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Physiological Genomics

Lesley A Graham, Alisha Aman, Desmond D Campbell, Julian Augley, Delyth Graham, Martin W McBride, Niall J Fraser, Nicholas R Ferreri, Anna F Dominiczak, Sandosh Padmanabhan
Previously, our comprehensive cardiovascular characterisation study validated Uromodulin as a blood pressure gene. Uromodulin is a glycoprotein exclusively synthesised at the thick ascending limb of the loop of Henle and is encoded by the Umod gene. Umod-/- mice have significantly lower blood pressure than Umod+/+ mice, are resistant to salt-induced changes in blood pressure, and show a leftward shift in pressure-natriuresis curves reflecting changes of sodium reabsorption. Salt stress triggers transcription factors and genes that alter renal sodium reabsorption...
September 14, 2018: Physiological Genomics
Qi Zhu, Renyuan Gao, Yi Zhang, Dengdeng Pan, Yefei Zhu, Xiaohui Zhang, Rong Yang, Rong Jiang, Yawei Xu, Huanlong Qin
BACKGROUND: Gut microbiota dysbiosis has been considered to be an important risk factor that contributes to coronary artery disease, but limited evidence is known about the involvement of gut microbiota in the disease. Our study aimed to characterize the dysbiosis signatures of gut microbiota in coronary artery disease. METHODS: The gut microbiota represented in stool samples were collected from 70 patients with coronary artery disease and 90 healthy controls. 16S rRNA sequencing was applied and bioinformatics methods were used to decipher taxon signatures and function alteration, as well as the microbial network and diagnostic model of gut microbiota in coronary artery disease...
September 7, 2018: Physiological Genomics
Scott A Booth, Glenn D Wadley, Francine Z Marques, Mary E Wlodek, Fadi J Charchar
BACKGROUND AND AIMS: Fetal and postnatal growth restriction predispose to cardiovascular disease (CVD) in adulthood. Telomeres are repetitive DNA-protein structures that protect chromosome ends, and the loss of these repeats (a reduction in telomere length) is associated with CVD. As exercise preserves telomere length and cardiovascular health, the aim of this study was to determine the effects of growth restriction and exercise training on cardiac telomere length and telomeric genes...
September 7, 2018: Physiological Genomics
Madhurima Saha, Hemakumar M Reddy, Mustafa Salih, Elicia Estrella, Michael D Jones, Satomi Mitsuhashi, Kyung-Ah Cho, Silveli Suzuki-Hatano, Skylar A Rizzo, Muddathir H Hamad, Maowia M Mukhtar, Ahlam A Hamed, Maha A Elseed, Monkol Lek, Elise Valkanas, Daniel G MacArthur, Louis M Kunkel, Christina A Pacak, Isabelle Draper, Peter B Kang
Next generation sequencing is commonly used to screen for pathogenic mutations in families with Mendelian disorders, but due to the pace of discoveries, gaps have widened for some diseases between genetic and pathophysiological knowledge. We recruited and analyzed 16 families with limb-girdle muscular dystrophy (LGMD) of Arab descent from Saudi Arabia and Sudan who did not have confirmed genetic diagnoses. The analysis included both traditional and next generation sequencing approaches. Cellular and metabolic studies were performed on Pyroxd1 siRNA C2C12 myoblasts and controls...
August 31, 2018: Physiological Genomics
Swathi Balaji, Xiaoyu Dong, Hui Li, Yuhao Zhang, Emily Steen, Krithika Lingappan
Bronchopulmonary dysplasia (BPD) is a chronic lung disease of the neonate characterized by impaired alveolarization and vascular growth. BPD is more common in premature male infants but the reasons underlying sexually dimorphic outcomes are not known. It is thought that alterations in fibroblast phenotype in response to environmental stress such as hyperoxia contributes to BPD. Notch signaling creates a pro-fibrotic environment in the lung. However, the role of hyperoxia on differential Notch pathway activation in male vs...
August 31, 2018: Physiological Genomics
Kailash N Pandey
Natriuretic peptides (NPs) exert diverse effects on several biological and physiological systems, such as kidney function, neural and endocrine signaling, energy metabolism, and cardiovascular function, playing pivotal roles in the regulation of blood pressure (BP) and cardiac and vascular homeostasis. NPs are collectively known as anti-hypertensive hormones and their main functions are directed towards eliciting natriuretic/diuretic, vasorelaxant, anti-proliferative, anti-inflammatory, and anti-hypertrophic effects, thereby, regulating the fluid volume, BP, and renal and cardiovascular conditions...
August 31, 2018: Physiological Genomics
Fatima Trebak, Wencheng Li, Yumei Feng
Increased sodium appetite is a physiological response to sodium deficiency; however, it has also been implicated in disease conditions such as congestive heart failure, kidney failure, and salt-sensitive hypertension. The central nervous system is the major regulator of sodium appetite and intake behavior; however, the neural mechanisms underlying this behavior remain incompletely understood. Here, we investigated the involvement of the (pro)renin receptor (PRR), a component of the brain renin-angiotensin system, in the regulation of sodium intake using a neuron-specific PRR knockout (PRRKO) mouse model generated previously in our laboratory...
August 24, 2018: Physiological Genomics
Vanessa R Kay, Matthew T Ratsep, Lindsay S Cahill, Andrew F Hickman, Bruno Zavan, Margaret E Newport, Jacob Ellegood, Christine L Laliberte, James N Reynolds, Peter Carmeliet, Chandrakant Tayade, John G Sled, B Anne Croy
Preeclampsia, a hypertensive syndrome occurring in 3-5% of human pregnancies, has lifelong health consequences for the fetus. Cognitive ability throughout life is altered and adult stroke risk is increased in these offspring. One potential etiological factor for altered brain development is low concentrations of pro-angiogenic placental growth factor (PGF). Impaired PGF production may promote an anti-angiogenic fetal environment during neural and cerebrovascular development. We previously reported delayed vascularization of the hindbrain, altered retinal vascular organization and less connectivity in the circle of Willis in Pgf-/- mice...
August 17, 2018: Physiological Genomics
Sarah Galla, Saroj Chakraborty, Xi Cheng, Jiyoun Yeo, Blair Mell, Helen Zhang, Anna V Mathew, Matam Vijay-Kumar, Bina Joe
Gut microbiota are associated with a variety of complex polygenic diseases. The usage of broad-spectrum antibiotics by patients affected by such diseases, is an important environmental factor to consider, because antibiotics, which are widely prescribed to curb pathological bacterial infections, also indiscriminately eliminate gut commensal microbiota. However, the extent to which antibiotics reshape gut microbiota and per se contribute to these complex diseases is understudied. Because genetics play an important role in predisposing individuals to these modern diseases, we hypothesize that the extent to which antibiotics influence complex diseases depends on host genome and metagenome...
August 10, 2018: Physiological Genomics
Theresa Casey, Joseph Walker, Ketaki P Bhide, Jyothi Thimmapuram, Jon Schoonmaker
Steer progeny suckled by cows fed a dried distillers grains and solubles (DDGS) diet the first three months of lactation were heavier during feedlot finishing and had significantly lower marbling and larger longissimus muscles than steer suckled by cows fed a control diet (CON). These differences were profound in that progeny were managed and fed identically from weaning until finishing, and findings suggested that the suckling period established the developmental program of muscle composition. Here transcriptomes of longissimus muscle were measured using next generation sequencing to investigate whether there were any developmental clues to the differences in marbling scores and muscle content between steers suckled by DDGS (n=5) versus control (CON; n=5) diet fed cows during lactation...
August 3, 2018: Physiological Genomics
Jin Xue, Dan Zhou, Orit Poulsen, Iain Hartley, Toshihiro Imamura, Edward X Xie, Gabriel G Haddad
Numerous studies have demonstrated that Na+ /H+ exchanger isoform 1 (NHE1) is elevated in myocardial diseases and its effect is detrimental. To better understand the involvement of NHE1, we have previously studied cardiac-specific NHE1 transgenic mice and shown that these mice develop cardiac hypertrophy, interstitial fibrosis and cardiac dysfunction. The purpose of current study was to identify microRNAs and their mRNA targets involved in NHE1-mediated cardiac injury. An un-biased high throughput sequencing study was performed on both microRNAs and mRNAs...
July 20, 2018: Physiological Genomics
Grant C O'Connell, Kyle B Walsh, Emily Burrage, Opeolu Adeoye, Paul D Chantler, Taura L Barr
Increasing evidence suggests that there are innate differences between sexes with respect to stroke pathophysiology, however the molecular mechanisms underlying these differences remain unclear. In this investigation, we employed a shotgun approach to broadly profile sex-associated differences in the plasma proteomes of a small group of male (n=6) and female (n=4) ischemic stroke patients. Peripheral blood was sampled during the acute phase of care, and liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) was used to quantify plasma proteins...
July 20, 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
Anastacia M Garcia, Ayed Allawzi, Philip Tatman, Laura Hernandez-Lagunas, Kalin Swain, Gary Mouradian, Russell 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 single nucleotide polymorphism (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 with wild-type (WT) littermates...
September 1, 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 vs...
September 1, 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, and 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...
September 1, 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...
September 1, 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 4,884 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...
September 1, 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 posttranslational 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...
September 1, 2018: Physiological Genomics
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