with limb muscles. Expression profiling revealed 348 transcripts that define the EOM-SP transcriptome. Over 92% of transcripts were SP specific, because they were absent in p... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2231587 Tue, 03 Mar 2009 05:00:00 +0100 2231587 http://www.medworm.com/index.php?rid=2231586&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F1%2F23%3Frss%3D1 In conclusion, transduction of reporter genes into MSCs preserved the basic properties of stem cells while enabling noninvasive imaging in living animals to study the biodistribution and other biological activities of the cells. (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2231586 Tue, 03 Mar 2009 05:00:00 +0100 2231586 http://www.medworm.com/index.php?rid=2231585&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F1%2F12%3Frss%3D1 The molecular physiology underlying human milk production is largely unknown because of limitations in obtaining tissue samples. Determining gene expression in normal lactating women would be a potential step toward understanding why some women struggle with or fail at breastfeeding their infants. Recently, we demonstrated the utility of RNA obtained from breast milk fat globule (MFG) to detect mammary epithelial cell (MEC)-specific gene expression. We used MFG RNA to determine the gene expression profile of human MEC during lactation. Microarray studies were performed using Human Ref-8 BeadChip arrays (Illumina). MFG RNA was collected every 3 h for 24 h from five healthy, exclusively breastfeeding women. We determined that 14,070 transcripts were expressed and represented the MFG transcri... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2231585 Tue, 03 Mar 2009 05:00:00 +0100 2231585 http://www.medworm.com/index.php?rid=2231584&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F37%2F1%2F1%3Frss%3D1 To regulate their internal environments, organisms must adapt to varying ion levels in their diet. Adult Drosophila were exposed to dietary salt stress, and their physiological, survival, and gene expression responses monitored. Insects continued to feed on NaCl-elevated diet, although levels >4% wt/vol ultimately proved fatal. Affymetrix microarray analysis of flies fed on diet containing elevated NaCl showed a phased response: the earliest response was widespread upregulation of immune genes, followed by upregulation of carbohydrate metabolism as the immune response was downregulated, then finally a switch to amino acid catabolism and inhibition of genes associated with the reproductive axis. Significantly, the online transcriptomic resource FlyAtlas reports that most of the modulated... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2231584 Tue, 03 Mar 2009 05:00:00 +0100 2231584 http://www.medworm.com/index.php?rid=2152580&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F3%2F167%3Frss%3D1 Identifying genotypes and phenotypes that enhance an organism's ability to survive stress is of interest. We used Caenorhabditis elegans mutants, RNA interference (RNAi), and the chemical 5-fluorodeoxyuridine (FUDR) to test the hypothesis that a reduction in progeny would increase oxygen deprivation (anoxia) survival. In the hermaphrodite gonad, germ line processes such as spermatogenesis and oogenesis can be simultaneously as well as independently disrupted by genetic mutations. We analyzed genetic mutants [glp-1(q158), glp-4(bn2ts), plc-1(rx1), ksr-1(ku68), fog-2(q71), fem-3(q20), spe-9(hc52ts), fer-15(hc15ts)] with reduced progeny production due to various reproductive defects. Furthermore, we used RNAi to inhibit the function of gene products in the RTK/Ras/MAPK signaling pathway, whic... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2152580 Mon, 02 Feb 2009 05:00:00 +0100 2152580 http://www.medworm.com/index.php?rid=2152579&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F3%2F158%3Frss%3D1 A quantitative trait locus (QTL) approach was used to define the genetic architecture underlying variation in systolic blood pressure (SBP) and heart rate (HR), measured indirectly on seven occasions by the tail cuff procedure. The tests were conducted in 395 F2 adult mice (197 males, 198 females) derived from a cross of the C57BL/6J (B6) and DBA/2J (D2) strains and in 22 BXD recombinant-inbred (RI) strains. Interval mapping of F2 data for the first 5 days of measurement nominated one statistically significant and one suggestive QTL for SBP on chromosomes (Chr) 4 and 14, respectively, and two statistically significant QTL for HR on Chr 1 (which was specific to female mice) and Chr 5. New suggestive QTL emerged for SBP on Chr 3 (female-specific) and 8 and for HR on Chr 11 for measurements r... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2152579 Mon, 02 Feb 2009 05:00:00 +0100 2152579 http://www.medworm.com/index.php?rid=2152578&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F3%2F149%3Frss%3D1 Endurance exercise (EE) leads to beneficial alterations in skeletal muscle lipid metabolism in overweight and obese individuals; however, the mechanisms of these improvements are poorly understood. The primary goal of the current investigation was to test the hypothesis that long-term EE training (6 mo) leads to alterations in the mRNA abundance of key lipid metabolism enzymes in skeletal muscle of overweight and obese middle-aged women and men. A secondary aim of this study was to investigate the hypothesis that exercise-mediated adaptations in mRNA levels differ between women and men. The mRNA abundance of representative lipogenic and lipolytic genes from major lipid metabolism pathways, as well as representative lipogenic and lipolytic transcription factors, were determined by real-time... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2152578 Mon, 02 Feb 2009 05:00:00 +0100 2152578 http://www.medworm.com/index.php?rid=2152577&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F3%2F140%3Frss%3D1 The objective of this study was to characterize conceptus gene expression during trophoblastic elongation and the early attachment to the uterine endometrium on days 11–14 of gestation with the GeneChip Porcine Genome Array. In all, 3,759 different probe sets were statistically different in at least one comparison [spherical vs. tubular, spherical vs. day 12 filamentous (D12F), spherical vs. day 14 filamentous (D14F), tubular vs. D12F, tubular vs. D14F, and D12F vs. D14F]. When restricted to the spherical vs. D12F and D12F vs. D14F comparisons, 482 and 232 genes, respectively, were statistically different with greater than twofold change in expression. Utilization of k-means clustering, in addition to the Database for Annotation, Visualization, and Integrated Discovery (DAVID), ident... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2152577 Mon, 02 Feb 2009 05:00:00 +0100 2152577 http://www.medworm.com/index.php?rid=2152576&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F3%2F129%3Frss%3D1 The consequences of viral infection during pregnancy include impact on fetal and maternal immune responses and on fetal development. Transplacental infection in cattle with noncytopathic bovine viral diarrhea virus (ncpBVDV) during early gestation results in persistently infected (PI) fetuses with life-long viremia and susceptibility to infections. Infection of the fetus during the third trimester or after birth leads to a transient infection cleared by a competent immune system. We hypothesized that ncpBVDV infection and presence of an infected fetus would alter immune response and lead to downregulation of proinflammatory processes in pregnant dams. Naïve pregnant heifers were challenged with ncpBVDV2 on day 75 (PI fetus) and day 175 [transiently infected (TI) fetus] or kept uninfec... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2152576 Mon, 02 Feb 2009 05:00:00 +0100 2152576 http://www.medworm.com/index.php?rid=2089490&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Ffull%2F36%2F2%2F127%3Frss%3D1 (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2089490 Thu, 08 Jan 2009 05:00:00 +0100 2089490 http://www.medworm.com/index.php?rid=2089489&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F2%2F114%3Frss%3D1 We examined the high body weight-selected mouse lines NMRI8 and DU6i and the intercross populations NMRI8 x DBA/2 and DU6i x DBA/2. Structural models help us understand whether genetic factors affect lean mass and fat mass pleiotropically or nonpleiotropically. Sex has direct effects on both fat and muscle weight but also influences fat weight indirectly via muscle weight. Three genetic loci identified in these two crosses showed exclusive effects on fat deposition, and five loci contributed exclusively to muscle weight. Two additional loci showed pleiotropic effects on fat and muscle weight, with one locus acting in both crosses. Fat weight and muscle weight were influenced by epistatic effects. We provide evidence that significant fat loci in strains selected for body weight contribute t... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2089489 Thu, 08 Jan 2009 05:00:00 +0100 2089489 http://www.medworm.com/index.php?rid=2089488&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F2%2F98%3Frss%3D1 Early mammalian development is characterized by extensive changes in nuclear functions that result from epigenetic modifications of the newly formed embryonic genome. While the first embryonic cells are totipotent, this status spans only a few cell cycles. At the blastocyst stage, the embryo already contains differentiated trophectoderm cells and pluripotent inner cell mass cells. Concomitantly, the embryonic genome becomes progressively transcriptionally active. During this unique period of development, the gene expression pattern has been mainly characterized in the mouse, in which embryonic genome activation (EGA) spans a single cell cycle after abrupt epigenetic modifications. To further characterize this period, we chose to analyze it in the rabbit, in which, as in most mammals, EGA i... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2089488 Thu, 08 Jan 2009 05:00:00 +0100 2089488 http://www.medworm.com/index.php?rid=2089487&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F2%2F89%3Frss%3D1 The process of parturition involves the complex interplay of factors that change the excitability and contractile activity of the uterus. We have compared the relative gene expression profile of myometrium from rats before parturition (21 days pregnant) and during delivery, using high-density DNA microarray. Of 8,740 sequences available in the array, a total of 3,782 were detected as present. From the sequences that were significantly altered, 59 genes were upregulated and 82 genes were downregulated. We were able to detect changes in genes described to have altered expression level at term, including connexin 43 and 26, cyclooxygenase 2, and oxytocin receptor, as well as novel genes that have been not previously associated with parturition. Quantitative real-time PCR on selected genes fur... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2089487 Thu, 08 Jan 2009 05:00:00 +0100 2089487 http://www.medworm.com/index.php?rid=2089486&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F2%2F79%3Frss%3D1 A genome-wide linkage scan for endurance training-induced changes in stroke volume detected a quantitative trait locus on chromosome 10p11 in white families of the HERITAGE Family Study. Dense microsatellite mapping narrowed down the linkage region to a 7 Mb area containing 16 known and 14 predicted genes. Association analyses with 90 single nucleotide polymorphisms (SNPs) provided suggestive evidence (P values from 0.03 to 0.06) for association in the kinesin heavy chain (KIF5B) gene locus in the whole cohort. The associations at the KIF5B locus were stronger (P values from 0.001 to 0.008) when the analyses were performed on linkage-informative families only (family-specific logarithm of the odds ratio scores >0.025 at peak linkage location). Resequencing the coding and regulatory regi... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2089486 Thu, 08 Jan 2009 05:00:00 +0100 2089486 http://www.medworm.com/index.php?rid=2089485&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F2%2F69%3Frss%3D1 Communication between endothelial and mural cells (smooth muscle cells, pericytes, and fibroblasts) can dictate blood vessel size and shape during angiogenesis, and control the functional aspects of mature blood vessels, by determining things such as contractile properties. The ability of these different cell types to regulate each other's activities led us to ask how their interactions directly modulate gene expression. To address this, we utilized a three-dimensional model of angiogenesis and screened for genes whose expression was altered under coculture conditions. Using a BeadChip array, we identified 323 genes that were uniquely regulated when endothelial cells and mural cells (fibroblasts) were cultured together. Data mining tools revealed that differential expression of genes from ... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2089485 Thu, 08 Jan 2009 05:00:00 +0100 2089485 http://www.medworm.com/index.php?rid=2089484&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F2%2F61%3Frss%3D1 The crucian carp, Carassius carassius, survives days to months without oxygen, depending on temperature. In the anoxic crucian carp brain, increased GABAergic inhibition, mediated by increased extracellular levels of GABA, has been shown to suppress electric activity and ATP consumption. To investigate an involvement of gene expression in this response, we utilized real-time RT-PCR to test the effect of 1 and 7 days anoxia (8°C) on the expression of 22 genes, including nine GABAA receptor subunits (1–6, β2, , and 2), three GABAB receptor subunits (GB1a-1b and GB2), three enzymes involved in GABA metabolism (GAD65 and GAD67, GABAT), four GABA transporters (GAT1, 2a-b and 3), two GABAA receptor-associated proteins (GABARAP 1 and 2), and the K+/Cl– cotransporter KCC2. Whi... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2089484 Thu, 08 Jan 2009 05:00:00 +0100 2089484 http://www.medworm.com/index.php?rid=2089483&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Ffull%2F36%2F2%2F59%3Frss%3D1 (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2089483 Thu, 08 Jan 2009 05:00:00 +0100 2089483 http://www.medworm.com/index.php?rid=2032686&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F1%2F52%3Frss%3D1 The Dahl salt-sensitive rat is a widely used model of human salt-sensitive forms of hypertension. The kidney plays an important role in the pathogenesis of Dahl salt-sensitive hypertension, but the molecular mechanisms involved remain a subject of intensive investigation. Gene expression profiling studies suggested that 11β-hydroxysteroid dehydrogenase type 1 might be dysregulated in the renal medulla of Dahl salt-sensitive rats. Additional analysis confirmed that renal medullary expression of 11β-hydroxysteroid dehydrogenase type 1 was downregulated by a high-salt diet in SS-13BN rats, a consomic rat strain with reduced blood pressure salt sensitivity, but not in Dahl salt-sensitive rats. 11β-Hydroxysteroid dehydrogenase type 1 is known to convert inactive 11-dehydrocortico... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2032686 Fri, 12 Dec 2008 05:00:00 +0100 2032686 http://www.medworm.com/index.php?rid=2032685&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F1%2F43%3Frss%3D1 In insulin-resistant status such as obesity, failure of pancreatic islets to increase insulin secretion leads to diabetes. We sought to screen for the islet genes that facilitate islet adaptation to obesity by comparing gene expression profiles between two strains of obesity-prone inbred mice with different propensities for hyperglycemia. C57BL/6J and AKR/J were fed regular rodent chow or high-fat diet, after which islet morphology, secretory function, and gene expression were assessed. AKR/J had lower blood glucose and higher insulin levels compared with C57BL/6J mice on regular rodent chow or high-fat diet. Insulin secretion was 3.2-fold higher in AKR/J than C57BL/6J mice following intraperitoneal glucose injection. Likewise, glucose-stimulated insulin secretion from isolated islets was ... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2032685 Fri, 12 Dec 2008 05:00:00 +0100 2032685 http://www.medworm.com/index.php?rid=2032684&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F1%2F35%3Frss%3D1 In this study we tracked the development of LVH by echocardiography and analyzed changes in cardiac function and morphology with aging in the SS-16BN/Mcwi, SS/Mcwi, and BN to determine if the consomic SS-16BN/Mcwi was a model of hypertrophic cardiomyopathy (HCM). Aging SS-16BN/Mcwi rats showed no evidence of heart failure or impaired cardiac function upon extensive analysis of left ventricle function by echocardiography and pressure-volume relationships, while their parental SS/Mcwi experienced deterioration in function between 18 and 36 wk of age. In addition aging SS-16BN/Mcwi did not exhibit tissue remodeling common to pathological hypertrophy and HCM such as increased fibrosis and reduced capillary density in the myocardium. In fact, SS-16BN/Mcwi were better protected from developing L... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2032684 Fri, 12 Dec 2008 05:00:00 +0100 2032684 http://www.medworm.com/index.php?rid=2032683&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F1%2F24%3Frss%3D1 Conclusions: intermittent and sustained hypoxia induced distinct gene expression patterns in rat lungs. The functional characteristics of genes activated by these two distinct perturbations suggest their roles in the downstream physiological effects of intermittent and sustained hypoxia. Our results demonstrate the discovery potential of applying systems biology approaches to the understanding of mechanisms underlying hypoxic lung response. (Source: Physiological Genomics) Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2032683 Fri, 12 Dec 2008 05:00:00 +0100 2032683 http://www.medworm.com/index.php?rid=2032682&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F1%2F15%3Frss%3D1 Peroxisome proliferator-activated receptor (PPAR) regulates lipid metabolism at the transcriptional level and modulates the expression of genes involved in inflammation, cell proliferation, and differentiation. Although PPAR has been shown to mitigate cardiac hypertrophy, knowledge about underlying mechanisms and the nature of signaling pathways involved is fragmentary and incomplete. The aim of this study was to identify the processes and signaling pathways regulated by PPAR in hearts challenged by a chronic pressure overload by means of whole genome transcriptomic analysis. PPAR–/– and wild-type mice were subjected to transverse aortic constriction (TAC) for 28 days, and left ventricular gene expression profile was determined with Affymetrix GeneChip Mouse Genome 430 2.0 arra... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2032682 Fri, 12 Dec 2008 05:00:00 +0100 2032682 http://www.medworm.com/index.php?rid=2032681&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F36%2F1%2F1%3Frss%3D1 Studies were performed to examine the extent to which mechanical stimuli mediate control of angiogenesis in bladder cells both in vitro and in vivo. Differential gene expression between control nonstretched and cyclically stretched bladder smooth muscle cells was assessed using oligonucleotide microarrays and pathway analysis by the web tool Fast Assignment and Transference of Information (FatiGO). Data showed that a substantial proportion (33 of 86) of mechanically responsive genes were angiogenesis-related and include cytokines, growth-related factors, adhesion proteins, and matricellular, signal transduction, extracellular matrix (ECM), and inflammatory molecules. Integrative knowledge of protein-protein interactions revealed that 12 mechano-sensitive gene-encoded proteins have interact... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=2032681 Fri, 12 Dec 2008 05:00:00 +0100 2032681 http://www.medworm.com/index.php?rid=1954888&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F35%2F3%2F341%3Frss%3D1 The anx/anx mouse displays poor appetite and lean appearance and is considered a good model for the study of anorexia nervosa. To identify new genes involved in feeding behavior and body weight regulation we performed an expression profiling in the hypothalamus of the anx/anx mice. Using commercial microarrays we detected 156 differentially expressed genes and validated 92 of those using TaqMan low-density arrays. The expression of a set of 87 candidate genes selected based on literature evidences was also quantified by TaqMan low-density arrays. Our results showed enrichment in deregulated genes involved in cell death, cell morphology, and cancer, as well as an alteration of several signaling circuits involved in energy balance including neuropeptide Y and melanocortin signaling. The expr... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=1954888 Wed, 12 Nov 2008 05:00:00 +0100 1954888 http://www.medworm.com/index.php?rid=1954887&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F35%2F3%2F330%3Frss%3D1 To address the multiplicity of the renin-angiotensin system (RAS) with particular interest in its local, synergistic regulation, we investigate dynamic changes of the RAS and associated systems in response to external stimuli in the rat. We tested influences of the RAS blockade (candesartan and enalapril), diuretics (hydrochlorothiazide), high lipid diet, and salt loading on tissue mRNA level of 12 principal genes. Under the hemodynamic conditions appropriately predetermined, we quantitatively evaluated mRNA level changes with and without each intervention in five organs–the brain, heart, kidney, liver, and adipose tissues–of male rats (n = 5 each). A total of 250 tissues were examined by real-time PCR. Significant changes in mRNA level (P < 0.05) were found in a drug-, diet... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=1954887 Wed, 12 Nov 2008 05:00:00 +0100 1954887 http://www.medworm.com/index.php?rid=1954886&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F35%2F3%2F316%3Frss%3D1 Aside from abnormal angiogenesis, dual endothelin-1/VEGF signal peptide-activated receptor deficiency (DEspR–/–) results in aberrant neuroepithelium and neural tube differentiation, thus elucidating DEspR's role in neurogenesis. With the emerging importance of neurogenesis in adulthood, we tested the hypothesis that nonembryonic-lethal DEspR haploinsufficiency (DEspR+/–) perturbs neuronal homeostasis, thereby facilitating aging-associated neurodegeneration. Here we show that, in male mice only, DEspR-haploinsufficiency impaired hippocampus-dependent visuospatial and associative learning and induced noninflammatory spongiform changes, neuronal vacuolation, and loss in the hippocampus, cerebral cortex, and subcortical regions, consistent with autophagic cell death. In contr... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=1954886 Wed, 12 Nov 2008 05:00:00 +0100 1954886 http://www.medworm.com/index.php?rid=1954885&cid=s_33710_50_f&fid=33710&url=http%3A%2F%2Fphysiolgenomics.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F35%2F3%2F305%3Frss%3D1 Heart failure is a complex, complicated disease that is not yet fully understood. We used the Module Map algorithm to uncover groups of genes that have a similar pattern of expression under various conditions of heart stress. These groups of genes are called modules and may serve as computational predictions of biological pathways for the various clinical situations. The Module Map algorithm allows a large-scale analysis of genes expressed. We applied this algorithm to 700 different mouse experiments downloaded from the Gene Expression Omnibus database, which identified 884 modules. The analysis reconstructed partially known principles that play a role in governing the response of heart to stress, thus demonstrating the strength of the method. We have shown a role of genes related to the i... Physiological Genomics journals http://www.medworm.com/rss/comments.php?id=1954885 Wed, 12 Nov 2008 05:00:00 +0100 1954885