A5001744349- Hormonal Regulation and Hypertension
- Bioinformatics and Genomic Networks
- Diabetes and associated disorders
- Renin-Angiotensin System Studies
- Birth, Development, and Health
- Biomedical Text Mining and Ontologies
- Sodium Intake and Health
- Pancreatic function and diabetes
- Genetic Associations and Epidemiology
- Blood Pressure and Hypertension Studies
- Immune Cell Function and Interaction
- Genetic Mapping and Diversity in Plants and Animals
- Nitric Oxide and Endothelin Effects
- Gene expression and cancer classification
- Diet, Metabolism, and Disease
- Adipose Tissue and Metabolism
- CRISPR and Genetic Engineering
- Immunodeficiency and Autoimmune Disorders
- Diabetes Management and Research
- Genomics and Phylogenetic Studies
- Metabolomics and Mass Spectrometry Studies
- Animal Genetics and Reproduction
- Molecular Biology Techniques and Applications
- Eicosanoids and Hypertension Pharmacology
- Acute Kidney Injury Research
Medical College of Wisconsin
2012-2025
University of Padua
2023
University at Buffalo, State University of New York
2023
University College London
2023
SIB Swiss Institute of Bioinformatics
2023
Stanford University
2023
Phoenix Bioinformatics
2023
University of Southern California
2023
Children's Hospital of Wisconsin
2010-2018
Pediatrics and Genetics
2014
Abstract The Gene Ontology Consortium (GOC) provides the most comprehensive resource currently available for computable knowledge regarding functions of genes and gene products. Here, we report advances consortium over past two years. new GO-CAM annotation framework was notably improved, formalized model with a computational schema to check validate rapidly increasing repository 2838 GO-CAMs. In addition, describe impacts several collaborations refine GO 10% increase in number annotations,...
Abstract The Rat Genome Database (RGD, https://rgd.mcw.edu) has evolved from simply a resource for rat genetic markers, maps, and genes, by adding multiple genomic data types extensive disease phenotype annotations developing tools to effectively mine, analyze, visualize the available data, empower investigators in their hypothesis-driven research. Leveraging its robust flexible infrastructure, RGD added human eight other model organisms (mouse, 13-lined ground squirrel, chinchilla, naked...
Consomic rats (SS.BN13), in which chromosome 13 from normotensive inbred Brown Norway a colony maintained at the Medical College of Wisconsin (BN/Mcw) was introgressed into background Dahl salt-sensitive (SS/Mcw) rats, also Wisconsin, were bred. The present studies determined mean arterial pressure (MAP) responses to salt and renal peripheral vascular norepinephrine angiotensin II; 24-hour protein excretion histological analyses used assess pathology that received high (4% NaCl) diet for 4...
Formed in late 1999, the Rat Genome Database (RGD, https://rgd.mcw.edu) will be 20 2020, Year of Rat. Because laboratory rat, Rattus norvegicus, has been used as a model for complex human diseases such cardiovascular disease, diabetes, cancer, neurological disorders and arthritis, among others, >150 years, RGD always disease-focused committed to providing data tools researchers doing comparative genomics translational studies. At its inception, before sequencing rat genome, started with only...
With the draft sequence of human genome available, there is a need to better define gene function in context systems biology. We studied 239 cardiovascular and renal phenotypes 113 male rats derived from an F 2 intercross mapped 81 these traits onto genome. Aggregates were identified on chromosomes 1, 2, 7, 18. Systems biology was assessed by examining patterns correlations (“physiological profiles”) that can be used for hunting, mechanism-based physiological studies, and, with comparative...
The present study evaluated the role of endogenous P-450 metabolites arachidonic acid (AA) on autoregulation renal blood flow in rats. Whole kidney and cortical flows were well autoregulated when perfusion pressure was varied from 150 to 100 mmHg. Infusion 17-octadecynoic (17-ODYA) into artery (33 nmol/min) increased papillary by 12.6 +/- 2.5 26.5 4.6%, respectively. After 17-ODYA, whole impaired. Intrarenal infusion miconazole (8 had no effect kidney, cortical, or flows. 17-ODYA (1 microM)...
This study examines the nephron segments contributing to blunted pressure-natriuretic response in Dahl salt-sensitive rats. Urine and late proximal early distal tubular fluid samples were collected from 16-20-week-old, inbred (DS/Jr) salt-resistant (DR/Jr) rats, (DS) (DR) rats Brookhaven colony, that maintained birth on a low (0.3%) sodium chloride diet. flow excretions 65% less DS/Jr than DR/Jr when their kidneys perfused at an equal renal perfusion pressure of approximately 150 mm Hg. The...
The purpose of the present study was to evaluate relationship aldosterone blood pressure and left ventricular size in black American (n=109) white French Canadian (n=73) patients with essential hypertension. Measurements were obtained off antihypertensive medications included 24-hour monitoring, plasma renin activity aldosterone, an echocardiogram. Compared Canadians, Americans had higher body mass indexes, systolic pressures, attenuated nighttime reduction pressure, lower serum potassium...
Genetic linkage analyses in human populations have traditionally combined male and female progeny for determination of quantitative trait loci (QTL). In contrast, most rodent studies focused primarily on males. This study represents an extensive female-specific analysis which 236 neuroendocrine, renal, cardiovascular traits related to arterial pressure (BP) were determined 99 F2 rats derived from a cross Dahl salt-sensitive SS/JrHsdMcwi (SS) Brown Norway normotensive BN/SsNHsdMcwi (BN) rats....
Renal injury in the Dahl salt-sensitive rat mimics human forms of hypertension that are particularly prevalent black individuals, but mechanisms lead to development this incompletely understood. We studied impact renal perfusion pressure (RPP) on model. During salt-induced over 2 wk, RPP left kidney was maintained at control levels (125 +/- mmHg) by continuous servocontrol inflation an aortic balloon implanted between arteries; during same period, right rose 164 8 mmHg. After wk a 4% salt...
The influence of kinins and angiotensin II on the regulation renal cortical papillary blood flow sodium water excretion was examined in rats. Superficial flows were measured using a laser-Doppler flowmeter. Papillary increased 50% after enalaprilat (60 micrograms/kg) phosphoramidon (5.5 micrograms.kg-1.min-1) given along with 0.3 M bicarbonate solution to inhibit degradation enhance urinary kallikrein activity. Infusion kinin antagonist, D-Arg-Hyp-Thi-D-Phe-bradykinin (5 micrograms/min),...
Previous studies have indicated that substitution of chromosome 13 the salt-resistant Brown Norway BN/SsNHsdMcwi (BN) rat into genomic background Dahl salt-sensitive SS/JrHsdMcwi (SS) attenuates development hypertension and renal damage. To identify regions within attenuate during a high-salt diet in SS rat, we phenotyped series overlapping congenic lines covering 13, generated from an intercross between consomic SS-13 BN rat. Blood pressure was determined chronically catheterized rats after...
Mechanisms associated with type 1 diabetes (T1D) development remain incompletely defined. Using a sensitive array-based bioassay where patient plasma is used to induce transcriptional responses in healthy leukocytes, we previously reported disease-specific, partially interleukin (IL)-1−dependent signatures preonset and recent onset (RO) T1D relative unrelated control subjects (uHC). To better understand inherited susceptibility families, conducted cross-sectional longitudinal analyses of...
It was hypothesized that IL-1 antagonism would preserve β-cell function in new onset Type 1 diabetes (T1D). However, the Anti-Interleukin-1 Diabetes Action (AIDA) and TrialNet Canakinumab (TN-14) trials failed to show efficacy of receptor antagonist (IL-1Ra) or canakinumab, as measured by stimulated C-peptide response. Additional measures are needed define immune state changes associated with therapeutic responses. Here, we studied these trial participants plasma-induced transcriptional...
Our long-term objective is to identify genes whose expression results in hypertension and phenotypic changes that may contribute hypertension. The purpose of the present study was describe evidence for heritability hypertension-related phenotypes hypertensive, hyperlipidemic black sib pairs. Outpatient anthropomorphic measurements were obtained >200 affected In addition, 68 these pairs studied under controlled, standardized conditions at an inpatient clinical research center while off both...
Single-channel K+ currents were characterized in vascular smooth muscle cells freshly isolated from preglomerular arterioles (15–40 microns OD) of the rat. Under conditions symmetrical (145 mM), two types single-channel with unitary slope conductances 68 +/- 2.6 and 251 4.9 pS recorded excised inside-out membrane patches. The open state probability (NPo) these channels was voltage sensitive highly selective for over Na+. Elevation intracellular calcium concentration ([Ca2+]i) 0.1 to 0.5...
The purpose of this study is to evaluate the relationship between aldosterone and blood pressure in a total 220 normotensive 293 essential hypertensive subjects 2 genetically distinct populations-blacks white French Canadians. 24-hour monitoring was performed under standardized conditions after discontinuing antihypertensive medications. Plasma renin activity plasma were measured supine position standing for 10 minutes. atrial natriuretic factor also measured. Supine activities lower (P< or...
The present study examined whether an alteration in renal medullary hemodynamics is associated with the development of hypertension spontaneously hypertensive rat (SHR). relationships between whole kidney, cortical and papillary blood flows, perfusion pressure were compared 3- to 5-, 6- 9-, 12- 16-week-old SHR Wistar-Kyoto rats (WKY). Cortical flows similar different age groups WKY over most range studied. Control determined at a equal mean arterial each animal, not significantly 5-...
Experiments examined the influence of diet and genetics on hypertension renal disease in inbred Dahl salt-sensitive (SS/Mcw) rats consomic which chromosomes 16 (SS.BN16) or 18 (SS.BN18) normotensive Brown Norway rat were inserted into genetic background SS/Mcw. SS/Mcw breeders offspring randomly placed a purified AIN-76A grain-based diet, male screened for cardiovascular phenotypes following 3 wk 4.0% NaCl diet. High-salt arterial blood pressure (162 ± 5 mmHg, n = 10), urinary protein...
Hypertension is associated with increased levels of oxidative stress and medullary renal injury. Previous studies have shown that elevations in perfusion pressure increase Na + delivery to the thick ascending limb (mTAL), enhancement NaCl transport outer medulla has been reported many experimental forms hypertension. This study examined effects fluid mTAL perfused vitro on generation superoxide. Osmolality was maintained constant between low- high-Na perfusates by adjusting choline Cl − ....
Abstract The genetic basis of type 2 diabetes remains incompletely defined despite the use multiple strategies. Multiparental populations such as heterogeneous stocks (HS) facilitate gene discovery by allowing fine mapping to only a few megabases, significantly decreasing number potential candidate genes compared traditional In present work, we employed expression and sequence analysis in HS rats (Rattus norvegicus) identify Tpcn2 likely causal underlying 3.1-Mb locus for glucose insulin...
Abstract The Rat Genome Database (RGD) is a multispecies knowledgebase which integrates genetic, multiomic, phenotypic, and disease data across 10 mammalian species. To support cross-species, multiomics studies to enhance expand on manually extracted from the biomedical literature by RGD team of expert curators, imports multiple sources. These include major databases substantial number domain-specific resources, as well direct submissions individual researchers. incorporation these diverse...