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Physiological Genomics

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https://www.readbyqxmd.com/read/28550089/advancing-precision-medicine-in-healthcare
#1
Olivia M Dong, Tim Wiltshire
The incorporation of precision medicine into the clinical setting is becoming increasingly feasible with the availability of more affordable genetic sequencing technologies and successful genetic associations with phenotypes, especially in the pharmacogenomic field. Although substantial progress has been made to ensure successful uptake of pharmacogenomic testing in the clinical setting already, many challenges still remain for sustainable implementation. The importance of pharmacogenomic information in patient care, identifying key barriers, and proposed solutions for advancing pharmacogenomic implementation will be discussed...
May 26, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28550088/cardiac-telomere-length-in-heart-development-function-and-disease
#2
Scott A Booth, Fadi J Charchar
Telomeres are repetitive nucleoprotein structures at chromosome ends and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function...
May 26, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28550087/transcriptional-networks-in-rodent-models-support-a-role-for-gut-brain-communication-in-neurogenic-hypertension-a-review-of-the-evidence
#3
Jasenka Zubcevic, Ashley Baker, Christopher J Martyniuk
Hypertension (HTN) is the most prevalent condition observed in primary health care. Hypertension shows complex etiology, and neuroinflammation, overactive sympathetic drive, and the microbiome are associated with the disease. To obtain mechanistic perspective into neurogenic HTN, we first constructed a framework for transcriptional regulators of the disease using the Comparative Toxicogenomics Database. This approach yielded a core group of 178 transcripts that are prevalent in HTN, including leptin and neuropeptide Y...
May 26, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28500253/linc00341-exerts-an-anti-inflammatory-effect-on-endothelial-cells-by-repressing-vcam1
#4
Tse-Shun Huang, Kuei-Chun Wang, Sara Quon, Phu Nguyen, Ting-Yu Chang, Zhen Chen, Yi-Shuan Li, Shankar Subramaniam, John Y-J Shyy, Shu Chien
The long non-coding RNAs (lncRNAs), which constitute a large portion of the transcriptome, have gained intense research interest because of their roles in regulating physiological and pathophysiological functions in the cell. We identified from RNA-seq profiling a set of lncRNAs in cultured human umbilical vein endothelial cells (HUVECs) that are differentially regulated by atheroprotective vs. atheroprone shear flows. Among the comprehensively annotated lncRNAs, including both known and novel transcripts, LINC00341 is one of the most abundant lncRNAs in endothelial cells...
May 12, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28500252/transcriptome-profiling-reveals-novel-bmi-and-sex-specific-gene-expression-signature-for-human-cardiac-hypertrophy
#5
Mackenzie S Newman, Tina Nguyen, Michael J Watson, Robert Hull, Han-Gang Yu
BACKGROUND: How obesity or sex may affect the gene expression profiles of human cardiac hypertrophy is unknown. We hypothesized that body-mass index (BMI) and sex can affect gene expression profiles of cardiac hypertrophy. RESULTS: Human heart tissues were grouped according to sex (male, female), BMI (lean<25 kg/m(2), obese>30 kg/m(2)), or left ventricular hypertrophy (LVH) and non-LVH non-failed controls (NF). We identified 24 DE genes comparing female to male samples...
May 12, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28455310/exercise-induced-modification-of-the-skeletal-muscle-transcriptome-in-arabian-horses
#6
Katarzyna Ropka-Molik, Monika Stefaniuk-Szmukier, Kacper Żukowski, Katarzyna Piórkowska, Monika Bugno-Poniewierska
It has been found that Arabian and Thoroughbred horses differ in muscle fiber structure and thus in physiological changes occurring in muscles during exercise. The aim of the present study was to identify the global gene expression modifications that occur in skeletal muscle following a training regime to prepare for flat racing. Whole transcriptomes of muscle (gluteus medius) were compared between three time points of tissue collection: T0 (untrained horses), T1 (horses after intense gallop phase) and T2 (horses at the end of racing season), 23 samples in total...
April 28, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28455309/big-calcium-activated-potassium-channel-in-skeletal-muscle-structure-function-and-pharmacological-perspectives
#7
Fatima Maqoud, Michela Cetrone, Antonietta Mele, Domenico Tricarico
The large-conductance Ca(2+)-activated K(+) (BK) channel is broadly expressed in various mammalian cells and tissues such as neurons, skeletal muscles (sarco-BK), and smooth muscles. These channels are activated by changes in membrane electrical potential and by increases in the concentration of intracellular calcium ion (Ca(2+)). The large-conductance Ca(2+)-activated K(+) (BK) channel is subjected to many mechanisms that add diversity to the BK channel α subunit gene. These channels are indeed subject to alternative splicing, auxiliary subunits modulation, post-translational modifications and protein-protein interactions...
April 28, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28432191/gene-expression-effects-of-glucocorticoid-and-mineralocorticoid-receptor-agonists-and-antagonists-on-normal-human-skeletal-muscle
#8
Jessica A Chadwick, James Spencer Hauck, Celso E Gomez-Sanchez, Elise P Gomez-Sanchez, Jill A Rafael-Fortney
Mineralocorticoid and glucocorticoid receptors are closely related steroid hormone receptors that regulate gene expression through many of the same hormone response elements. However, their transcriptional activities and effects in skeletal muscles are largely unknown. We recently identified mineralocorticoid receptors (MR) in skeletal muscles after finding that combined treatment with the angiotensin-converting enzyme inhibitor lisinopril and MR antagonist spironolactone was therapeutic in Duchenne muscular dystrophy mouse models...
April 21, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28389524/de-novo-rna-sequence-assembly-during-in-vivo-inflammatory-stress-reveals-hundreds-of-unannotated-lincrnas-in-human-blood-cd14-monocytes-and-in-adipose-tissue
#9
Chenyi Xue, Xuan Zhang, Hanrui Zhang, Jane F Ferguson, Ying Wang, Christine Hinkle, Mingyao Li, Muredach P Reilly
Long intergenic noncoding RNAs (lincRNAs) have emerged as key regulators of cellular functions and physiology. Yet functional lincRNAs often have low, context-specific and tissue-specific expression. We hypothesized that many human monocyte and adipose lincRNAs would be absent in current public annotations due to lincRNA tissue specificity, modest sequencing depth in public data, limitations of transcriptome assembly algorithms and lack of dynamic physiological contexts. Deep RNA-seq was performed in peripheral blood CD14+ monocytes (monocytes; average ~247 million reads per sample) and adipose tissue (average ~378 million reads per sample) collected before and after human experimental endotoxemia, an in vivo inflammatory stress, to identify tissue-specific and clinically relevant lincRNAs...
April 7, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28341621/cancer-cachexia-induced-muscle-atrophy-evidence-for-alterations-in-micrornas-important-for-muscle-size
#10
David Edward Lee, Jacob L Brown, Megan E Rosa-Caldwell, Thomas A Blackwell, Richard A Perry, Lemuel A Brown, Bhuwan Khatri, Dongwon Seo, Walter Gay Bottje, Tyrone Anthony Washington, Michael P Wiggs, Byung-Whi Kong, Nicholas Perry Greene
Muscle atrophy is a hallmark of cancer cachexia resulting in impaired function and quality of life and cachexia is the immediate cause of death for 20-40% of cancer patients. Multiple microRNAs (miRNAs) have been identified as being involved in muscle development and atrophy, however less is known specifically on miRNAs in cancer cachexia. PURPOSE: The purpose of this investigation was to examine the miRNA profile of skeletal muscle atrophy induced by cancer cachexia to uncover potential miRNAs involved with this catabolic condition...
March 24, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28389525/role-of-renal-transporters-and-novel-regulatory-interactions-in-the-tal-that-control-blood-pressure
#11
REVIEW
Lesley A Graham, Anna F Dominiczak, Nicholas R Ferreri
Hypertension (HTN), a major public health issue is currently the leading factor in the global burden of disease, where associated complications account for 9.4 million deaths worldwide every year. Excessive dietary salt intake is among the environmental factors that contribute to HTN, known as salt sensitivity. The heterogeneity of salt sensitivity and the multiple mechanisms that link high salt intake to increases in blood pressure are of upmost importance for therapeutic application. A continual increase in the kidney's reabsorption of sodium (Na(+)) relies on sequential actions at various segments along the nephron...
May 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28258078/short-term-low-magnesium-diet-reduces-autoimmune-arthritis-severity-and-synovial-tissue-gene-expression
#12
Max Brenner, Teresina Laragione, Pércio S Gulko
Magnesium has been suggested to have anti-inflammatory properties in short-term, mostly in vitro studies. To examine the effect of dietary magnesium modifications in arthritis severity and joint damage DA rats were placed on one of three diet regimens before the induction of autoimmune pristane-induced arthritis (PIA): a 4 wk low-magnesium diet, normal diet, and a magnesium-supplemented diet. The diets were switched to a normal diet 14 days after the induction of PIA (typical time of disease onset). Arthritis severity was scored for 38 days, and joints were examined by histology and quantitative PCR for proinflammatory genes...
April 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28213571/mir-146a-b-a-family-with-shared-seeds-and-different-roots
#13
REVIEW
Mark R Paterson, Alison J Kriegel
MicroRNAs are small, noncoding, RNAs known for their powerful modulation of molecular processes, making them a major focus for studying pathological mechanisms. The human miR-146 family of microRNAs consists of two member genes, MIR146A and MIR146B These two microRNAs are located on different chromosomes and exhibit differential regulation in many cases. However, they are nearly identical in sequence, sharing a seed region, and are thus predicted to target the same set of genes. A large proportion of the microRNA (miR)-146 literature focuses on its role in regulating the innate immune response in the context of various pathologies by modulating two widely studied target genes in the toll-like receptor signaling cascade...
April 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28213570/blunted-transcriptional-response-to-skeletal-muscle-ischemia-in-rats-with-chronic-kidney-disease-potential-role-for-impaired-ischemia-induced-angiogenesis
#14
Rafael U Heiss, Fabian B Fahlbusch, Johannes Jacobi, Christoph Daniel, Arif B Ekici, Nada Cordasic, Kerstin Amann, Andrea Hartner, Karl F Hilgers
Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. Previous studies indicated an impairment of ischemia-induced angiogenesis in skeletal muscle of rats with CKD. We performed a systematic comparison of early gene expression in response to ischemia in rats with or without CKD to identify potential molecular mechanisms underlying impaired angiogenesis in CKD. CKD was induced in male rats by 5/6 nephrectomy (SNX); control rats were sham operated (sham). Eight weeks later, ischemia of the right limb was induced by ligation and resection of the femoral artery...
April 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28159858/transcriptomic-alterations-in-the-brain-of-painted-turtles-chrysemys-picta-developmentally-exposed-to-bisphenol-a-or-ethinyl-estradiol
#15
Lindsey K Manshack, Caroline M Conard, Sara J Bryan, Sharon L Deem, Dawn K Holliday, Nathan J Bivens, Scott A Givan, Cheryl S Rosenfeld
Developmental exposure of turtles and other reptiles to endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA) and ethinyl estradiol (EE), can stimulate partial to full gonadal sex-reversal in males. We have also recently shown that in ovo exposure to either EDC can induce similar sex-dependent behavioral changes typified by improved spatial learning and memory or possibly feminized brain responses. Observed behavioral changes are presumed to be due to BPA- and EE-induced brain transcriptomic alterations during development...
April 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28130426/genetic-analysis-of-10-pedigrees-with-inherited-retinal-degeneration-by-exome-sequencing-and-phenotype-genotype-association
#16
Pooja Biswas, Jacque L Duncan, Bruno Maranhao, Igor Kozak, Kari Branham, Luis Gabriel, Jonathan H Lin, Giulio Barteselli, Mili Navani, John Suk, Michelle Parke, Catherine Schlechter, Richard G Weleber, John R Heckenlively, Gislin Dagnelie, Pauline Lee, S Amer Riazuddin, Radha Ayyagari
Our purpose was to identify causative mutations and characterize the phenotype associated with the genotype in 10 unrelated families with autosomal recessive retinal degeneration. Ophthalmic evaluation and DNA isolation were carried out in 10 pedigrees with inherited retinal degenerations (IRD). Exomes of probands from eight pedigrees were captured using Nimblegen V2/V3 or Agilent V5+UTR kits, and sequencing was performed on Illumina HiSeq. The DHDDS gene was screened for mutations in the remaining two pedigrees with Ashkenazi Jewish ancestry...
April 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28130428/hla-gene-expression-is-altered-in-whole-blood-and-placenta-from-women-who-later-developed-preeclampsia
#17
Heather Y Small, Christine Akehurst, Liliya Sharafetdinova, Martin W McBride, John D McClure, Scott W Robinson, David M Carty, Dilys J Freeman, Christian Delles
Preeclampsia is a multisystem disease that significantly contributes to maternal and fetal morbidity and mortality. In this study, we used a non-biased microarray approach to identify dysregulated genes in maternal whole blood samples which may be associated with the development of preeclampsia. Whole blood samples were obtained at 28 wk of gestation from 5 women who later developed preeclampsia (cases) and 10 matched women with normotensive pregnancies (controls). Placenta samples were obtained from an independent cohort of 19 women with preeclampsia matched with 19 women with normotensive pregnancies...
March 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28130427/nephron-number-hypertension-and-ckd-physiological-and-genetic-insight-from-humans-and-animal-models
#18
REVIEW
Xuexiang Wang, Michael R Garrett
The kidneys play a vital role in the excretion of waste products and the regulation of electrolytes, maintenance of acid-base balance, regulation of blood pressure, and production of several hormones. Any alteration in the structure of the nephron (basic functional unit of the kidney) can have a major impact on the kidney's ability to work efficiently. Progressive decline in kidney function can lead to serious illness and ultimately death if not treated by dialysis or transplantation. While there have been numerous studies that implicate lower nephron numbers as being an important factor in influencing susceptibility to developing hypertension and chronic kidney disease, a direct association has been difficult to establish because of three main limitations: 1) the large variation in nephron number observed in the human population; 2) no established reliable noninvasive methods to determine nephron complement; and 3) to date, nephron measurements have been done after death, which doesn't adequately account for potential loss of nephrons with age or disease...
March 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28087757/alternative-transcription-of-sodium-bicarbonate-transporter-slc4a7-gene-enhanced-by-single-nucleotide-polymorphisms
#19
Hae Jeong Park, Soojung Lee, Eunji Ju, Jayre A Jones, Inyeong Choi
Genome-wide association studies have identified the single nucleotide polymorphism (SNP) rs3278 in the human SLC4A7 gene as one of the marker loci for addiction vulnerability. This marker is located in an intron of the gene, and its genomic role has been unknown. In this study, we examined rs3278 and three adjacent SNPs prevalent in alcoholics for their effects on an alternative promoter that would lead to the production of the NH2-terminally truncated protein NBCn1ΔN450, missing the first 450 amino acids...
March 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28087756/fine-mapping-of-genes-determining-extrafusal-fiber-properties-in-murine-soleus-muscle
#20
A M Carroll, R Cheng, E S R Collie-Duguid, C Meharg, M E Scholz, S Fiering, J L Fields, A A Palmer, A Lionikas
Muscle fiber cross-sectional area (CSA) and proportion of different fiber types are important determinants of muscle function and overall metabolism. Genetic variation plays a substantial role in phenotypic variation of these traits; however, the underlying genes remain poorly understood. This study aimed to map quantitative trait loci (QTL) affecting differences in soleus muscle fiber traits between the LG/J and SM/J mouse strains. Fiber number, CSA, and proportion of oxidative type I fibers were assessed in the soleus of 334 genotyped female and male mice of the F34 generation of advanced intercross lines (AIL) derived from the LG/J and SM/J strains...
March 1, 2017: Physiological Genomics
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