Strain survey and genetic analysis of vasoreactivity in mouse aorta
This study represents the first step toward the unbiased comprehensive discovery of genetic determinants that regulate intrinsic vascular function, particularly endothelial function. (Source: Physiological Genomics)
Source: Physiological Genomics - November 13, 2016 Category: Genetics & Stem Cells Authors: Kim, S. K., Avila, J. J., Massett, M. P. Tags: General Interest Source Type: research
Muscle dysfunction in a zebrafish model of Duchenne muscular dystrophy
Sapje zebrafish lack the protein dystrophin and are the smallest vertebrate model of Duchenne muscular dystrophy (DMD). Their small size makes them ideal for large-scale drug discovery screens. However, the extent that sapje mimic the muscle dysfunction of higher vertebrate models of DMD is unclear. We used an optical birefringence assay to differentiate affected dystrophic sapje larvae from their unaffected siblings and then studied trunk muscle contractility at 4–7 days postfertilization. Preparation cross-sectional area (CSA) was similar for affected and unaffected larvae, yet tetanic forces of affected preparatio...
Source: Physiological Genomics - November 13, 2016 Category: Genetics & Stem Cells Authors: Widrick, J. J., Alexander, M. S., Sanchez, B., Gibbs, D. E., Kawahara, G., Beggs, A. H., Kunkel, L. M. Tags: Comparative, Statistical, and Computational Genomics and Model Organism Databases Source Type: research
Peptide affinity analysis of proteins that bind to an unstructured region containing the transactivating domain of the osmoprotective transcription factor NFAT5
NFAT5 is a transcription factor originally identified because it is activated by hypertonicity and that activation increases expression of genes that protect against the adverse effects of the hypertonicity. However, its targets also include genes not obviously related to tonicity. The transactivating domain of NFAT5 is contained in its COOH-terminal region, which is predicted to be unstructured. Unstructured regions are common in transcription factors particularly in transactivating domains where they can bind co-regulatory proteins essential to their function. To identify potential binding partners of NFAT5 from either c...
Source: Physiological Genomics - November 13, 2016 Category: Genetics & Stem Cells Authors: Dumond, J. F., Zhang, X., Izumi, Y., Ramkissoon, K., Wang, G., Gucek, M., Wang, X., Burg, M. B., Ferraris, J. D. Tags: Call for Papers Source Type: research
Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41
In this study, our aims were to identify the cellular localization of Gpr41 and to determine its role in BP regulation. We localized Gpr41 to the vascular endothelium using RT-PCR: Gpr41 is detected in intact vessels (with endothelium) but is absent from denuded vessels (without endothelium). Furthermore, using pressure myography we confirmed that SCFAs dilate resistance vessels in an endothelium-dependent manner. Since we previously found that Gpr41 mediates a hypotensive response to acute SCFA administration, we hypothesized that Gpr41 knockout (KO) mice would be hypertensive. Here, we report that Gpr41 KO mice have isol...
Source: Physiological Genomics - November 13, 2016 Category: Genetics & Stem Cells Authors: Natarajan, N., Hori, D., Flavahan, S., Steppan, J., Flavahan, N. A., Berkowitz, D. E., Pluznick, J. L. Tags: Call for Papers Source Type: research
Selection-, age-, and exercise-dependence of skeletal muscle gene expression patterns in a rat model of metabolic fitness
Intrinsic aerobic exercise capacity can influence many complex traits including obesity and aging. To study this connection we established two rat lines by divergent selection of untrained aerobic capacity. After 32 generations the high capacity runners (HCR) and low capacity runners (LCR) differed in endurance running distance and body fat, blood glucose, other health indicators, and natural life span. To understand the interplay among genetic differences, chronological age, and acute exercise we performed microarray-based gene expression analyses in skeletal muscle with a 2x2x2 design to simultaneously compare HCR and LC...
Source: Physiological Genomics - October 31, 2016 Category: Genetics & Stem Cells Authors: Ren, Y.-y., Koch, L. G., Britton, S. L., Qi, N. R., Treutelaar, M. K., Burant, C. F., Li, J. Z. Tags: Call for Papers Source Type: research
Association of ADAMTS7 gene polymorphism with cardiovascular survival in coronary artery disease
Recent genetic studies have revealed an association between polymorphisms at the ADAMTS7 gene locus and coronary artery disease (CAD) risk. Functional studies have shown that a CAD-associated polymorphism (rs3825807) affects ADAMTS7 maturation and vascular smooth muscular cell (VSMC) migration. Here, we tested whether ADAMTS7 (A/G) SNP is associated with cardiovascular (CV) survival in patients with established CAD. A cohort of 1,128 patients with angiographic proven CAD, who were followed up prospectively for a mean follow-up period of 63 (range 6–182) mo, were genotyped for rs3825807 A/G. Survival statistics (Cox r...
Source: Physiological Genomics - October 31, 2016 Category: Genetics & Stem Cells Authors: Pereira, A., Palma dos Reis, R., Rodrigues, R., Sousa, A. C., Gomes, S., Borges, S., Ornelas, I., Freitas, A. I., Guerra, G., Henriques, E., Rodrigues, M., Freitas, S., Freitas, C., Brehm, A., Pereira, D., Mendonca, M. I. Tags: Call for Papers Source Type: research
Effects of dietary forage and calf starter on ruminal pH and transcriptomic adaptation of the rumen epithelium in Holstein calves during the weaning transition
We investigated the relationship between ruminal pH and transcriptomic adaptation of the rumen epithelium (RE) of calves fed calf starter with and without forage during the weaning transition. Holstein calves were assigned to groups fed calf starter either with forage (HAY group, n = 3) or without forage (CON group, n = 4). Ruminal pH was measured continuously, and rumen fluid and epithelium were collected 3 wk after weaning. mRNA expression profiles of the RE were examined by one-color microarray. Differentially expressed genes (DEGs) were investigated using the Ingenuity Pathway Analysis (IPA). Mean and maximum ruminal p...
Source: Physiological Genomics - October 31, 2016 Category: Genetics & Stem Cells Authors: Kim, Y.-H., Toji, N., Kizaki, K., Kushibiki, S., Ichijo, T., Sato, S. Tags: Call for Papers Source Type: research
Immune and inflammatory responses to freediving calculated from leukocyte gene expression profiles
Freedivers hold their breath while diving, causing blood oxygen levels to decrease (hypoxia) while carbon dioxide increases (hypercapnia). Whereas blood gas changes are presumably involved in the progression of respiratory diseases, less is known about their effect on healthy individuals. Here we have used gene expression profiling to analyze elite athletes' immune and inflammatory responses to freediving. Blood was collected before and 1 and 3 h after a series of maximal dynamic and static freediving apneas in a pool, and peripheral blood gene expression was mapped on genome-wide microarrays. Fractions of phenotypically d...
Source: Physiological Genomics - October 31, 2016 Category: Genetics & Stem Cells Authors: Eftedal, I., Flatberg, A., Drvis, I., Dujic, Z. Tags: Systems Biology of Exercise Source Type: research
Transcriptome assessment of the Pompe (Gaa-/-) mouse spinal cord indicates widespread neuropathology
Pompe disease, caused by deficiency of acid alpha-glucosidase (GAA), leads to widespread glycogen accumulation and profound neuromuscular impairments. There has been controversy, however, regarding the role of central nervous system pathology in Pompe motor dysfunction. We hypothesized that absence of GAA protein causes progressive activation of neuropathological signaling, including pathways associated with cell death. To test this hypothesis, genomic data (Affymetrix Mouse Gene Array 2.0ST) from the midcervical spinal cord in 6 and 16 mo old Pompe (Gaa–/–) mice were evaluated (Broad Institute Molecular Signat...
Source: Physiological Genomics - October 31, 2016 Category: Genetics & Stem Cells Authors: Turner, S. M. F., Falk, D. J., Byrne, B. J., Fuller, D. D. Tags: Physiological and Genetic Control of Neural Function Source Type: research
Comparative transcriptomic analysis identifies genes differentially expressed in human epicardial progenitors and hiPSC-derived cardiac progenitors
Regenerative therapies hold great potential to change the treatment paradigm for cardiac diseases. Human cardiac progenitor cells can be used for drug discovery in this area and also provide a renewable source of cardiomyocytes. However, a better understanding of their characteristics is critical for interpreting data obtained from drug screening using these cells. In the present study, we performed global transcriptional analysis of two important sources of cardiac progenitors, i.e., patient epicardium-derived cells (EPDCs) and cardiac progenitor cells (CPCs) derived from human induced pluripotent stem cells. In addition,...
Source: Physiological Genomics - October 31, 2016 Category: Genetics & Stem Cells Authors: Synnergren, J., Drowley, L., Plowright, A. T., Brolen, G., Goumans, M.-J., Gittenberger-de Groot, A. C., Sartipy, P., Wang, Q.-D. Tags: General Interest Source Type: research
A synthetic luciferin improves in vivo bioluminescence imaging of gene expression in cardiovascular brain regions
Bioluminescence imaging is an effective tool for in vivo investigation of molecular processes. We have demonstrated the applicability of bioluminescence imaging to spatiotemporally monitor gene expression in cardioregulatory brain nuclei during the development of cardiovascular disease, via incorporation of firefly luciferase into living animals, combined with exogenous d-luciferin substrate administration. Nevertheless, d-luciferin uptake into the brain tissue is low, which decreases the sensitivity of bioluminescence detection, particularly when considering small changes in gene expression in tiny central areas. Here, we...
Source: Physiological Genomics - October 12, 2016 Category: Genetics & Stem Cells Authors: Simonyan, H., Hurr, C., Young, C. N. Tags: Physiological and Genetic Control of Neural Function Source Type: research
RNA expression profile of calcified bicuspid, tricuspid, and normal human aortic valves by RNA sequencing
The objective of this study was to identify genes differentially expressed between calcified bicuspid aortic valves (BAVc) and tricuspid valves with (TAVc) and without (TAVn) AS using RNA sequencing (RNA-Seq). We collected 10 human BAVc and nine TAVc from men who underwent primary aortic valve replacement. Eight TAVn were obtained from men who underwent heart transplantation. mRNA levels were measured by RNA-Seq and compared between valve groups. Two genes were upregulated, and none were downregulated in BAVc compared with TAVc, suggesting a similar gene expression response to AS in individuals with bicuspid and tricuspid ...
Source: Physiological Genomics - October 2, 2016 Category: Genetics & Stem Cells Authors: Guauque-Olarte, S., Droit, A., Tremblay-Marchand, J., Gaudreault, N., Kalavrouziotis, D., Dagenais, F., Seidman, J. G., Body, S. C., Pibarot, P., Mathieu, P., Bosse, Y. Tags: General Interest Source Type: research
Differential roles of caveolin-1 in ouabain-induced Na+/K+-ATPase cardiac signaling and contractility
Binding of ouabain to cardiac Na+/K+-ATPase initiates cell signaling and causes contractility in cardiomyocytes. It is widely accepted that caveolins, structural proteins of caveolae, have been implicated in signal transduction. It is known that caveolae play a role in Na+/K+-ATPase functions. Regulation of caveolin-1 in ouabain-mediated cardiac signaling and contractility has never been reported. The aim of this study is to compare ouabain-induced cardiac signaling and contractility in wild-type (WT) and caveolin-1 knockout (cav-1 KO) mice. In contrast with WT cardiomyocytes, ouabain-induced signaling e.g., activation of ...
Source: Physiological Genomics - September 30, 2016 Category: Genetics & Stem Cells Authors: Bai, Y., Wu, J., Li, D., Morgan, E. E., Liu, J., Zhao, X., Walsh, A., Saikumar, J., Tinkel, J., Joe, B., Gupta, R., Liu, L. Tags: Genomic and ' Polyomic Studies of Cardiovascular and Inflammatory Diseases Source Type: research
The role of the hypothalamic-pituitary-adrenal axis in modulating seasonal changes in immunity
Seasonal changes in environmental conditions are accompanied by significant adjustment of multiple biological processes. In temperate regions, the day fraction, or photoperiod, is a robust environmental cue that synchronizes seasonal variations in neuroendocrine and metabolic function. In this work, we propose a semimechanistic mathematical model that considers the influence of seasonal photoperiod changes as well as cellular and molecular adaptations to investigate the seasonality of immune function. Our model predicts that the circadian rhythms of cortisol, our proinflammatory mediator, and its receptor exhibit seasonal ...
Source: Physiological Genomics - September 30, 2016 Category: Genetics & Stem Cells Authors: Pierre, K., Schlesinger, N., Androulakis, I. P. Tags: Comparative, Statistical, and Computational Genomics and Model Organism Databases Source Type: research
Serum response factor induces endothelial-mesenchymal transition in glomerular endothelial cells to aggravate proteinuria in diabetic nephropathy
We investigated the expression and function of serum response factor (SRF) in endothelial-mesenchymal transition (EndMT) in glomerular endothelial cells (GEnCs) of diabetic nephropathy (DN). The expression of SRF, endothelial markers (VE-cadherin, CD31), and mesenchymal markers (α-SMA, FSP-1, fibronectin) was examined in GEnCs following high glucose or in renal cortex tissues of DN rats. SRF was upregulated by SRF plasmids and downregulated by CCG-1423 (a small molecule inhibitor of SRF) to investigate how SRF influenced EndMT in GEnCs of DN. Streptozocin (STZ) was used to generate diabetes mellitus DM in rats. In GE...
Source: Physiological Genomics - September 30, 2016 Category: Genetics & Stem Cells Authors: Zhao, L., Zhao, J., Wang, X., Chen, Z., Peng, K., Lu, X., Meng, L., Liu, G., Guan, G., Wang, F. Tags: Genetic and Genomics Investigation of Structure and Function of the Kidney Source Type: research
