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Physiological Genomics

Saskia Reibe, Marit Hjorth, Mark A Febbraio, Martin Whitham
Exercise stimulates a wide array of biological processes, but the mechanisms involved are incompletely understood. Many previous studies have adopted transcriptomic analyses of skeletal muscle to address particular research questions, a process that ultimately results in the collection of large amounts of publicly available data that has not been fully integrated or interrogated. To maximize the use of these available transcriptomic exercise data sets, we have downloaded and re-analyzed them and formulated the data into a searchable online tool, geneXX...
March 16, 2018: Physiological Genomics
Timothy J Stodola, Pengyuan Liu, Yong Liu, Andrew Vallejos, Aron M Geurts, Andrew S Greene, Mingyu Liang
A challenge to understanding enhancer-gene relationships is that enhancers are not always sequentially close to the gene they regulate. Physical proximity mapping through sequencing can provide an unbiased view of the chromatin close to the proximal promoter of the renin gene (Ren). Our objective was to determine genomic regions that physically interact with the renin proximal promoter, using two different genetic backgrounds, the Dahl salt sensitive and normotensive SS-13BN, which have been shown to have different regulation of plasma renin in vivo...
March 9, 2018: Physiological Genomics
Colin A Nurse, Erin M Leonard, Shaima Salman
Mammalian carotid bodies (CB) are chemosensory organs that mediate compensatory cardiorespiratory reflexes in response to low blood PO2 (hypoxemia) and elevated CO2 /H+ (acid hypercapnia). The chemoreceptors are glomus or type I cells which occur in clusters enveloped by neighboring glial-like type II cells. During chemoexcitation type I cells depolarize, leading to Ca2+ -dependent release of several neurotransmitters, some excitatory and others inhibitory, which help shape the afferent carotid sinus nerve (CSN) discharge...
March 9, 2018: Physiological Genomics
Søren Brandt Poulsen, Kavee Limbutara, Robert Andrew Fenton, Trairak Pisitkun, Birgitte M Christensen
The renal aldosterone-sensitive distal tubule (ASDT) is crucial for sodium reabsorption and blood pressure regulation. The ASDT consists of the late distal convoluted tubule (DCT2), connecting tubule (CNT) and collecting duct. Due to difficulties in isolating epithelial cells from the ASDT in large quantities, few transcriptome studies have been performed on this segment. Moreover, no studies exist on isolated DCT2 and CNT cells (excluding intercalated cells), and the role of aldosterone for regulating the transcriptome of these specific cell types is largely unknown...
March 9, 2018: Physiological Genomics
Matthew R Panasevich, Umesh D Wankhade, Sree V Chintapalli, Kartik Shankar, R Scott Rector
BACKGROUND: The gut microbiome plays a critical role in the onset and progression of obesity and the metabolic syndrome. However, it is not well documented whether the cecal versus the fecal microbiome is more relevant when assessing its contribution to these diseases. Here, we amplified the V4 region of the 16S rRNA gene from cecal and fecal samples of female Ossabaw swine fed a low fat control diet (10.5% fat; n=4) or Western diet (43.0% fat; 17.8% high fructose corn syrup; 2% cholesterol; n=3) for 36 weeks...
March 9, 2018: Physiological Genomics
Dorien Reijnders, Chin-Chi Liu, Xinjing Xu, Anna Zhao, Kelsey Olson, Scott D Butler, Nataki C Douglas, Jenny L Sones
Preeclampsia (PE), a hypertensive disease of pregnancy, is a leading cause of fetal and maternal morbidity/mortality. Early angiogenic and inflammatory disturbances within the placenta are thought to underlie the development of the maternal PE syndrome and poor pregnancy outcomes. However, the exact etiology remains largely unknown. Here, we use the BPH/5 mouse model of PE to elucidate the way in which inflammation early in pregnancy contributes to abnormal expression of angiogenic factors at the maternal-fetal interface...
March 9, 2018: Physiological Genomics
Charu Rajput, Megan P Walsh, Breanna N Eder, Ediri E Metitiri, Antonia P Popova, Marc B Hershenson
Infections with rhinovirus (RV) cause asthma exacerbations. Recent studies suggest that macrophages play a role in asthmatic airway inflammation and the innate immune response to RV infection. Macrophages exhibit discrete phenotypes based on surface markers and gene expression. We hypothesized that macrophage polarization state alters gene expression in response to RV infection. Cells were derived from human peripheral blood derived monocytes. M1 and M2 polarization was carried out using IFN-y and IL-4, respectively, and RNA was extracted for Affymetrix Human Gene ST2...
March 9, 2018: Physiological Genomics
Shengdi Li, Ziyi Chang, Tianqing Zhu, Yixue Li, Bruce A Freeman, Y Eugene Chen, Jifeng Zhang
Nitro-conjugated linoleic acid (NO2 -CLA) is formed by metabolic and inflammatory reactions of nitric oxide and nitrite, and represents the most abundant nitro-fatty acid species in humans. These electrophilic fatty acid nitroalkene derivatives mediate pleiotropic cell signaling responses. Here, we report a systematic approach to investigate the effect of NO2 -CLA on human coronary artery smooth muscle cells (hCASMC), based on the RNA-seq and bioinformatics analysis. There were extensive differentially expressed genes in NO2 -CLA vs...
February 23, 2018: Physiological Genomics
Nabeel Abdulrahman, Béatrice Jaspard Vinassa, Larry Fliegel, Ayesha Jabeen, Sadaf Riaz, Alain-Pierre Gadeau, Fatima Mraiche
Cardiovascular diseases are the leading cause of death worldwide. One in three cases of heart failure is due to dilated cardiomyopathy. The Na+ /H+ exchanger isoform 1 (NHE1), a multifunctional protein and the key pH regulator in the heart, has been demonstrated to be increased in this condition. We have previously demonstrated that elevated NHE1 activity induced cardiac hypertrophy in vivo. Furthermore, the overexpression of active NHE1 elicited modulation of gene expression in cardiomyocytes including an upregulation of myocardial osteopontin (OPN) expression...
February 23, 2018: Physiological Genomics
Ying Wang, Xiaoxi Huang, Dong Leng, Jifeng Li, Lei Wang, Yan Liang, Jun Wang, Ran Miao, Tao Jiang
Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening disease which is often underpinned by vascular remodeling. Although pulmonary arterial smooth muscle cells (PASMCs) are the main participants in vascular remodeling, their biological role in CTEPH is not entirely clear. In this study, we analyzed the whole epigenome-wide DNA methylation profiles of cultured PASMCs from CTEPH and control cell lines using an Illumina HumanMethylation450K BeadChip. A total of 6829 significantly differentially methylated probes (DMPs) were detected between the two groups, of which 4246 DMPs were hypermethylated while 2583 DMPs were hypomethylated...
February 23, 2018: Physiological Genomics
Ruifang Li-Gao, Salma Majid Wakil, Brian F Meyer, Nduna Dzimiri, Dennis O Mook-Kanamori
Over 120 type 2 diabetes (T2D) loci have been identified from genome-wide association analysis (GWAS), mainly from Caucasian populations. Very limited knowledge is available on the Saudi Arabian population. In this study, 122 previously reported T2D related variants from 84 loci were examined in a Saudi Arabian cohort of 1,578 individuals (659 T2D cases and 919 controls). Eleven SNPs corresponding to 9 independent loci had a p-value <0.05. If a more stringent Bonferroni threshold of p=4.1×10 -4 (=0.05/122) was applied, none of the SNPs would have reached the significance level...
February 16, 2018: Physiological Genomics
Na Jiao, Susan S Baker, Colleen A Nugent, Maria Tsompana, Liting Cai, Yong Wang, Michael J Buck, Robert J Genco, Robert D Baker, Ruixin Zhu, Lixin Zhu
BACKGROUND: A number of studies have associated obesity with altered gut microbiota, although results are discordant regarding compositional changes in the gut microbiota of obese animals. Herein we aimed to obtain an unbiased evaluation of structural and functional changes of the gut microbiota in diet-induced obese rodents using a meta-analysis. METHODS: The raw sequencing data of nine studies generated with high-fat diet (HFD)-induced obese rodent models were processed with QIIME to obtain gut microbiota compositions...
January 26, 2018: Physiological Genomics
Anna Marie Williams, Yong Liu, Kevin R Regner, Fabrice Jotterand, Pengyuan Liu, Mingyu Liang
Big data is a major driver in the development of precision medicine. Efficient analysis methods are needed to transform big data into clinically-actionable knowledge. To accomplish this, many researchers are turning towards machine learning (ML), an approach of artificial intelligence (AI) that utilizes modern algorithms to give computers the ability to learn. Much of the effort to advance ML for precision medicine has been focused on the development and implementation of algorithms and the generation of ever larger quantities of genomic sequence data and electronic health records...
January 26, 2018: Physiological Genomics
Silvia V Conde, Joana F Sacramento, Maria P Guarino
The carotid body is currently looked at as a multipurpose sensor for blood gases, blood pH and several hormones. The matter of glucose sensing by the carotid body has been debated for several years in the literature, and nowadays there is a consensus that carotid body activity is modified by metabolic factors that contribute to glucose homeostasis. However, the sensing ability for glucose is still being pondered: are the carotid bodies low glucose sensors or, in contrast, are they overresponsive in high-glucose conditions? Herein, we debate the glucose and insulin sensing capabilities of the carotid body as the key early events in the overactivation of the carotid body that result in insulin resistance culminating in the development of metabolic diseases...
January 26, 2018: Physiological Genomics
Ruifang Li-Gao, Renée de Mutsert, Frits R Rosendaal, Ko Willems van Dijk, Dennis O Mook-Kanamori
In 2015, a genome-wide association study described 59 independent signals that showed strong associations with 85 fasting metabolite concentrations as measured by the Biocrates AbsoluteIDQTM p150 kit. However, the human body resides in a non-fasting state for the greater part of the day and the genetic basis of postprandial metabolite concentrations remains largely unknown. We systematically examined these previously identified genetic associations in postprandial metabolite concentrations after a mixed meal...
January 26, 2018: Physiological Genomics
James Shull, Kirsten Dennison, Aaron Chack, Amy Trentham-Dietz
Numerous laboratory and epidemiologic studies strongly implicate endogenous and exogenous estrogens in the etiology of breast cancer. Data summarized herein suggest that the ACI rat model of 17β-estradiol (E2)-induced mammary cancer is unsurpassed among rodent models in the extent to which it faithfully reflects the etiology and biology of luminal types of breast cancer, which together constitute approximately 70% of all breast cancers. E2 drives cancer development in this model through mechanisms that are largely dependent upon estrogen receptors and require progesterone and its receptors...
January 26, 2018: Physiological Genomics
Makiko Onishi, Ko Yamanaka, Yasunori Miyamoto, Hidefumi Waki, Sabine S Gouraud
Arterial pressure (AP) is lower in pre-menopausal women than in men of a similar age. Pre-menopausal women exhibit a lower sympathetic outflow and a greater baroreceptor reflex; however, mechanisms for the gender differences in blood pressure regulation are still not well understood. We hypothesized that different neuronal functions in the cardiovascular centers in the brains of men and women could contribute to the gender difference in cardiovascular homeostasis. Our previous studies on male spontaneously hypertensive rats (SHRs) and their normotensive counterparts, Wistar Kyoto (WKY) rats, revealed that the gene expression profile of the nucleus tractus solitarius (NTS), a pivotal region of the medulla oblongata for regulating the set-point of AP, is strongly associated with the AP level...
January 26, 2018: Physiological Genomics
Xin Gao, Maria S Oei, Catherine E Ovitt, Murat Sincan, James E Melvin
RNA-seq was used to better understand the molecular nature of the biological differences among the three major exocrine salivary glands in mammals. Transcriptional profiling found that the adult murine parotid, submandibular and sublingual salivary glands express greater than 14,300 protein-coding genes, and nearly 2,000 of these genes were differentially expressed. Principle component analysis of the differentially expressed genes revealed three distinct clusters according to gland type. The three salivary gland transcriptomes were dominated by a relatively few number of highly expressed genes (6...
January 26, 2018: Physiological Genomics
Yi Li, Qiang Feng, Miao Guo, Yuding Wang, Yunliang Jiang, Jinyi Xing
Folic acid supplements during pregnancy can prevent neural tube defects and other developmental abnormalities. Here, we explored the effects of folate supplement on gene expression and DNA methylation during C2C12 differentiation. Based on the folic acid concentration, this study comprised three groups: low folate (L), normal folate (N), and high-folate supplement (H). Our analyses revealed that differentiation and the mRNA expression of myogenin in C2C12 cell were enhanced by folic acid, however, the overall methylation percentage in myogenin promoter between different treatment groups was not significantly different (P>0...
January 12, 2018: Physiological Genomics
Katherine Chen, Alice Jih, Olivia Osborn, Sarah T Kavaler, Wenxian Fu, Roman Sasik, Rintaro Saito, Jane J Kim
Highly inbred C57BL/6 mice show wide variation in their degree of insulin resistance in response to diet-induced obesity even though they are almost genetically identical. Here we employed transcriptional profiling by RNA sequencing (RNA-Seq) of visceral adipose tissue (VAT) and liver in young mice to determine how gene expression patterns correlate with the later development of high-fat diet (HFD)-induced insulin resistance in adulthood. To accomplish this goal, we partially removed and banked tissues from pubertal mice...
January 8, 2018: Physiological Genomics
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