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Physiological Genomics

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https://www.readbyqxmd.com/read/29212850/endothelial-transcriptomics-reveals-activation-of-fibrosis-related-pathways-in-hypertension
#1
Jonathan William Nelson, Mohammed Zubaerul Ferdaus, James A McCormick, Jessica Minnier, Sanjiv Kaul, David H Ellison, Anthony Paul Barnes
Hypertension poses a significant challenge to vasculature homeostasis and stands as the most common cardiovascular disease in the world. Its effects are especially profound on endothelial cells that form the inner lining of the vasculature and are directly exposed to the effects of excess pressure. Here, we characterize the in vivo transcriptomic response of cardiac endothelial cells to hypertension by rapidly isolating these cells from the spontaneous hypertension mouse model BPH/2J and its normotensive BPN/3J control strain and performing and RNA sequencing on both...
December 6, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29212849/trim63-murf-1-gene-polymorphism-is-associated-with-biomarkers-of-exercise-induced-muscle-damage
#2
Philipp Baumert, Mark J Lake, Barry Drust, Claire Stewart, Robert M Erskine
Unaccustomed strenuous exercise can lead to muscle strength loss, inflammation and delayed onset muscle soreness, which may be influenced by genetic variation. We investigated if a missense single nucleotide polymorphism (A>G, rs2275950) within the TRIM63 gene (encoding MuRF-1 and potentially affecting titin mechanical properties) was associated with the variable response to unaccustomed eccentric exercise. Sixty-five untrained, healthy participants (genotyped for rs2275950: AA, AG and GG) performed 120 maximal eccentric knee extensions (ECC) to induce muscle damage...
December 6, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29212848/association-of-complement-receptor-1-gene-polymorphisms-with-cognitive-function
#3
Laurien Ermine Zijlstra, J Wouter Jukema, Simon P Mooijaart, Marijke A de Vries, David J Stott, Manuel Castro Cabezas, Stella Trompet
Previous evidence suggest involvement of the complement receptor 1 (CR1) in development of Alzheimer's disease. We investigated the association of CR1 gene polymorphisms with cognitive function in older subjects. Single nucleotide polymorphisms (SNPs) within the CR1 region on chromosome 1 (n=73) were assessed in 5244 participants in the PROspective Study of Pravastatin in the Elderly at Risk (51.9% female, mean age75.3 years). Linear regression, adjusted for age, sex, country and use of pravastatin, was used to assess the association between the SNPs and cognitive function, All 73 SNPs within the genomic region of the CR1 gene on chromosome 1 were extracted...
December 6, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29212847/attempted-replication-of-snps-in-rankl-and-opg-with-musculoskeletal-adverse-events-during-aromatase-inhibitor-treatment-for-breast-cancer
#4
Jacqueline M Dempsey, Jingyue Xi, N Lynn Henry, James M Rae, Daniel L Hertz
Aromatase inhibitor (AI) therapy is highly efficacious in the treatment of estrogen receptor-positive breast cancer, however in a subset of patients AI use is discontinued due to drug-induced musculoskeletal adverse events (MS-AE). Several studies have investigated the role of germline single nucleotide polymorphisms on patients' risk of MS-AE's, however no associations have yet to be validated for translation into clinical practice. This study attempted to replicate SNPs in RANKL (rs7984870) and OPG (rs2073618) on the risk of AI-induced MS-AEs, and screen for secondary associations with MS-AE related treatment discontinuation and serum and urine markers of bone health...
December 6, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29212846/associations-of-del-301-303-alpha2b-adrenoceptor-gene-polymorphism-with-central-hemodynamic-parameters-in-the-northern-russian-population
#5
Vladimir N Melnikov, Victor Baranov, Irina Suvorova, Sergey Krivoschekov
The ADRA2B gene 301-303 I/D polymorphism is associated with various cardiovascular phenotypes. However, an association of genotypes with the timing structure of cardiac cycle remains unclear. The central hemodynamic parameters were assessed by pulse wave analysis in 63 healthy residents of Kola Peninsula (68 N) aged 27-65 years. The genotypes were determined by PCR. The multiple regression analysis adjusted for age, BMI, heart rate, and blood pressure revealed that II genotype carriers had higher values of augmentation index, ejection duration and lower SEVR than DD homozygotes...
December 6, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29187515/nrf2-at-the-heart-of-oxidative-stress-and-cardiac-protection
#6
Qin M Chen, Anthony J Maltagliati
The NFE2L2 gene encodes the transcription factor Nrf2 best known for regulating the expression of antioxidant and detoxification genes. Gene knockout approaches have demonstrated its universal cytoprotective features. While Nrf2 has been the topic of intensive research in cancer biology since its discovery in 1994, understanding the role of Nrf2 in cardiovascular disease has just begun. The literature concerning Nrf2 in experimental models of atherosclerosis, ischemia, reperfusion, cardiac hypertrophy, heart failure, and diabetes supports its cardiac protective character...
November 29, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29167198/comparative-transcriptome-analysis-reveals-conserved-branching-morphogenesis-related-genes-involved-in-chamber-formation-of-catfish-swimbladder
#7
Yujia Yang, Qiang Fu, Yang Liu, Xiaozhu Wang, Rex Dunham, Shikai Liu, Lisui Bao, Qifan Zeng, Tao Zhou, Ning Li, Zhenkui Qin, Chen Jiang, Dongya Gao, Zhanjiang Liu
The swimbladder is an internal gas-filled organ in teleosts. Its major function is to regulate buoyancy. Swimbladder exhibits great variations in size, shape, number of compartments or chambers among teleosts. However, the genomic control of swimbladder variations is unknown. Channel catfish (Ictalurus punctatus), blue catfish (Ictalurus furcatus), and their F1 hybrids of female channel catfish x male blue catfish (C×B hybrid catfish) provide a good model to investigate the swimbladder morphology, because channel catfish possess a single-chambered swimbladder whereas blue catfish possess a bi-chambered swimbladder; and C×B hybrid catfish possess a bi-chambered swimbladder but with significantly reduced posterior chamber...
November 22, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29127223/systems-genetic-analysis-of-brown-adipose-tissue-function
#8
Michal Pravenec, Laura Saba, Vaclav Zidek, Vladimir Landa, Petr Mlejnek, Jan Silhavy, Miroslava Simakova, Hynak Strnad, Jaroslava Trnovska, Vojtech Skop, Martina Huttl, Irena Markova, Olena Oliyarnyk, Hana Malinska, Ludmila Kazdova, Harry Smith, Boris Tabakoff
Brown adipose tissue (BAT) has been suggested to play an important role in lipid and glucose metabolism in rodents and possibly also in humans. In the current study, we used genetic and correlation analyses in the BXH/HXB recombinant inbred (RI) strains, derived from Brown Norway (BN) and spontaneously hypertensive rats (SHR), to identify genetic determinants of BAT function. Linkage analyses revealed a quantitative trait locus (QTL) associated with interscapular BAT mass on chromosome 4 and two closely linked QTLs associated with glucose oxidation and glucose incorporation into BAT lipids on chromosome 2...
November 10, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29127222/mef2-transcription-factors-in-human-placenta-and-involvement-in-cytotrophoblast-invasion-and-differentiation
#9
Lucy Li, Lewis P Rubin, Xiaoming Gong
Development of the human placenta and its trophoblast cell types is critical for successful pregnancy. Defects in trophoblast invasion and differentiation are associated with adverse pregnancy outcomes, including preeclampsia. The members of myocyte enhancer factor-2 (MEF2) family of transcription factors are key regulators of cellular proliferation, differentiation, and invasion in various cell types and tissues and might play a similarly important role in regulating trophoblast proliferation, invasion, and differentiation during human placental development...
November 10, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29127221/genetics-of-metabolic-syndrome-potential-clues-from-wild-derived-inbred-mouse-strains
#10
Subashini Karunakaran, Susanne Michelle Clee
The metabolic syndrome (MetS) is a complex constellation of metabolic abnormalities including obesity, abnormal glucose metabolism, dyslipidemia, and elevated blood pressure that together substantially increase risk for cardiovascular disease and type 2 diabetes. Both genetic and environmental factors contribute to the development of MetS, but this process is still far from understood. Human studies have revealed only part of the underlying basis. Studies in mice offer many strengths that can complement human studies to help elucidate the etiology and pathophysiology of MetS...
November 10, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29127220/therapeutic-potential-of-micrornas-for-the-treatment-of-renal-fibrosis-and-ckd
#11
Wenshan Lv, Fan Fan, Yangang Wang, Ezekiel Gonzalez-Fernandez, Chen Wang, Lili Yang, George W Booz, Richard J Roman
Chronic kidney disease (CKD), defined as reduced glomerular filtration rate, is increasingly becoming a major public health issue. At the histological level, renal fibrosis is the final common pathway leading to end-stage renal disease, irrespective of the initial injury. According to this view, antifibrotic agents should slow or halt the progression of CKD. However, due to multiple overlapping pathways stimulating fibrosis, it has been difficult to develop antifibrotic drugs that delay or reverse the progression of CKD...
November 10, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29093195/the-effect-of-high-fat-diet-on-secreted-milk-transcriptome-in-mid-lactation-mice
#12
Yulu Chen, Junhui Wang, Shiqi Yang, Sagar Utturkar, Jennifer Crodian, Shelby Cummings, Jyothi Thimmapuram, Phillip San Miguel, Shihuan Kuang, Michael Gribskov, Karen Plaut, Theresa Casey
High fat diet (HFD) during lactation alters milk composition and is associated with development of metabolic diseases in the offspring. We hypothesized that HFD affects milk microRNA (miRNA) and mRNA content, which potentially impact offspring development. Our objective was to determine the effect of maternal HFD on secreted milk transcriptome. To meet this objective, 4-week old female ICR mice were divided into two treatment groups: control diet (CD) containing 10% kcal fat and HFD containing 60% kcal fat...
November 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29093194/distribution-and-function-of-the-muscarinic-receptor-subtypes-in-the-cardiovascular-system
#13
Hannah C Saternos, Daniyah A Almarghalani, Hayley M Gibson, Mahmood A Meqdad, Raymond B Antypas, Ajay Lingireddy, Wissam A AbouAlaiwi
Muscarinic acetylcholine receptors belong to the G-protein coupled receptor superfamily and are widely known to mediate numerous functions within the central and peripheral nervous system. Thus, they have become attractive therapeutic targets for various disorders. It has long been known that the parasympathetic system, governed by acetylcholine, plays an essential role in regulating cardiovascular function. Unfortunately, due to the lack of pharmacologic selectivity for any one muscarinic receptor, there was a minimal understanding of their distribution and function within this region...
November 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28916633/systems-genetics-identifies-a-co-regulated-module-of-liver-micrornas-associated-with-plasma-ldl-cholesterol-in-murine-diet-induced-dyslipidemia
#14
Alisha R Coffey, Tangi L Smallwood, Jody Albright, Kunjie Hua, Matt Kanke, Daniel Pomp, Brian J Bennett, Praveen Sethupathy
Chronically altered levels of circulating lipids, termed dyslipidemia, is a significant risk factor for a number of metabolic and cardiovascular morbidities. MicroRNAs (miRNAs) have emerged as important regulators of lipid balance, have been implicated in dyslipidemia, and have been proposed as candidate therapeutic targets in lipid-related disorders including atherosclerosis. A major limitation of most murine studies of miRNAs in lipid metabolic disorders is that they have been performed in just one (or very few) inbred strains, such as C57BL/6...
November 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28887369/genetic-mechanisms-of-human-hypertension-and-their-implications-for-blood-pressure-physiology
#15
REVIEW
Eric Seidel, Ute I Scholl
Hypertension, or elevated blood pressure, constitutes a major public health burden that affects more than 1 billion people worldwide and contributes to ~9 million deaths annually. Hereditary factors are thought to contribute to up to 50% of interindividual blood pressure variability. Blood pressure in the general population approximately shows a normal distribution and is thought to be a polygenic trait. In rare cases, early-onset hypertension or hypotension are inherited as Mendelian traits. The identification of the underlying Mendelian genes and variants has contributed to our understanding of the physiology of blood pressure regulation, emphasizing renal salt handling and the renin angiotensin aldosterone system as players in the determination of blood pressure...
November 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29030493/intrinsic-aerobic-capacity-governs-the-associations-between-gut-microbiota-composition-and-fat-metabolism-age-dependently-in-rat-siblings
#16
Satu Pekkala, Sanna Lensu, Miriam Nokia, Sanja Vanhatalo, Lauren G Koch, Steven L Britton, Heikki Kainulainen
Host genetic factors affecting the gut microbiome play an important role in obesity. Yet limited attention has been paid on the host genetic factors linked to physical fitness in modifying the microbiome. This study determined whether sibling-matched pairs of rats selectively bred for high (HCR) and low (LCR) aerobic capacity differ in their microbiome age-dependently and which taxa associate with differential in metabolism. Several taxa in young adult rats (hereafter young) linked to inherited aerobic capacity while in older adult (hereafter old) rats most of the differences between the lines associated with body weight...
October 13, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28986397/potential-mechanisms-of-hypothalamic-renin-angiotensin-system-activation-by-leptin-and-doca-salt-for-the-control-of-resting-metabolism
#17
Sarah A Sapouckey, Guorui Deng, Curt D Sigmund, Justin L Grobe
The renin-angiotensin system (RAS), originally described as a circulating hormone system, is an enzymatic cascade in which the final vasoactive peptide angiotensin II (ANG) regulates cardiovascular, hydromineral, and metabolic functions. The RAS is also synthesized locally in a number of tissues including the brain, where it can act in a paracrine fashion to regulate blood pressure, thirst, fluid balance, and resting energy expenditure / resting metabolic rate (RMR). Recent studies demonstrate that ANG AT1A receptors (Agtr1a) specifically in agouti-related peptide (AgRP) neurons of the arcuate nucleus (ARC) coordinate autonomic and energy expenditure responses to various stimuli including deoxycorticosterone acetate (DOCA)-salt, high fat feeding, and leptin...
October 6, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28986396/ace-modulated-adiposity-is-related-to-higher-energy-expenditure-and-independent-of-lipolysis-and-glucose-incorporation-into-lipids-in-adipocytes
#18
Miriam Helena Fonseca-Alaniz, Talita Sayuri Higa, Tarcila Beatriz Ferraz-de-Campos, Julie Takada, Francisco L Torres-Leal, Fabiana Sant'Anna Evangelista, Fabio B Lima, José Eduardo Krieger
Emerging evidence suggests that both systemic and white adipose tissue (WAT)-renin-angiotensin system components influence body weight control. We previously demonstrated that higher angiotensin-converting enzyme (ACE) gene expression is associated with lower body adiposity in a rodent model. In this study, we tested the hypothesis that a higher ACE gene dosage reduces fat accumulation by increasing energy expenditure and modulating lipolysis and glucose incorporation into lipids in adipocytes. After a 12-week follow-up period, transgenic mice harboring 3 ACE (3ACE) gene copies, displayed diminished WAT mass, lipid content in their carcasses, adipocyte hypotrophy, and higher resting oxygen uptake (VO2) in comparison with animals with 1 ACE gene copy (1ACE) after long fasting (12-hour)...
October 6, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28939642/dietary-fat-modulation-of-hepatic-lipase-variant-514-c-t-for-lipids-a-crossover-randomized-dietary-intervention-trial-in-caribbean-hispanics
#19
C E Smith, M I Van Rompay, J Mattei, J F Garcia, B Garcia-Bailo, A H Lichtenstein, K L Tucker, J M Ordovás
The hepatic lipase (LIPC) locus is a well-established determinant of high-density lipoprotein cholesterol (HDL-C) concentrations, an association that is modified by dietary fat in observational studies. Dietary interventions are lacking. We investigated dietary modulation of LIPC rs1800588 (-514 C/T) for lipids and glucose using a randomized crossover design comparing a high-fat Western diet and a low-fat traditional Hispanic diet in individuals of Caribbean Hispanic descent (n = 42, 4 wk/phase). No significant gene-diet interactions were observed for HDL-C...
October 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28887371/germline-genetic-variants-with-implications-for-disease-risk-and-therapeutic-outcomes
#20
REVIEW
Amy L Pasternak, Kristen M Ward, Jasmine A Luzum, Vicki L Ellingrod, Daniel L Hertz
Genetic testing has multiple clinical applications including disease risk assessment, diagnosis, and pharmacogenomics. Pharmacogenomics can be utilized to predict whether a pharmacologic therapy will be effective or to identify patients at risk for treatment-related toxicity. Although genetic tests are typically ordered for a distinct clinical purpose, the genetic variants that are found may have additional implications for either disease or pharmacology. This review will address multiple examples of germline genetic variants that are informative for both disease and pharmacogenomics...
October 1, 2017: Physiological Genomics
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