Transcriptome profiling reveals novel BMI- and sex-specific gene expression signatures for human cardiac hypertrophy
How obesity or sex may affect the gene expression profiles of human cardiac hypertrophy is unknown. We hypothesized that body-mass index (BMI) and sex can affect gene expression profiles of cardiac hypertrophy. Human heart tissues were grouped according to sex (male, female), BMI (lean<25 kg/m2, obese>30 kg/m2), or left ventricular hypertrophy (LVH) and non-LVH nonfailed controls (NF). We identified 24 differentially expressed (DE) genes comparing female with male samples. In obese subgroup, there were 236 DE genes comparing LVH with NF; in lean subgroup, there were seven DE genes comparing LVH with NF. In female sub...
Source: Physiological Genomics - July 7, 2017 Category: Genetics & Stem Cells Authors: Newman, M. S., Nguyen, T., Watson, M. J., Hull, R. W., Yu, H.-G. Tags: Research Articles Source Type: research
Advancing precision medicine in healthcare: addressing implementation challenges to increase pharmacogenetic testing in the clinical setting
The incorporation of precision medicine into the clinical setting is becoming increasingly feasible with the availability of more affordable genetic sequencing technologies and successful genetic associations with phenotypes, especially in the pharmacogenomic field. Although substantial progress has been made to ensure successful uptake of pharmacogenomic testing in the clinical setting already, many challenges still remain for sustainable implementation. The importance of pharmacogenomic information in patient care, identifying key barriers, and proposed solutions for advancing pharmacogenomic implementation will be discu...
Source: Physiological Genomics - July 7, 2017 Category: Genetics & Stem Cells Authors: Dong, O. M., Wiltshire, T. Tags: Perspectives Source Type: research
LINC00341 exerts an anti-inflammatory effect on endothelial cells by repressing VCAM1
The long noncoding RNAs (lncRNAs), which constitute a large portion of the transcriptome, have gained intense research interest because of their roles in regulating physiological and pathophysiological functions in the cell. We identified from RNA-Seq profiling a set of lncRNAs in cultured human umbilical vein endothelial cells (HUVECs) that are differentially regulated by atheroprotective vs. atheroprone shear flows. Among the comprehensively annotated lncRNAs, including both known and novel transcripts, LINC00341 is one of the most abundant lncRNAs in endothelial cells. Moreover, its expression level is enhanced by ather...
Source: Physiological Genomics - July 1, 2017 Category: Genetics & Stem Cells Authors: Huang, T.-S., Wang, K.-C., Quon, S., Nguyen, P., Chang, T.-Y., Chen, Z., Li, Y.-S., Subramaniam, S., Shyy, J., Chien, S. Tags: Research Articles Source Type: research
Transcriptional networks in rodent models support a role for gut-brain communication in neurogenic hypertension: a review of the evidence
Hypertension (HTN) is the most prevalent condition observed in primary health care. Hypertension shows complex etiology, and neuroinflammation, overactive sympathetic drive, and the microbiome are each associated with the disease. To obtain mechanistic perspective into neurogenic HTN, we first constructed a framework for transcriptional regulators of the disease using the Comparative Toxicogenomics Database. This approach yielded a core group of 178 transcripts that are prevalent in studies of HTN, including leptin and neuropeptide Y. We then conducted a meta-analysis for transcriptome data generated in brain tissue from H...
Source: Physiological Genomics - July 1, 2017 Category: Genetics & Stem Cells Authors: Zubcevic, J., Baker, A., Martyniuk, C. J. Tags: Review Source Type: research
Exercise-induced modification of the skeletal muscle transcriptome in Arabian horses
It has been found that Arabian and Thoroughbred horses differ in muscle fiber structure and thus in physiological changes occurring in muscles during exercise. The aim of the present study was to identify the global gene expression modifications that occur in skeletal muscle following a training regime to prepare for flat racing. Whole transcriptomes of muscle (gluteus medius) were compared between three time points of tissue collection: T0 (untrained horses), T1 (horses after intense gallop phase), and T2 (horses at the end of racing season), 23 samples in total. The numerous groups of exercise-regulated differentially ex...
Source: Physiological Genomics - June 23, 2017 Category: Genetics & Stem Cells Authors: Ropka-Molik, K., Stefaniuk-Szmukier, M., Zukowski, K., Piorkowska, K., Bugno-Poniewierska, M. Tags: Research Articles Source Type: research
Molecular structure and function of big calcium-activated potassium channels in skeletal muscle: pharmacological perspectives
The large-conductance Ca2+-activated K+ (BK) channel is broadly expressed in various mammalian cells and tissues such as neurons, skeletal muscles (sarco-BK), and smooth muscles. These channels are activated by changes in membrane electrical potential and by increases in the concentration of intracellular calcium ion (Ca2+). The BK channel is subjected to many mechanisms that add diversity to the BK channel α-subunit gene. These channels are indeed subject to alternative splicing, auxiliary subunits modulation, posttranslational modifications, and protein-protein interactions. BK channels can be modulated by diverse ...
Source: Physiological Genomics - June 8, 2017 Category: Genetics & Stem Cells Authors: Maqoud, F., Cetrone, M., Mele, A., Tricarico, D. Tags: Perspectives Source Type: research
De novo RNA sequence assembly during in vivo inflammatory stress reveals hundreds of unannotated lincRNAs in human blood CD14+ monocytes and in adipose tissue
Long intergenic noncoding RNAs (lincRNAs) have emerged as key regulators of cellular functions and physiology. Yet functional lincRNAs often have low, context-specific and tissue-specific expression. We hypothesized that many human monocyte and adipose lincRNAs would be absent in current public annotations due to lincRNA tissue specificity, modest sequencing depth in public data, limitations of transcriptome assembly algorithms, and lack of dynamic physiological contexts. Deep RNA sequencing (RNA-Seq) was performed in peripheral blood CD14+ monocytes (monocytes; average ~247 million reads per sample) and adipose tissue (av...
Source: Physiological Genomics - June 1, 2017 Category: Genetics & Stem Cells Authors: Xue, C., Zhang, X., Zhang, H., Ferguson, J. F., Wang, Y., Hinkle, C. C., Li, M., Reilly, M. P. Tags: Research Articles Source Type: research
Gene expression effects of glucocorticoid and mineralocorticoid receptor agonists and antagonists on normal human skeletal muscle
Mineralocorticoid and glucocorticoid receptors are closely related steroid hormone receptors that regulate gene expression through many of the same hormone response elements. However, their transcriptional activities and effects in skeletal muscles are largely unknown. We recently identified mineralocorticoid receptors (MR) in skeletal muscles after finding that combined treatment with the angiotensin-converting enzyme inhibitor lisinopril and MR antagonist spironolactone was therapeutic in Duchenne muscular dystrophy mouse models. The glucocorticoid receptor (GR) agonist prednisolone is the current standard-of-care treatm...
Source: Physiological Genomics - June 1, 2017 Category: Genetics & Stem Cells Authors: Chadwick, J. A., Hauck, J. S., Gomez-Sanchez, C. E., Gomez-Sanchez, E. P., Rafael-Fortney, J. A. Tags: Research Articles Source Type: research
Role of renal transporters and novel regulatory interactions in the TAL that control blood pressure
Hypertension (HTN), a major public health issue is currently the leading factor in the global burden of disease, where associated complications account for 9.4 million deaths worldwide every year. Excessive dietary salt intake is among the environmental factors that contribute to HTN, known as salt sensitivity. The heterogeneity of salt sensitivity and the multiple mechanisms that link high salt intake to increases in blood pressure are of upmost importance for therapeutic application. A continual increase in the kidney’s reabsorption of sodium (Na+) relies on sequential actions at various segments along the nephron....
Source: Physiological Genomics - May 18, 2017 Category: Genetics & Stem Cells Authors: Graham, L. A., Dominiczak, A. F., Ferreri, N. R. Tags: Review Source Type: research
Cancer cachexia-induced muscle atrophy: evidence for alterations in microRNAs important for muscle size
Muscle atrophy is a hallmark of cancer cachexia resulting in impaired function and quality of life and cachexia is the immediate cause of death for 20–40% of cancer patients. Multiple microRNAs (miRNAs) have been identified as being involved in muscle development and atrophy; however, less is known specifically on miRNAs in cancer cachexia. The purpose of this investigation was to examine the miRNA profile of skeletal muscle atrophy induced by cancer cachexia to uncover potential miRNAs involved with this catabolic condition. Phosphate-buffered saline (PBS) or Lewis lung carcinoma cells (LLC) were injected into C57BL...
Source: Physiological Genomics - May 1, 2017 Category: Genetics & Stem Cells Authors: Lee, D. E., Brown, J. L., Rosa-Caldwell, M. E., Blackwell, T. A., Perry, R. A., Brown, L. A., Khatri, B., Seo, D., Bottje, W. G., Washington, T. A., Wiggs, M. P., Kong, B.-W., Greene, N. P. Tags: Research Articles Source Type: research
MiR-146a/b: a family with shared seeds and different roots
MicroRNAs are small, noncoding, RNAs known for their powerful modulation of molecular processes, making them a major focus for studying pathological mechanisms. The human miR-146 family of microRNAs consists of two member genes, MIR146A and MIR146B. These two microRNAs are located on different chromosomes and exhibit differential regulation in many cases. However, they are nearly identical in sequence, sharing a seed region, and are thus predicted to target the same set of genes. A large proportion of the microRNA (miR)-146 literature focuses on its role in regulating the innate immune response in the context of various pa...
Source: Physiological Genomics - April 14, 2017 Category: Genetics & Stem Cells Authors: Paterson, M. R., Kriegel, A. J. Tags: Review Source Type: research
Short-term low-magnesium diet reduces autoimmune arthritis severity and synovial tissue gene expression
This study revealed a novel role for dietary magnesium in the regulation of autoimmune arthritis and opens new possibilities for the treatment of autoimmune diseases such as rheumatoid arthritis and psoriatic arthritis with short courses of dietary or drug-induced modulations of magnesium levels. (Source: Physiological Genomics)
Source: Physiological Genomics - April 1, 2017 Category: Genetics & Stem Cells Authors: Brenner, M., Laragione, T., Gulko, P. S. Tags: Research Articles Source Type: research
Blunted transcriptional response to skeletal muscle ischemia in rats with chronic kidney disease: potential role for impaired ischemia-induced angiogenesis
Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. Previous studies indicated an impairment of ischemia-induced angiogenesis in skeletal muscle of rats with CKD. We performed a systematic comparison of early gene expression in response to ischemia in rats with or without CKD to identify potential molecular mechanisms underlying impaired angiogenesis in CKD. CKD was induced in male rats by 5/6 nephrectomy (SNX); control rats were sham operated (sham). Eight weeks later, ischemia of the right limb was induced by ligation and resection of the femoral artery. Rats were killed 24 h...
Source: Physiological Genomics - April 1, 2017 Category: Genetics & Stem Cells Authors: Heiss, R. U., Fahlbusch, F. B., Jacobi, J., Daniel, C., Ekici, A. B., Cordasic, N., Amann, K., Hartner, A., Hilgers, K. F. Tags: Research Articles Source Type: research
Genetic analysis of 10 pedigrees with inherited retinal degeneration by exome sequencing and phenotype-genotype association
Our purpose was to identify causative mutations and characterize the phenotype associated with the genotype in 10 unrelated families with autosomal recessive retinal degeneration. Ophthalmic evaluation and DNA isolation were carried out in 10 pedigrees with inherited retinal degenerations (IRD). Exomes of probands from eight pedigrees were captured using Nimblegen V2/V3 or Agilent V5+UTR kits, and sequencing was performed on Illumina HiSeq. The DHDDS gene was screened for mutations in the remaining two pedigrees with Ashkenazi Jewish ancestry. Exome variants were filtered to detect candidate causal variants using exomeSuit...
Source: Physiological Genomics - April 1, 2017 Category: Genetics & Stem Cells Authors: Biswas, P., Duncan, J. L., Maranhao, B., Kozak, I., Branham, K., Gabriel, L., Lin, J. H., Barteselli, G., Navani, M., Suk, J., Parke, M., Schlechter, C., Weleber, R. G., Heckenlively, J. R., Dagnelie, G., Lee, P., Riazuddin, S. A., Ayyagari, R. Tags: Research Articles Source Type: research
Transcriptomic alterations in the brain of painted turtles (Chrysemys picta) developmentally exposed to bisphenol A or ethinyl estradiol
Developmental exposure of turtles and other reptiles to endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA) and ethinyl estradiol (EE), can stimulate partial to full gonadal sex-reversal in males. We have also recently shown that in ovo exposure to either EDC can induce similar sex-dependent behavioral changes typified by improved spatial learning and memory or possibly feminized brain responses. Observed behavioral changes are presumed to be due to BPA- and EE-induced brain transcriptomic alterations during development. To test this hypothesis, we treated painted turtles (Chrysemys picta) at developmental s...
Source: Physiological Genomics - April 1, 2017 Category: Genetics & Stem Cells Authors: Manshack, L. K., Conard, C. M., Bryan, S. J., Deem, S. L., Holliday, D. K., Bivens, N. J., Givan, S. A., Rosenfeld, C. S. Tags: Research Articles Source Type: research
