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Physiological Genomics

Alisha R Coffey, Matt Kanke, Tangi L Smallwood, Jody Albright, Wendy Pitman, Raad Z Gharaibeh, Kunjie Hua, Erik Gertz, Sudha B Biddinger, Ryan E Temel, Daniel Pomp, Praveen Sethupathy, Brian J Bennett
OBJECTIVE: Trimethylamine-N-oxide (TMAO), a microbial choline metabolism byproduct that is processed in the liver and excreted into circulation, is associated with increased atherosclerotic lesion formation and cardiovascular disease risk. Genetic regulators of TMAO levels are largely unknown. In the present study, we used ~300 mice from a genetically heterogeneous mouse population (Diversity Outbred; DO) to determine hepatic microRNA associations with TMAO in the context of an atherogenic diet...
January 11, 2019: Physiological Genomics
Diana Balasubramanian, John F Pearson, Martin A Kennedy
Valproic acid (VPA) and lithium are widely used in the treatment of bipolar disorder. However, the underlying mechanism of action of these drugs is not clearly understood. We used RNA-Seq analysis to examine the global profile of gene expression in a rat serotonergic cell line (RN46A) after exposure to these two mood stabilizer drugs. Numerous genes were differentially regulated in response to VPA (log2 fold change ≥ 1.0; i.e. odds ratio of ≥ 2, at FDR <5%), but only two genes ( Dynlrb2 and Cdyl2) showed significant differential regulation after exposure of the cells to lithium, with the same analysis criteria...
December 21, 2018: Physiological Genomics
Yun-Yan Lou, Qiong-Dan Wang, Yu-Tian Lu, Meng-Yun Tu, Xi Xu, Ying Xia, Ying Peng, Mei-Mei Lai, Xiao-Qun Zheng
Human cytomegalovirus (HCMV) is an opportunistic prototypic beta-herpesvirus that can cause severe and even fatal diseases in immune-naive newborns and immunocompromised adults. Host-virus interactions occurring at the transcriptional and post-transcriptional levels are critical for establishing an HCMV latent or lytic infection, but the mechanisms remain poorly understood. Herein, we investigated the expression of circRNAs in human leukemia monocytes (THP-1 cells) latently infected with HCMV and explored the diagnostic value of circRNAs in children with HCMV infection...
December 21, 2018: Physiological Genomics
Hara Levy, Shuang Jia, Amy Pan, Xi Zhang, Mary L Kaldunski, Melodee L Nugent, Melissa Reske, Rachel A Feliciano, Diana Quintero, Michael M Renda, Katherine J Woods, Kathy Murkowski, Keven Johnson, James Verbsky, Trivikram Dasu, Justin Eze Ideozu, Susanna McColley, Michael W Quasney, Mary K Dahmer, Ellis D Avner, Philip M Farrell, Carolyn L Cannon, Howard Jacob, Pippa M Simpson, Martin J Hessner
Although cystic fibrosis (CF) is attributed to dysfunction of a single gene, the relationships between the abnormal gene product and development of inflammation and progression of lung disease are not fully understood, limiting our ability to predict an individual patient's clinical course and treatment response. To better understand CF progression, we characterized the molecular signatures of CF disease status using plasma-based functional genomics. Peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured with plasma samples from CF patients (n=103) and unrelated, healthy controls (n=31)...
December 12, 2018: Physiological Genomics
Maarten Caspers, Sara Blocquiaux, Ruben Charlier, Johan Lefevre, Katrien De Bock, Martine Thomis
Metabolic syndrome (MetS) is a highly prevalent condition causing increased risk of several life-threatening diseases. MetS has a pronounced hereditary basis, but is also influenced by environmental factors, partly through epigenetic mechanisms. In this study, the five phenotypes underlying MetS were incorporated into a continuous score for metabolic fitness (MF) and associations with both genotypic variation and leukocyte DNA methylation were investigated. Baseline MF phenotypes (waist circumference, blood pressure, blood glucose, serum triglycerides and high-density lipoproteins) of 710 healthy Flemish adults were measured...
December 7, 2018: Physiological Genomics
Eric A Kirk, Shiva M Singh, Charles L Rice
The ATP2A2 gene encodes the SERCA protein required for active calcium re-uptake to the sarcoplasmic reticulum in cardiac and slow-twitch skeletal muscle. The ATP2A2 rs3026468 variant has been associated with voluntary strength phenotypes in humans but requires further validation. Here we investigated a homogenous cohort of eighty, young, healthy, active Caucasian males who were assessed for maximal isometric strength, voluntary activation, stimulated contractile properties and potentiation in the quadriceps...
December 7, 2018: Physiological Genomics
Jiffin Kuriacko Paulose, Charles Vincent Cassone, Vincent M Cassone
The gastrointestinal (GI) system is vital in its capacities for nutrient and water uptake, immune function, metabolism and detoxification, and stem-cell derived regeneration. Of significance to human health are a myriad of gastrointestinal disorders associated with aging that integrate with the circadian clock. Here we present data from three groups of mice: young (3 months old), middle-aged (12 months old), and old-aged (24 months old). Small intestine and colon samples taken every 4 hours under light:dark (LD) conditions were assayed for gene expression related to molecular circadian rhythmicity, transcription, cell-signaling, and immune function...
November 16, 2018: Physiological Genomics
Adrienne A Cheng, Laura L Hernandez, Wenli Li
Maternal consumption of a high fat diet (HFD) during pregnancy has established adverse effects on the developing neonate. In this study, we aimedto investigate the effect of a HFD on the murine mammary gland during mid-lactation. Female C57BL/6J mice were placed on either a low-fat diet (LFD/10% fat) or HFD (60% fat) from three weeks of age through peak lactation (lactation day 11/L11). After four weeks of consuming either the LFD or HFD, female mice were bred. There were no significant differences in milk yield between treatment groups, which was measured from L1-L9...
October 19, 2018: Physiological Genomics
Madhurima Saha, Hemakumar M Reddy, Mustafa A 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...
November 1, 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 contribute to BPD. Notch signaling creates a profibrotic environment in the lung. However, the role of hyperoxia on differential Notch pathway activation in male vs...
November 1, 2018: Physiological Genomics
Marius Catalin Staiculescu, Austin Cocciolone, Jesse Procknow, Jungsil Kim, Jessica E Wagenseil
Elastic fibers provide reversible elasticity to the large arteries and are assembled during development when hemodynamic forces are increasing. Mutations in elastic fiber genes are associated with cardiovascular disease. Mice lacking expression of the elastic fiber genes elastin (Eln-/- ), fibulin-4 (Efemp2-/- ), or lysyl oxidase (Lox-/- ) die at birth with severe cardiovascular malformations. All three genetic knockout models have elastic fiber defects, aortic wall thickening, and arterial tortuosity. However, Eln-/- mice develop arterial stenoses, while Efemp2-/- and Lox-/- mice develop ascending aortic aneurysms...
October 12, 2018: Physiological Genomics
Thomas A Blackwell, Igor Cervenka, Bhuwan Khatri, Jacob L Brown, Megan E Rosa-Caldwell, David E Lee, Richard A Perry, Lemuel A Brown, Wesley S Haynie, Michael P Wiggs, Walter G Bottje, Tyrone A Washington, Byungwhi Caleb Kong, Jorge L Ruas, Nicholas P Greene
Cancer-Cachexia (CC) is a wasting condition directly responsible for 20-40% of cancer-related deaths. The mechanisms controlling development of CC-induced muscle wasting are not fully elucidated. Most investigations focus on the post-cachectic state and do not examine progression of the condition. We recently demonstrated mitochondrial degenerations precede muscle wasting in time course progression of CC. However, the extent of muscle perturbations prior to wasting in CC is unknown. Therefore, we performed global gene expression analysis in CC-induced muscle wasting to enhance understanding of intramuscular perturbations across the development of CC...
October 5, 2018: Physiological Genomics
Pingxian Wu, Kai Wang, Qiang Yang, Jie Zhou, Dejuan Chen, Jideng Ma, Qianzi Tang, Long Jin, Weihang Xiao, Anan Jiang, Yanzhi Jiang, Li Zhu, Mingzhou Li, Xuewei Li, Guoqing Tang
Total number born(TNB),number born alive(NBA)and litter weight born alive(LWB)are critically important traits in pig production.The sow's parity is one of the major factors influencing litter traits.Because of monogenic or polygenic contributions and the presence of temporal gene effects in different sows' parities,it is difficult to clarify the biological and genetic background.To systematically explore the genetic mechanism of litter traits,18 GWASs were conducted using single-step GWAS(ssGWAS) based on two breeds(908 Landrace and 1130 Large White sow litter records)for each litter trait in different parities...
October 5, 2018: Physiological Genomics
Stephanie J Valberg, Sudeep Perumbakkam, Erica C McKenzie, Carrie J Finno
Equine myofibrillar myopathy (MFM) causes exertional muscle pain and is characterized by myofibrillar disarray and ectopic desmin aggregates of unknown origin. To investigate the pathophysiology of MFM, we compared resting and 3 h post-exercise transcriptomes of gluteal muscle and the resting skeletal muscle proteome of MFM and control Arabian horses using RNA-sequencing and iTRAQ analyses. Three hours after exercise, 191 genes were identified as differentially expressed (DE) in MFM vs. control muscle with &gt; 1 log2 fold change [FC] in genes involved in sulfur compound/ cysteine metabolism such as cystathionine-beta-synthase [CBS, ↓4...
October 5, 2018: Physiological Genomics
Qi Zhu, Renyuan Gao, Yi Zhang, Dengdeng Pan, Yefei Zhu, Xiaohui Zhang, Rong Yang, Rong Jiang, Yawei Xu, Huanlong Qin
Gut microbiota dysbiosis has been considered to be an important risk factor that contributes to coronary artery disease (CAD), but limited evidence exists about the involvement of gut microbiota in the disease. Our study aimed to characterize the dysbiosis signatures of gut microbiota in coronary artery disease. The gut microbiota represented in stool samples were collected from 70 patients with coronary artery disease and 98 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...
October 1, 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 in a neuron-specific PRR knockout (PRRKO) mouse model generated previously in our laboratory...
October 1, 2018: Physiological Genomics
Vanessa R Kay, Matthew T Rätsep, 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 fetuses. Cognitive ability throughout life is altered, and adult stroke risk is increased. One potential etiological factor for altered brain development is low concentrations of proangiogenic placental growth factor (PGF). Impaired PGF production may promote an antiangiogenic 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...
October 1, 2018: Physiological Genomics
S Galla, S Chakraborty, X Cheng, J Yeo, B Mell, H Zhang, A V Mathew, M Vijay-Kumar, B 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 the host genome and metagenome...
October 1, 2018: Physiological Genomics
T M Casey, J F Walker, K Bhide, J Thimmapuram, J P Schoonmaker
Steer progeny suckled by cows fed a dried distillers grains and solubles (DDGS) diet the first 3 mo of lactation were heavier during feedlot finishing and had significantly lower marbling and larger longissimus muscles than steers 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 suggest that the suckling period established the developmental program of muscle composition. Here transcriptomes of longissimus muscle were measured by 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) vs...
October 1, 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 unbiased high-throughput sequencing study was performed on both microRNAs and mRNAs...
October 1, 2018: Physiological Genomics
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