R270C polymorphism leads to loss of function of the canine P2X7 receptor
This study aimed to assess the functional impact of P2X7 variation in a random sample of the canine population. Blood and genomic DNA were obtained from 69 dogs selected as representatives of a cross section of different breeds. P2X7 function was determined by flow cytometric measurements of dye uptake and patch-clamp measurements of inward currents. P2X7 expression was determined by immunoblotting and immunocytochemistry. Sequencing was used to identify P2RX7 gene polymorphisms. P2X7 was cloned from an English springer spaniel, and point mutations were introduced into this receptor by site-directed mutagenesis. The relati...
Source: Physiological Genomics - July 15, 2014 Category: Genetics & Stem Cells Authors: Spildrejorde, M., Bartlett, R., Stokes, L., Jalilian, I., Peranec, M., Sluyter, V., Curtis, B. L., Skarratt, K. K., Skora, A., Bakhsh, T., Seavers, A., McArthur, J. D., Dowton, M., Sluyter, R. Tags: General Interest Source Type: research
Mitochondrial respiration and microRNA expression in right and left atrium of patients with atrial fibrillation
This study aims to investigate mitochondrial function and miR expression in the right (RA) and left atria (LA) of patients with AF and sinus rhythm (SR). Myocardial tissue from the RA and LA appendages was investigated in 37 patients with AF (n = 21) or SR (n = 16) undergoing coronary artery bypass surgery and/or heart valve surgery. Mitochondrial respiration was measured in situ after tissue permeabilization by saponin. MiR expression was assessed by miR array and real-time quantitative reverse-transcription polymerase chain reaction. Maximal mitochondrial respiratory rate was increased in both RA and LA tissue of patient...
Source: Physiological Genomics - July 15, 2014 Category: Genetics & Stem Cells Authors: Slagsvold, K. H., Johnsen, A. B., Rognmo, O., Hoydal, M. A., Wisloff, U., Wahba, A. Tags: Call for Papers: Mitochondrial Metabolism Source Type: research
High cardiorespiratory fitness can reduce glycated hemoglobin levels regardless of polygenic risk for Type 2 diabetes mellitus in nondiabetic Japanese men
High cardiorespiratory fitness (CRF) is associated with a reduced risk of Type 2 diabetes mellitus (T2DM) and improved β-cell function; genetic factors also determine these risks. This cross-sectional study investigated whether CRF modifies the association of polygenic risk of T2DM with glucose metabolism in nondiabetic Japanese men. Fasting plasma glucose, insulin, and glycated hemoglobin (HbA1c) levels were measured in 174 Japanese men (age: 20–79 yr). β-Cell function and insulin resistance were evaluated by calculating HOMA-β and HOMA-IR, respectively. CRF was assessed by measuring maximal oxygen up...
Source: Physiological Genomics - July 15, 2014 Category: Genetics & Stem Cells Authors: Tanisawa, K., Ito, T., Sun, X., Ise, R., Oshima, S., Cao, Z.-B., Sakamoto, S., Tanaka, M., Higuchi, M. Tags: Call for Papers: Physiological Genomics of Exercise in Health and Disease Source Type: research
Transcriptional atlas of cardiogenesis maps congenital heart disease interactome
Mammalian heart development is built on highly conserved molecular mechanisms with polygenetic perturbations resulting in a spectrum of congenital heart diseases (CHD). However, knowledge of cardiogenic ontogeny that regulates proper cardiogenesis remains largely based on candidate-gene approaches. Mapping the dynamic transcriptional landscape of cardiogenesis from a genomic perspective is essential to integrate the knowledge of heart development into translational applications that accelerate disease discovery efforts toward mechanistic-based treatment strategies. Herein, we designed a time-course transcriptome analysis t...
Source: Physiological Genomics - July 1, 2014 Category: Genetics & Stem Cells Authors: Li, X., Martinez-Fernandez, A., Hartjes, K. A., Kocher, J.-P. A., Olson, T. M., Terzic, A., Nelson, T. J. Tags: Omics Technologies and Applications Source Type: research
Comprehensive characterization of glioblastoma tumor tissues for biomarker identification using mass spectrometry-based label-free quantitative proteomics
The objective of our study is to identify and characterize proteins that are differentially expressed in GBM to better understand their interactions and functions that lead to the disease condition. Further identification of upstream regulators will provide new potential therapeutic targets. We analyzed GBM tumors by SDS-PAGE fractionation with internal DNA markers followed by liquid chromatography-tandem mass spectrometry (MS). Brain tissue specimens obtained for clinical purposes during epilepsy surgeries were used as controls, and the quantification of MS data was performed by label-free spectral counting. The different...
Source: Physiological Genomics - July 1, 2014 Category: Genetics & Stem Cells Authors: Heroux, M. S., Chesnik, M. A., Halligan, B. D., Al-Gizawiy, M., Connelly, J. M., Mueller, W. M., Rand, S. D., Cochran, E. J., LaViolette, P. S., Malkin, M. G., Schmainda, K. M., Mirza, S. P. Tags: General Interest Source Type: research
Transcriptional profiling reveals ductus arteriosus-specific genes that regulate vascular tone
This study identifies subsets of genes that are enriched in the DA that may be used to develop DA-specific drugs. Ion channels that regulate DA tone, including BKCa channels, are promising targets. Specifically, BKCa channel agonists like NS1619 maintain DA patency even in the presence of O2 and may be clinically useful. (Source: Physiological Genomics)
Source: Physiological Genomics - July 1, 2014 Category: Genetics & Stem Cells Authors: Shelton, E. L., Ector, G., Galindo, C. L., Hooper, C. W., Brown, N., Wilkerson, I., Pfaltzgraff, E. R., Paria, B. C., Cotton, R. B., Stoller, J. Z., Reese, J. Tags: General Interest Source Type: research
Rational combination of dual PI3K/mTOR blockade and Bcl-2/-xL inhibition in AML
Acute myeloid leukemia (AML) continues to represent an area of critical unmet need with respect to new and effective targeted therapies. The Bcl-2 family of pro- and antiapoptotic proteins stands at the crossroads of cellular survival and death, and the expression of and interactions between these proteins determine tumor cell fate. Malignant cells, which are often primed for apoptosis, are particularly vulnerable to the simultaneous disruption of cooperative survival signaling pathways. Indeed, the single agent activity of agents such as mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase kinase (MEK...
Source: Physiological Genomics - July 1, 2014 Category: Genetics & Stem Cells Authors: Vachhani, P., Bose, P., Rahmani, M., Grant, S. Tags: General Interest Source Type: research
Advanced methods for the analysis of chromatin-associated proteins
DNA-protein interactions are central to gene expression and chromatin regulation and have become one of the main focus areas of the ENCODE consortium. Advances in mass spectrometry and associated technologies have facilitated studies of these interactions, revealing many novel DNA-interacting proteins and histone posttranslational modifications. Proteins interacting at a single locus or at multiple loci have been targeted in these recent studies, each requiring a separate analytical strategy for isolation and analysis of DNA-protein interactions. The enrichment of target chromatin fractions occurs via a number of methods i...
Source: Physiological Genomics - July 1, 2014 Category: Genetics & Stem Cells Authors: Guillen-Ahlers, H., Shortreed, M. R., Smith, L. M., Olivier, M. Tags: General Interest Source Type: research
Identification of the crucial molecular events during the large-scale myoblast fusion in sheep
It is well known that in sheep most myofibers are formed before birth; however, the crucial myogenic stage and the cellular and molecular mechanisms underpinning phenotypic variation of fetal muscle development remain to be ascertained. We used histological, microarray, and quantitative real-time PCR (qPCR) methods to examine the developmental characteristics of fetal muscle at 70, 85, 100, 120, and 135 days of gestation in sheep. We show that day 100 is an important checkpoint for change in muscle transcriptome and histomorphology in fetal sheep and that the period of 85–100 days is the vital developmental stage for...
Source: Physiological Genomics - June 15, 2014 Category: Genetics & Stem Cells Authors: Wei, C., Li, L., Su, H., Xu, L., Lu, J., Zhang, L., Liu, W., Ren, H., Du, L. Tags: Omics Technologies and Applications Source Type: research
Protease inhibitor 15, a candidate gene for abdominal aortic internal elastic lamina ruptures in the rat
In this study, we further dissected the above-mentioned QTL by creating a new panel of LOU.BN(chr5) congenic and subcongenic lines and reduced the locus to 5.2 Mb. Then we studied 1,002 heterogeneous stock (HS) rats, whose phenotyping revealed a low prevalence and high variability for RIEL. High-resolution mapping in the HS panel detected the major locus on chromosome 5 (log P > 35) and refined it to 1.4 Mb. Subsequently, RNA-seq analysis on AA of BN, congenics, and LOU revealed expression differences for only protease inhibitor 15 (Pi15) gene and a putative long intergenic noncoding RNA (lincRNA) within the linkage reg...
Source: Physiological Genomics - June 15, 2014 Category: Genetics & Stem Cells Authors: Falak, S., Schafer, S., Baud, A., Hummel, O., Schulz, H., Gauguier, D., Hubner, N., Osborne-Pellegrin, M. Tags: Molecular Genetics of Complex Traits Source Type: research
NFE2L2 polymorphisms, mortality, and metabolism in the general population
This study shows for the first time that NFE2L2 is associated with reduced risk of all-cause, cardiovascular and COPD mortality in humans. (Source: Physiological Genomics)
Source: Physiological Genomics - June 15, 2014 Category: Genetics & Stem Cells Authors: Figarska, S. M., Vonk, J. M., Boezen, H. M. Tags: General Interest Source Type: research
Characterization of biological pathways associated with a 1.37 Mbp genomic region protective of hypertension in Dahl S rats
The goal of the present study was to narrow a region of chromosome 13 to only several genes and then apply unbiased statistical approaches to identify molecular networks and biological pathways relevant to blood-pressure salt sensitivity in Dahl salt-sensitive (SS) rats. The analysis of 13 overlapping subcongenic strains identified a 1.37 Mbp region on chromosome 13 that influenced the mean arterial blood pressure by at least 25 mmHg in SS rats fed a high-salt diet. DNA sequencing and analysis filled genomic gaps and provided identification of five genes in this region, Rfwd2, Fam5b, Astn1, Pappa2, and Tnr. A cross-platfor...
Source: Physiological Genomics - June 1, 2014 Category: Genetics & Stem Cells Authors: Cowley, A. W., Moreno, C., Jacob, H. J., Peterson, C. B., Stingo, F. C., Ahn, K. W., Liu, P., Vannucci, M., Laud, P. W., Reddy, P., Lazar, J., Evans, L., Yang, C., Kurth, T., Liang, M. Tags: General Interest Source Type: research
Contractile abnormalities of mouse muscles expressing hyperkalemic periodic paralysis mutant NaV1.4 channels do not correlate with Na+ influx or channel content
This study provides evidence that HyperKPP phenotype does not depend solely on the NaV1.4 content or Na+ influx and that the diaphragm does not depend solely on Na+-K+ pumps to ameliorate the phenotype. (Source: Physiological Genomics)
Source: Physiological Genomics - June 1, 2014 Category: Genetics & Stem Cells Authors: Lucas, B., Ammar, T., Khogali, S., DeJong, D., Barbalinardo, M., Nishi, C., Hayward, L. J., Renaud, J.-M. Tags: General Interest Source Type: research
Identification of genetic loci associated with different responses to high-fat diet-induced obesity in C57BL/6N and C57BL/6J substrains
We have recently demonstrated that C57BL/6NTac and C57BL/6JRj substrains are significantly different in their response to high-fat diet-induced obesity (DIO). The C57BL/6JRj substrain seems to be protected from DIO and genetic differences between C57BL/6J and C57BL/6N substrains at 11 single nucleotide polymorphism (SNP) loci have been identified. To define genetic variants as well as differences in parameters of glucose homeostasis and insulin sensitivity between C57BL/6NTac and C57BL/6JRj substrains that may explain the different response to DIO, we analyzed 208 first backcross (BC1) hybrids of C57BL/6NTac and C57BL/6JRj...
Source: Physiological Genomics - June 1, 2014 Category: Genetics & Stem Cells Authors: Heiker, J. T., Kunath, A., Kosacka, J., Flehmig, G., Knigge, A., Kern, M., Stumvoll, M., Kovacs, P., Bluher, M., Kloting, N. Tags: Model Organisms Source Type: research
Unique transcriptomic signature of omental adipose tissue in Ossabaw swine: a model of childhood obesity
To better understand the impact of childhood obesity on intra-abdominal adipose tissue phenotype, a complete transcriptomic analysis using deep RNA-sequencing (RNA-seq) was performed on omental adipose tissue (OMAT) obtained from lean and Western diet-induced obese juvenile Ossabaw swine. Obese animals had 88% greater body mass, 49% greater body fat content, and a 60% increase in OMAT adipocyte area (all P < 0.05) compared with lean pigs. RNA-seq revealed a 37% increase in the total transcript number in the OMAT of obese pigs. Ingenuity Pathway Analysis showed transcripts in obese OMAT were primarily enriched in the fol...
Source: Physiological Genomics - May 15, 2014 Category: Genetics & Stem Cells Authors: Toedebusch, R. G., Roberts, M. D., Wells, K. D., Company, J. M., Kanosky, K. M., Padilla, J., Jenkins, N. T., Perfield, J. W., Ibdah, J. A., Booth, F. W., Rector, R. S. Tags: Call for Papers: NextGen Sequencing Technology-based Dissection of Physiological Systems Source Type: research
