Preeclampsia, of mice and women
Preeclampsia (PE) is a devastating disorder of pregnancy that affects up to 8% of pregnant women in the United States. The diagnosis of PE is made by the presentation of new-onset hypertension, ≥140 mmHg systolic blood pressure (BP) or ≥90 mmHg diastolic BP, and either proteinuria or another accompanying sign/symptom, such as renal insufficiency, thrombocytopenia, hepatic dysfunction, pulmonary edema, or cerebral/visual. These signs can occur suddenly and without warning. PE that presents before 34 wk of gestation is considered early onset and carries a greater risk for perinatal morbidity/mortality than late-onset P...
Source: Physiological Genomics - July 31, 2016 Category: Genetics & Stem Cells Authors: Sones, J. L., Davisson, R. L. Tags: Call for Papers: Systems Biology and Polygenic Traits Source Type: research
Coronary artery disease susceptibility gene ADTRP regulates cell cycle progression, proliferation, and apoptosis by global gene expression regulation
The ADTRP gene encodes the androgen-dependent TFPI-regulating protein and is a susceptibility gene for contrary artery disease (CAD). We performed global gene expression profiling for ADTRP knock-down using microarrays in human HepG2 cells. Follow-up real-time RT-PCR analysis demonstrated that ADTRP knock-down regulates a diverse set of genes, including upregulation of seven histone genes, downregulation of multiple cell cycle genes (CCND1, CDK4, and CDKN1A), and upregulation of apoptosis genes (CASP7 and PDCD2) in HepG2 cells and endothelial cells. Consistently, ADTRP increases the number of S phase cells during cell cycl...
Source: Physiological Genomics - July 31, 2016 Category: Genetics & Stem Cells Authors: Luo, C., Wang, F., Qin, S., Chen, Q., Wang, Q. K. Tags: Call for Papers: Single Cell Analysis Source Type: research
Interactions between the colonic transcriptome, metabolome, and microbiome in mouse models of obesity-induced intestinal cancer
Obesity is a significant risk factor for colorectal cancer (CRC); however, the relative contribution of high-fat (HF) consumption and excess adiposity remains unclear. It is becoming apparent that obesity perturbs both the intestinal microbiome and metabolome, and each has the potential to induce protumorigenic changes in the epithelial transcriptome. The physiological consequences and the degree to which these different biologic systems interact remain poorly defined. To understand the mechanisms by which obesity drives colonic tumorigenesis, we profiled the colonic epithelial transcriptome of HF-fed and genetically obese...
Source: Physiological Genomics - July 31, 2016 Category: Genetics & Stem Cells Authors: Pfalzer, A. C., Kamanu, F. K., Parnell, L. D., Tai, A. K., Liu, Z., Mason, J. B., Crott, J. W. Tags: Call for Papers: Gut Microbiota in Health and Disease Source Type: research
Haplotype and diplotype analyses of variation in ERCC5 transcription cis-regulation in normal bronchial epithelial cells
Excision repair cross-complementation group 5 (ERCC5) gene plays an important role in nucleotide excision repair, and dysregulation of ERCC5 is associated with increased lung cancer risk. Haplotype and diplotype analyses were conducted in normal bronchial epithelial cells (NBEC) to better understand mechanisms responsible for interindividual variation in transcript abundance regulation of ERCC5. We determined genotypes at putative ERCC5 cis-regulatory SNPs (cis-rSNP) rs751402 and rs2296147, and marker SNPs rs1047768 and rs17655. ERCC5 allele-specific transcript abundance was assessed by a recently developed targeted sequen...
Source: Physiological Genomics - July 24, 2016 Category: Genetics & Stem Cells Authors: Zhang, X., Crawford, E. L., Blomquist, T. M., Khuder, S. A., Yeo, J., Levin, A. M., Willey, J. C. Tags: Physiological Genomics of Cell States and Their Regulation and Single Cell Genomics Source Type: research
Loss of bone marrow adrenergic beta 1 and 2 receptors modifies transcriptional networks, reduces circulating inflammatory factors, and regulates blood pressure
This study generates new insight into the molecular events that underlie the interaction between the sympathetic drive and IS in modulation of BP. (Source: Physiological Genomics)
Source: Physiological Genomics - July 24, 2016 Category: Genetics & Stem Cells Authors: Ahmari, N., Schmidt, J. T., Krane, G. A., Malphurs, W., Cunningham, B. E., Owen, J. L., Martyniuk, C. J., Zubcevic, J. Tags: Call for Papers Source Type: research
Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels
In this study bone marrow transcriptomes were compared among thirteen-lined ground squirrels collected in July, winter torpor, and winter interbout arousal (IBA). The results were consistent with a suppression of acquired immune responses, and a shift to innate immune responses during hibernation through higher complement expression. Consistent with the increase in adipocytes found in bone marrow of hibernators, expression of genes associated with white adipose tissue are higher during hibernation. Genes that should strengthen the bone by increasing extracellular matrix were higher during hibernation, especially the collag...
Source: Physiological Genomics - June 30, 2016 Category: Genetics & Stem Cells Authors: Cooper, S. T., Sell, S. S., Fahrenkrog, M., Wilkinson, K., Howard, D. R., Bergen, H., Cruz, E., Cash, S. E., Andrews, M. T., Hampton, M. Tags: Comparative, Statistical, and Computational Genomics and Model Organism Databases Source Type: research
Comprehensive database of human E3 ubiquitin ligases: application to aquaporin-2 regulation
Aquaporin-2 (AQP2) is regulated in part via vasopressin-mediated changes in protein half-life that are in turn dependent on AQP2 ubiquitination. Here we addressed the question, "What E3 ubiquitin ligase is most likely to be responsible for AQP2 ubiquitination?" using large-scale data integration based on Bayes' rule. The first step was to bioinformatically identify all E3 ligase genes coded by the human genome. The 377 E3 ubiquitin ligases identified in the human genome, consisting predominant of HECT, RING, and U-box proteins, have been used to create a publically accessible and downloadable online database (https://hpcwe...
Source: Physiological Genomics - June 30, 2016 Category: Genetics & Stem Cells Authors: Medvar, B., Raghuram, V., Pisitkun, T., Sarkar, A., Knepper, M. A. Tags: General Interest Source Type: research
Effect of selective expression of dominant-negative PPAR{gamma} in pro-opiomelanocortin neurons on the control of energy balance
Peroxisome proliferator-activated receptor- (PPAR), a master regulator of adipogenesis, was recently shown to affect energy homeostasis through its actions in the brain. Deletion of PPAR in mouse brain, and specifically in the pro-opiomelanocortin (POMC) neurons, results in resistance to diet-induced obesity. To study the mechanisms by which PPAR in POMC neurons controls energy balance, we constructed a Cre-recombinase-dependent conditionally activatable transgene expressing either wild-type (WT) or dominant-negative (P467L) PPAR and the tdTomato reporter. Inducible expression of both forms of PPAR was validated in cells i...
Source: Physiological Genomics - June 30, 2016 Category: Genetics & Stem Cells Authors: Stump, M., Guo, D.-F., Lu, K.-T., Mukohda, M., Liu, X., Rahmouni, K., Sigmund, C. D. Tags: Physiological and Genetic Control of Neural Function Source Type: research
Retinoic acid and sodium butyrate suppress the cardiac expression of hypertrophic markers and proinflammatory mediators in Npr1 gene-disrupted haplotype mice
The objective of the present study was to examine the genetically determined differences in the natriuretic peptide receptor-A (NPRA) gene (Npr1) copies affecting the expression of cardiac hypertrophic markers, proinflammatory mediators, and matrix metalloproteinases (MMPs) in a gene-dose-dependent manner. We determined whether stimulation of Npr1 by all-trans retinoic acid (RA) and histone deacetylase (HDAC) inhibitor sodium butyric acid (SB) suppress the expression of cardiac disease markers. In the present study, we utilized Npr1 gene-disrupted heterozygous (Npr1+/–, 1-copy), wild-type (Npr1+/+, 2-copy), gene-dupl...
Source: Physiological Genomics - June 30, 2016 Category: Genetics & Stem Cells Authors: Subramanian, U., Kumar, P., Mani, I., Chen, D., Kessler, I., Periyasamy, R., Raghavaraju, G., Pandey, K. N. Tags: Genomic and ' Polyomic Studies of Cardiovascular and Inflammatory Diseases Source Type: research
Discovery and identification of candidate sex-related genes based on transcriptome sequencing of Russian sturgeon (Acipenser gueldenstaedtii) gonads
As the Russian sturgeon (Acipenser gueldenstaedtii) is an important food and is the main source of caviar, it is necessary to discover the genes associated with its sex differentiation. However, the complicated life and maturity cycles of the Russian sturgeon restrict the accurate identification of sex in early development. To generate a first look at specific sex-related genes, we sequenced the transcriptome of gonads in different development stages (1, 2, and 5 yr old stages) with next-generation RNA sequencing. We generated >60 million raw reads, and the filtered reads were assembled into 263,341 contigs, which produ...
Source: Physiological Genomics - June 30, 2016 Category: Genetics & Stem Cells Authors: Chen, Y., Xia, Y., Shao, C., Han, L., Chen, X., Yu, M., Sha, Z. Tags: Call for Papers: Systems Biology and Polygenic Traits Source Type: research
High-throughput sequencing reveals differential expression of miRNAs in prehierarchal follicles of laying and brooding geese
This study revealed the miRNAs that were directly involved in follicular atresia, and our results added to the understanding of the functional involvement of miRNAs during specific stages of follicle development. (Source: Physiological Genomics)
Source: Physiological Genomics - June 30, 2016 Category: Genetics & Stem Cells Authors: Yu, J., He, K., Ren, T., Lou, Y., Zhao, A. Tags: Call for Papers: Systems Biology and Polygenic Traits Source Type: research
Minireview: Role of genetic changes of faciogenital dysplasia protein 1 in human disease
The FGD1 gene encodes for a guanine exchange factor (GEF) protein that specifically activates the Rho GTPase Cdc42. For cellular migration, Cdc42 is a key molecular switch that regulates cytoskeleton restructuring, gene transcription, cellular morphology, extension, and cell adhesion. In the past decade, germline mutations in the FGD1 gene have been associated with a rare X-linked disorder known as faciogenital dysplasia (FGDY). Malformations are consistent with a loss of cellular migration during embryonic development. Insertion and deletion mutations in FGD1 result in a frameshift causing inactivation of fgd1 protein. Si...
Source: Physiological Genomics - June 30, 2016 Category: Genetics & Stem Cells Authors: Pedigo, N. G., Van Delden, D., Walters, L., Farrell, C. L. Tags: Call for Papers: Systems Biology and Polygenic Traits Source Type: research
Heterotrimeric G protein signaling in polycystic kidney disease
Autosomal dominant polycystic kidney disease (ADPKD) is a signalopathy of renal tubular epithelial cells caused by naturally occurring mutations in two distinct genes, polycystic kidney disease 1 (PKD1) and 2 (PKD2). Genetic variants in PKD1, which encodes the polycystin-1 (PC-1) protein, remain the predominant factor associated with the pathogenesis of nearly two-thirds of all patients diagnosed with PKD. Although the relationship between defective PC-1 with renal cystic disease initiation and progression remains to be fully elucidated, there are numerous clinical studies that have focused upon the control of effector sys...
Source: Physiological Genomics - June 30, 2016 Category: Genetics & Stem Cells Authors: Hama, T., Park, F. Tags: Genetic and Genomics Investigation of Structure and Function of the Kidney Source Type: research
Autocrine effects of transgenic resistin reduce palmitate and glucose oxidation in brown adipose tissue
Resistin has been originally identified as an adipokine that links obesity to insulin resistance in mice. In our previous studies in spontaneously hypertensive rats (SHR) expressing a nonsecreted form of mouse resistin (Retn) transgene specifically in adipose tissue (SHR-Retn), we have observed an increased lipolysis and serum free fatty acids, ectopic fat accumulation in muscles, and insulin resistance. Recently, brown adipose tissue (BAT) has been suggested to play an important role in the pathogenesis of metabolic disturbances. In the current study, we have analyzed autocrine effects of transgenic resistin on BAT glucos...
Source: Physiological Genomics - May 31, 2016 Category: Genetics & Stem Cells Authors: Pravenec, M., Mlejnek, P., Zidek, V., Landa, V., Simakova, M., Silhavy, J., Strnad, H., Eigner, S., Eigner Henke, K., Skop, V., Malinska, H., Trnovska, J., Kazdova, L., Drahota, Z., Mracek, T., Houstek, J. Tags: Genomic and ' Polyomic Studies of Cardiovascular and Inflammatory Diseases Source Type: research
High-resolution mapping of a novel rat blood pressure locus on chromosome 9 to a region containing the Spp2 gene and colocalization of a QTL for bone mass
Through linkage analysis of the Dahl salt-sensitive (S) rat and the spontaneously hypertensive rat (SHR), a blood pressure (BP) quantitative trait locus (QTL) was previously located on rat chromosome 9. Subsequent substitution mapping studies of this QTL revealed multiple BP QTLs within the originally identified logarithm of odds plot by linkage analysis. The focus of this study was on a 14.39 Mb region, the distal portion of which remained unmapped in our previous studies. High-resolution substitution mapping for a BP QTL in the setting of a high-salt diet indicated that an SHR-derived congenic segment of 787.9 kb contain...
Source: Physiological Genomics - May 31, 2016 Category: Genetics & Stem Cells Authors: Nie, Y., Kumarasamy, S., Waghulde, H., Cheng, X., Mell, B., Czernik, P. J., Lecka-Czernik, B., Joe, B. Tags: Genomic and ' Polyomic Studies of Cardiovascular and Inflammatory Diseases Source Type: research
