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Physiological Genomics

Anastacia M Garcia, Ayed Allawzi, Philip Tatman, Laura Hernandez-Lagunas, Kalin Swain, Gary Mouradian, Russell P Bowler, Anis Karimpour-Fard, Carmen C Sucharov, Eva Nozik-Grayck
Extracellular Superoxide Dismutase (EC-SOD), one of three mammalian SOD isoforms, is the sole extracellular enzymatic defense against superoxide. A known human SNP in the matrix-binding domain of EC-SOD characterized by an arginine to glycine substitution at position 213 (R213G), redistributes EC-SOD from the matrix into extracellular fluids. We previously reported that knock-in mice harboring the human R213G SNP (R213G mice) exhibited enhanced resolution of inflammation with subsequent protection against fibrosis following bleomycin treatment compared to wild-type (WT) littermates...
July 13, 2018: Physiological Genomics
Xingrao Ke, Hollis Johnson, Xigang Jing, Teresa Michalkiewicz, Yi-Wen Huang, Robert H Lane, Girija G Konduri
Decreased expression of endothelial nitric oxide synthase (eNOS), a key mediator of perinatal transition, characterizes persistent pulmonary hypertension of the newborn (PPHN) in neonates and a fetal lamb model; the mechanisms are unclear. We investigated whether increased DNA CpG methylation at the eNOS promoter in estrogen response elements (EREs) and altered histone code together contribute to decreased eNOS expression in PPHN. We isolated pulmonary artery endothelial cells (PAEC) from fetal lambs with PPHN induced by prenatal ductus arteriosus constriction from 128-136 days gestation or gestation matched twin controls...
July 13, 2018: Physiological Genomics
Emily S Riddle, Erica L Bender, Anna Thalacker-Mercer
Primary human muscle progenitor cells (hMPCs) are commonly used to understand skeletal muscle biology, including the regenerative process. Variability from unknown origin in hMPC expansion capacity occurs independent of disease, age, or sex of the donor. We sought to determine the transcript profile that distinguishes hMPC cultures with greater expansion capacity and to identify biological underpinnings of these transcriptome profile differences. Sorted (CD56+/CD29+) hMPC cultures were clustered using unbiased K means cluster analysis into FAST and SLOW based on growth parameters (saturation density and population doubling time)...
July 13, 2018: Physiological Genomics
Sreekumar Othumpangat, Donald H Beezhold, John D Noti
Host-viral interaction occurring throughout the infection process between the influenza A virus (IAV) and bronchial cells determines the success of infection. Our previous studies showed that the apoptotic pathway triggered by the host cells was repressed by IAV facilitating prolonged survival of infected cells. A detailed understanding on the role of IAV in altering the cell death pathway during early stage infection of human bronchial epithelial cells (HBEpCs) is still unclear. We investigated the gene expression profiles of IAV-infected versus mock-infected cells at the early stage of infection using a PCR array for death receptor (DR) pathway...
June 29, 2018: Physiological Genomics
Yoshitake Cho, Robert S Ross
Immobilization, bed rest, or denervation leads to muscle disuse and subsequent skeletal muscle atrophy. Muscle atrophy can also occur as a component of various chronic diseases such as cancer, AIDS, sepsis, diabetes, chronic heart failure, or as a direct result of genetic muscle disorders. In addition to this atrophic loss of muscle mass, metabolic deregulation of muscle also occurs. In contrast, physical exercise plays a beneficial role in counteracting disuse-induced atrophy by increasing muscle mass and strength...
June 29, 2018: Physiological Genomics
Janet L Fitzakerley, George J Trachte
Although hearing loss is the most common sensory deficit in western societies, there are no successful pharmacological treatments for this disorder. Recent experiments have demonstrated that manipulation of intracellular cyclic guanosine monophosphate (cGMP) concentrations can have both beneficial and harmful effects on hearing. In this review, we will examine the role of cGMP as a key second messenger involved in many aspects of cochlear function, and discuss the known functions of downstream effectors of cGMP in sound processing...
June 29, 2018: Physiological Genomics
Yoshiki Yasukochi, Jun Sakuma, Ichiro Takeuchi, Kimihiko Kato, Mitsutoshi Oguri, Tetsuo Fujimaki, Hideki Horibe, Yoshiji Yamada
Recent genome-wide association studies have identified various genetic variants associated with hematological traits. Although it is possible that quantitative data of hematological traits are varied among the years examined, conventional genome-wide association studies have been conducted in a cross-sectional manner that measures traits at a single point in time. To address this issue, we have traced blood profiles in 4884 Japanese individuals who underwent annual health check-ups for several years. In the present study, longitudinal exome-wide association studies were conducted to identify genetic variants related to 13 hematological phenotypes...
June 29, 2018: Physiological Genomics
Kelly A Hyndman, Chin-Rang Yang, Hyun Jun Jung, Ezigbobiara N Umejiego, Chung-Ling Chou, Mark A Knepper
Phosphorylation and lysine (K)-acetylation are dynamic post-translational modifications of proteins. Previous proteomic studies have identified over 170,000 phosphorylation sites, and 15,000 K-acetylation sites in mammals. We recently reported that the inner medullary collecting duct (IMCD), which functions in the regulation of water-reabsorption, via the actions of vasopressin, expresses many of the enzymes that can modulated K-acetylation. The purpose of this study was to determine the K-acetylated or phosphorylated proteins expressed in IMCD cells...
June 22, 2018: Physiological Genomics
Ehab Billatos, Alen Faiz, Yaron O Gesthalter, Ashley LeClerc, Yuriy Alekseyev, Xiaohui Zhang, Gang Liu, Nick H T Ten Hacken, Irene Heijink, Wim Timens, Corry-Anke Brandsma, Dirkje S Postma, Maarten van den Berge, Avrum Spira, Marc E Lenburg
BACKGROUND: Understanding effects of Acute Smoke Exposure (ASE) on airway epithelial gene expression and their relationship with the effects of Chronic Smoke Exposure (CSE) may provide biological insights into the development of smoking-related respiratory diseases. METHODS: Bronchial airway epithelial cell brushings were collected from 63 individuals without recent cigarette smoke exposure, before and 24-hours after smoking three cigarettes. RNA from these samples was profiled on Affymetrix Human Gene 1...
June 22, 2018: Physiological Genomics
Xiaoling Zhang, Alissa A Frame, Jonathan S Williams, Richard D Wainford
Salt sensitivity of blood pressure (BP) increases hypertension risk and associated adverse cardiovascular outcomes. At present, there are no validated rapid tests or diagnostic markers to identify salt sensitivity of BP in clinical practice. Based on our prior animal studies that report a role for brain Gαi2 proteins in the salt sensitivity of BP and evidence that GNAI2 (single-nucleotide polymorphism) SNPs associate with hypertension risk, we investigated the hypothesis that GNAI2 SNPs associate with salt sensitivity of BP in humans...
June 15, 2018: Physiological Genomics
Henry Reyer, Michael Oster, Elizabeth Magowan, Eduard Murani, Helga Sauerwein, Dirk Dannenberger, Björn Kuhla, Siriluck Ponsuksili, Klaus Wimmers
Feed efficiency (FE) is a measure of the rate between feed intake and body weight gain and is subject to constant progress in pigs, based on extensive performance tests and analyses of physiological parameters. However, endocrine regulatory circuits which comprise the sensation and perception of intrinsic requirements and appropriate systemic responses have not yet been fully elucidated. It is hypothesized that the gut-brain-axis, which is a network of hierarchical anterior regulatory tissues, contributes largely to variations in FE...
June 15, 2018: Physiological Genomics
Steven D Hicks, Paige Jacob, Frank A Middleton, Omar Perez, Zofia Gagnon
Micro-ribonucleic acids (miRNAs) mediate adaptive responses to exercise and may serve as biomarkers of exercise intensity/capacity. Expression of miRNAs is altered in skeletal muscle, plasma, and saliva following exertion. Females display unique physiologic responses to endurance exercise, and miRNAs respond to pathologic states in sex-specific patterns. However sex-specific miRNA responses to exercise remain unexplored. This study utilized high-throughput RNA sequencing to measure changes in salivary RNA expression among 25 collegiate runners following a single long-distance run...
June 8, 2018: Physiological Genomics
Alyson A Fiorillo, Christopher B Tully, Jesse M Damsker, Kanneboyina Nagaraju, Eric P Hoffman, Christopher R Heier
Corticosteroids are highly prescribed and effective anti-inflammatory drugs, but the burden of side effects with chronic use significantly detracts from patient quality of life, particularly in children. Developing safer steroids amenable to long-term use is an important goal for treatment of chronic inflammatory diseases such as Duchenne muscular dystrophy (DMD). We have developed vamorolone (VBP15), a first-in-class dissociative glucocorticoid receptor (GR) ligand that shows the anti-inflammatory efficacy of corticosteroids without key steroid side effects in animal models...
June 8, 2018: Physiological Genomics
Philipp Baumert, Claire E Stewart, Mark J Lake, Barry Drust, Robert M Erskine
We investigated whether single nucleotide polymorphisms (SNPs) within genes encoding the alpha-1 chain of type I (COL1A1, rs2249492; rs1800012), type II (COL2A1, rs2070739) and type V (COL5A1, rs12722) collagen were associated with the variable response to exercise-induced muscle damage (EIMD). Knee extensor muscle strength and soreness were assessed pre-, post-, and 48h post-EIMD (120 maximal eccentric knee extensor contractions) in 65 young healthy participants, who were genotyped for the aforementioned SNPs...
May 25, 2018: Physiological Genomics
Alessandra Adami, Brian D Hobbs, Merry-Lynn McDonald, Richard Casaburi, Harry B Rossiter
Muscle oxidative capacity is a major determinant of maximum oxygen uptake (V̇O2max ). V̇O2max predicts survival in humans. Muscle oxidative capacity is low in chronic obstructive pulmonary disease (COPD), and can be assessed from the muscle oxygen consumption recovery rate constant ( k) using near-infrared spectroscopy. We hypothesized that 11 SNPs previously associated with the increase in V̇O2max following exercise training, would correlate with k in 152 non-Hispanic White and African American smokers with and without COPD...
May 25, 2018: Physiological Genomics
Yujia Yang, Qiang Fu, Xiaozhu Wang, Yang Liu, Qifan Zeng, Yun Li, Sen Gao, Lisui Bao, Shikai Liu, Dongya Gao, Rex Dunham, Zhanjiang Liu
Channel catfish is the leading aquaculture species in the US, and one of the reasons for its application in aquaculture is its relatively high tolerance against hypoxia. However, hypoxia can still cause huge economic losses to the catfish industry. Studies on hypoxia tolerance, therefore, are important for aquaculture. Fish swimbladder has been considered as an accessory respiration organ surrounded by a dense capillary countercurrent exchange system. In this regard, we conducted RNA-Seq analysis with swimbladder samples of catfish under hypoxic and normal conditions to determine if swimbladder was responsive to low oxygen treatment, and to reveal genes, their expression patterns and pathways involved in hypoxia responses in catfish...
May 25, 2018: Physiological Genomics
Anselm A Derda, Chin Cheng Woo, Thidathip Wongsurawat, Mark Richards, Chuen Neng Lee, Theo Kofidis, Vladimir A Kuznetsov, Vitaly A Sorokin
Myocardial infarction (MI) induced by acute coronary arterial occlusion is usually secondary to atherosclerotic plaque rupture. Dysregulated response of vascular smooth muscle cells (VSMCs) in atherosclerotic plaques may promote plaque rupture. Cadherins (CDHs) form adherens junctions and are known stabilizers of atherosclerotic plaques. To date, the expression patterns of cadherin have not been well investigated in MI aortic VSMCs. We aimed to investigate the expression of cadherin genes in the aortic wall of patients with and without MI...
May 18, 2018: Physiological Genomics
Xiaolong Zhou, Songbai Yang, Feifei Yan, Ke He, Ayong Zhao
DNA methylation is an important epigenetic modification involved in the estrous cycle and the regulation of reproduction. Here, we investigated the genome-wide profiles of DNA methylation in porcine proestrus and estrus ovaries using methylated DNA immunoprecipitation sequencing (MeDIP-seq). The results showed that DNA methylation was enriched in intergenic and intron regions. The methylation levels of coding regions were higher than those of the 5' and 3' flanking regions of genes. There were 4813 differentially methylated regions (DMRs) of CpG islands in the estrus vs...
May 18, 2018: Physiological Genomics
Priscilla R Prestes, Francine Z Marques, Guillermo Lopez-Campos, Paul Lewandowski, Lea M D Delbridge, Fadi J Charchar, Stephen B Harrap
Hypertrophic cardiomyopathy thickens heart muscles reducing functionality and increasing risk of cardiac disease and morbidity. Genetic factors are involved, but their contribution is poorly understood. We used the hypertrophic heart rat (HHR), a unique normotensive polygenic model of cardiac hypertrophy and heart failure to investigate the role of genes associated with monogenic human cardiomyopathy. We selected 42 genes involved in monogenic human cardiomyopathies to study: 1) DNA variants, by sequencing the whole-genome of 13-week old HHR and age-matched normal heart rat (NHR), its genetic control strain; 2) mRNA expression, by targeted RNA-sequencing in left ventricles of HHR and NHR at five ages (2-days old, 4-, 13-, 33- and 50-weeks old) compared to human idiopathic dilated data; and 3) microRNA expression, with rat microRNA microarrays in left ventricles of 2-days old HHR and age-matched NHR...
May 18, 2018: Physiological Genomics
Sun Hyung Kwon, Li Li, Christi M Terry, Yan-Ting Shiu, Philip J Moos, Brett A Milash, Alfred K Cheung, Donald K Blumenthal
Arteriovenous hemodialysis graft (AVG) stenosis results in thrombosis and AVG failure, and develops chiefly as a consequence of localized neointimal hyperplasia (NH) formation in the vein-graft anastomosis region. The vein region just downstream of the vein-graft anastomosis (herein termed proximal vein region) is relatively resistant to NH. Prevention of AVG stenosis has been ineffective due in part to our limited understanding of the molecular processes involved in NH formation. We hypothesized that the gene expression profiles of the NH-prone and NH-resistant regions will be different from each other after graft placement, and analysis of their genomic profiles may yield therapeutic targets to prevent AVG stenosis...
May 11, 2018: Physiological Genomics
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