Left ventricle transcriptomic analysis reveals connective tissue accumulation associates with initial age-dependent decline in VO2peak from its lifetime apex
Peak oxygen consumption (Vo2peak) strongly predicts morbidity and mortality better than other established risk factors, yet mechanisms associated with its age-associated decline are unknown. Our laboratory has shown that Vo2peak first begins to decrease at the same age of 19–20 wk in both sedentary and wheel-running, female Wistar rats (Toedebusch et al., Physiol Genomics. 48: 101–115, 2016). Here, we employed a total systemic approach using unsupervised interrogation of mRNA with RNA sequencing. The purpose of our study was to analyze transcriptomic profiles from both sedentary (SED) and wheel-running (RUN) co...
Source: Physiological Genomics - January 9, 2017 Category: Genetics & Stem Cells Authors: Ruegsegger, G. N., Toedebusch, R. G., Braselton, J. F., Childs, T. E., Booth, F. W. Tags: Research Articles Source Type: research
Glucose regulates the intrinsic inflammatory response of the heart to surgically induced hypothermic ischemic arrest and reperfusion
We investigated the isolated working rat heart as a model to study early transcriptional remodeling induced in the setting of open heart surgery and stress hyperglycemia. Hearts of male Sprague Dawley rats were cold-arrested in Krebs-Henseleit buffer and subjected to 60 min normothermic reperfusion in the working mode with buffer supplemented with noncarbohydrate substrates plus glucose (25 mM) or mannitol (25 mM; osmotic control). Gene expression profiles were determined by microarray analysis and compared with those of nonperfused hearts. Perfused hearts displayed a transcriptional signature independent from the presence...
Source: Physiological Genomics - January 9, 2017 Category: Genetics & Stem Cells Authors: Bux, A. S., Lindsey, M. L., Vasquez, H. G., Taegtmeyer, H., Harmancey, R. Tags: Research Articles Source Type: research
Elevated K+ channel activity opposes vasoconstrictor response to serotonin in cerebral arteries of the Fawn Hooded Hypertensive rat
Previous studies suggest that middle cerebral arteries (MCAs) of Fawn Hooded Hypertensive (FHH) rats exhibit impaired myogenic response and introgression of a small region of Brown Norway chromosome 1 containing 15 genes restored the response in FHH.1BN congenic rat. The impaired myogenic response in FHH rats is associated with an increase in the activity of the large conductance potassium (BK) channel in vascular smooth muscle cells (VSMCs). The present study examined whether the increased BK channel function in FHH rat alters vasoconstrictor response to serotonin (5-HT). Basal myogenic tone and spontaneous myogenic respo...
Source: Physiological Genomics - December 31, 2016 Category: Genetics & Stem Cells Authors: Pabbidi, M. R., Roman, R. J. Tags: Research Articles Source Type: research
Pattern analysis uncovers a chronic ethanol-induced disruption of the switch-like dynamics of C/EBP-{beta} and C/EBP-{alpha} genome-wide binding during liver regeneration
Chronic ethanol intake impairs liver regeneration through a system-wide alteration in the regulatory networks driving the response to injury. Our study focused on the initial phase of response to 2/3rd partial hepatectomy (PHx) to investigate how adaptation to chronic ethanol intake affects the genome-wide binding profiles of the transcription factors C/EBP-β and C/EBP-α. These factors participate in complementary and often opposing functions for maintaining cellular differentiation, regulating metabolism, and governing cell growth during liver regeneration. We analyzed ChIP-seq data with a comparative pattern c...
Source: Physiological Genomics - December 31, 2016 Category: Genetics & Stem Cells Authors: Kuttippurathu, L., Patra, B., Cook, D., Hoek, J. B., Vadigepalli, R. Tags: Research Articles Source Type: research
Biological roles of microRNAs in the control of insulin secretion and action
microRNAs (miRNAs) are intracellular and circulating molecular components contributing to genome expression control through binding mRNA targets, which generally results in downregulated mRNA expression. One miRNA can target several mRNAs, and one transcript can be targeted by several miRNAs, resulting in complex fine-tuning of regulation of gene networks and signaling pathways. miRNAs regulate metabolism, adipocyte differentiation, pancreatic development, β-cell mass, insulin biosynthesis, secretion, and signaling, and their role in diabetes and obesity is emerging. Their pathophysiological effects are essentially de...
Source: Physiological Genomics - December 31, 2016 Category: Genetics & Stem Cells Authors: Calderari, S., Diawara, M. R., Garaud, A., Gauguier, D. Tags: Review Source Type: research
Corrigendum
(Source: Physiological Genomics)
Source: Physiological Genomics - December 18, 2016 Category: Genetics & Stem Cells Tags: Corrigendum Source Type: research
Cigarette smoking causes epigenetic changes associated with cardiorenal fibrosis
Clinical studies indicate that smoking combustible cigarettes promotes progression of renal and cardiac injury, leading to functional decline in the setting of chronic kidney disease (CKD). However, basic studies using in vivo small animal models that mimic clinical pathology of CKD are lacking. To address this issue, we evaluated renal and cardiac injury progression and functional changes induced by 4 wk of daily combustible cigarette smoke exposure in the 5/6th partial nephrectomy (PNx) CKD model. Molecular evaluations revealed that cigarette smoke significantly (P < 0.05) decreased renal and cardiac expression of the...
Source: Physiological Genomics - December 18, 2016 Category: Genetics & Stem Cells Authors: Drummond, C. A., Crotty Alexander, L. E., Haller, S. T., Fan, X., Xie, J. X., Kennedy, D. J., Liu, J., Yan, Y., Hernandez, D.-A., Mathew, D. P., Cooper, C. J., Shapiro, J. I., Tian, J. Tags: Genomic and ' Polyomic Studies of Cardiovascular and Inflammatory Diseases Source Type: research
Partial deficiency of CTRP12 alters hepatic lipid metabolism
Secreted hormones play pivotal roles in tissue cross talk to maintain physiologic blood glucose and lipid levels. We previously showed that C1q/TNF-related protein 12 (CTRP12) is a novel secreted protein involved in regulating glucose metabolism whose circulating levels are reduced in obese and insulin-resistant mouse models. Its role in lipid metabolism, however, is unknown. Using a novel heterozygous mouse model, we show that the loss of a single copy of the Ctrp12 gene (also known as Fam132a and adipolin) affects whole body lipid metabolism. In Ctrp12 (+/–) male mice fed a control low-fat diet, hepatic fat oxidati...
Source: Physiological Genomics - December 18, 2016 Category: Genetics & Stem Cells Authors: Tan, S. Y., Little, H. C., Lei, X., Li, S., Rodriguez, S., Wong, G. W. Tags: General Interest Source Type: research
Expression profile of hepatic genes related to lipid homeostasis in LSR heterozygous mice contributes to their increased response to high-fat diet
Perturbations of lipid homeostasis manifest as dyslipidemias and obesity, which are significant risk factors for atherosclerosis and diabetes. Lipoprotein receptors in the liver are key players in the regulation of lipid homeostasis, among which the hepatic lipolysis stimulated lipoprotein receptor, LSR, was recently shown to play an important role in the removal of lipoproteins from the circulation during the postprandial phase. Since heterozygous LSR+/– mice demonstrate moderate dyslipidemia and develop higher body weight gain in response to high-fat diet compared with littermate LSR+/+ controls, we questioned if L...
Source: Physiological Genomics - December 12, 2016 Category: Genetics & Stem Cells Authors: Akbar, S., Pincon, A., Lanhers, M.-C., Claudepierre, T., Corbier, C., Gregory-Pauron, L., Malaplate-Armand, C., Visvikis, A., Oster, T., Yen, F. T. Tags: Genomics of Metabolic and Tumor/Cancer Traits Source Type: research
Establishing the involvement of the novel gene AGBL5 in retinitis pigmentosa by whole genome sequencing
In this study we sought to identify the underlying cause of IRD in a family by whole genome sequence (WGS) analysis. Clinical characterization including standard ophthalmic examination, fundus photography, visual field testing, electroretinography, and review of medical and family history was performed. WGS was performed on affected and unaffected family members using Illumina HiSeq X10. Sequence reads were aligned to hg19 using BWA-MEM and variant calling was performed with Genome Analysis Toolkit. The called variants were annotated with SnpEff v4.11, PolyPhen v2.2.2, and CADD v1.3. Copy number variations were called usin...
Source: Physiological Genomics - December 12, 2016 Category: Genetics & Stem Cells Authors: Branham, K., Matsui, H., Biswas, P., Guru, A. A., Hicks, M., Suk, J. J., Li, H., Jakubosky, D., Long, T., Telenti, A., Nariai, N., Heckenlively, J. R., Frazer, K. A., Sieving, P. A., Ayyagari, R. Tags: General Interest Source Type: research
Impact of MYH6 variants in hypoplastic left heart syndrome
Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). Although prior studies suggest that HLHS has a complex genetic inheritance, its etiology remains largely unknown. The goal of this study was to characterize a risk gene in HLHS and its effect on HLHS etiology and outcome. We performed next-generation sequencing on a multigenerational family with a high prevalence of CHD/HLHS, identifying a rare variant in the α-myosin heavy chain (MYH6) gene. A case-control study of 190 unrelated HLHS subjects was then performed and compared with the 1000 Genomes Pro...
Source: Physiological Genomics - November 30, 2016 Category: Genetics & Stem Cells Authors: Tomita-Mitchell, A., Stamm, K. D., Mahnke, D. K., Kim, M.-S., Hidestrand, P. M., Liang, H. L., Goetsch, M. A., Hidestrand, M., Simpson, P., Pelech, A. N., Tweddell, J. S., Benson, D. W., Lough, J. W., Mitchell, M. E. Tags: Genomic and ' Polyomic Studies of Cardiovascular and Inflammatory Diseases Source Type: research
Transcriptomic differences in intra-abdominal adipose tissue in extremely obese adolescents with different stages of NAFLD
Mechanisms responsible for progression of nonalcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH) remain poorly defined. To examine the potential contribution of adipose tissue to NAFLD progression, we performed a complete transcriptomic analysis using RNA sequencing (RNA-Seq) on intra-abdominal adipose tissue (IAT) from severely obese adolescents [Mage 16.9 ± 0.4 yr, body mass index (BMI) z-score 2.7 ± 0.1] undergoing bariatric surgery and liver biopsy categorized into three groups: no steatosis (normal, n = 8), steatosis only (n = 13), or NASH (n = 10) by liver histology. Age, body weight, and BM...
Source: Physiological Genomics - November 30, 2016 Category: Genetics & Stem Cells Authors: Sheldon, R. D., Kanosky, K. M., Wells, K. D., Miles, L., Perfield, J. W., Xanthakos, S., Inge, T. H., Rector, R. S. Tags: General Interest Source Type: research
Reactive oxygen species and bacterial biofilms in diabetic wound healing
Chronic wounds are a common and debilitating complication for the diabetic population. It is challenging to study the development of chronic wounds in human patients; by the time it is clear that a wound is chronic, the early phases of wound healing have passed and can no longer be studied. Because of this limitation, mouse models have been employed to better understand the early phases of chronic wound formation. In the past few years, a series of reports have highlighted the importance of reactive oxygen species and bacterial biofilms in the development of chronic wounds in diabetics. We review these recent findings and ...
Source: Physiological Genomics - November 30, 2016 Category: Genetics & Stem Cells Authors: Nouvong, A., Ambrus, A. M., Zhang, E. R., Hultman, L., Coller, H. A. Tags: Physiological Genomics of Cell States and Their Regulation and Single Cell Genomics Source Type: research
Lifestyle and DNA base composition in polychaetes
A comparative analysis of polychaete species, classified as motile and low-motile forms, highlighted that the former were characterized not only by a higher metabolic rate (MR), but also by a higher genomic GC content. The fluctuation of both variables was not affected by the phylogenetic relationship of the species. Thus, present results further support that a very active lifestyle affects MR and GC at the same time, showing an unexpected similarity between invertebrates and vertebrates. In teleosts, indeed, a similar pattern has been also observed in comparisons of migratory and nonmigratory species. A cause-effect link ...
Source: Physiological Genomics - November 30, 2016 Category: Genetics & Stem Cells Authors: Tarallo, A., Gambi, M. C., D'Onofrio, G. Tags: Comparative, Statistical, and Computational Genomics and Model Organism Databases Source Type: research
Genome-wide association study of plasma resistin levels identified rs1423096 and rs10401670 as possible functional variants in the Japanese population
The objective was to identify additional functional variants for circulating resistin. We conducted a genome-wide association study in 448 Japanese subjects. A peak association signal was found on chromosome 19 where RETN is located. The top-hit SNP was SNP –358 G>A, followed by rs1423096 C>T, SNP –420 C>G, and rs10401670 C>T (P = 5.39x10–47, 1.81x10–22, 2.09x10–16, and 9.25x10–15, respectively). Meta-analysis including another two independent general Japanese populations showed that circulating resistin was most strongly associated with SNP-358, followed by SNP-420, rs142309...
Source: Physiological Genomics - November 13, 2016 Category: Genetics & Stem Cells Authors: Kawamura, R., Tabara, Y., Tsukada, A., Igase, M., Ohashi, J., Yamada, R., Takata, Y., Kawamoto, R., Saito, I., Onuma, H., Tanigawa, T., Yamada, K., Kato, N., Ohyagi, Y., Miki, T., Kohara, K., Osawa, H. Tags: Genome-wide Assocation Studies and Function Source Type: research
