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  • 1
    Publication Date: 2001-11-27
    Description: With the draft sequence of the human genome available, there is a need to better define gene function in the context of systems biology. We studied 239 cardiovascular and renal phenotypes in 113 male rats derived from an F2 intercross and mapped 81 of these traits onto the genome. Aggregates of traits were identified on chromosomes 1, 2, 7, and 18. Systems biology was assessed by examining patterns of correlations ("physiological profiles") that can be used for gene hunting, mechanism-based physiological studies, and, with comparative genomics, translating these data to the human genome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stoll, M -- Cowley, A W Jr -- Tonellato, P J -- Greene, A S -- Kaldunski, M L -- Roman, R J -- Dumas, P -- Schork, N J -- Wang, Z -- Jacob, H J -- 1P50-HL-54998/HL/NHLBI NIH HHS/ -- R01 HL064541/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2001 Nov 23;294(5547):1723-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Bioinformatics Research Center, and, Human and Molecular Genetics Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226-0509, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11721057" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Pressure/drug effects/genetics ; *Cardiovascular Physiological Phenomena/drug effects ; Chromosome Mapping/*methods ; Chromosomes/genetics ; Crosses, Genetic ; Female ; Genomics/*methods ; Humans ; Kidney/physiology ; Lod Score ; Male ; Nitric Oxide Synthase/genetics ; Norepinephrine/pharmacology ; Phenotype ; Quantitative Trait, Heritable ; Rats ; Vasodilation/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 26 (1998), S. 911-913 
    ISSN: 1573-9686
    Keywords: Physiological database ; Mathematical model ; Physiome: microcirculation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Presented is a discussion of steps towards the creation of a database of the microcirculation encompassing anatomical and functional experimental data, and conceptual and computational models. The discussion includes issues of database utility, organization, data deposition, and linkage to other databases. The database will span levels from gene to tissue and will serve both research and educational purposes. © 1998 Biomedical Engineering Society. PAC98: 8745Ft, 8710+e, 0130Cc
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2006-10-01
    Print ISSN: 1535-3893
    Electronic ISSN: 1535-3907
    Topics: Chemistry and Pharmacology
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  • 4
    Publication Date: 2014-12-20
    Description: Motivation: RNA-Seq (also called whole-transcriptome sequencing) is an emerging technology that uses the capabilities of next-generation sequencing to detect and quantify entire transcripts. One of its important applications is the improvement of existing genome annotations. RNA-Seq provides rapid, comprehensive and cost-effective tools for the discovery of novel genes and transcripts compared with expressed sequence tag (EST), which is instrumental in gene discovery and gene sequence determination. The rat is widely used as a laboratory disease model, but has a less well-annotated genome as compared with humans and mice. In this study, we incorporated deep RNA-Seq data from three rat tissues—bone marrow, brain and kidney—with EST data to improve the annotation of the rat genome. Results: Our analysis identified 32 197 transcripts, including 13 461 known transcripts, 13 934 novel isoforms and 4802 new genes, which almost doubled the numbers of transcripts in the current public rat genome database (rn5). Comparisons of our predicted protein-coding gene sets with those in public datasets suggest that RNA-Seq significantly improves genome annotation and identifies novel genes and isoforms in the rat. Importantly, the large majority of novel genes and isoforms are supported by direct evidence of RNA-Seq experiments. These predicted genes were integrated into the Rat Genome Database (RGD) and can serve as an important resource for functional studies in the research community. Availability and implementation: The predicted genes are available at http://rgd.mcw.edu . Contact: hmxu@zju.edu.cn or pliu@mcw.edu or yanlu76@zju.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 5
    Publication Date: 2005-07-01
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 6
    Publication Date: 2019-07-13
    Description: Only functional studies have suggested the presence of the ANG II type 2 (AT2) receptor in the microcirculation. To determine the distribution of this receptor in the rat skeletal muscle microcirculation, a polyclonal rabbit anti-rat antiserum was developed and used for immunohistochemistry and Western blot analysis. The antiserum was prepared against a highly specific and antigenic AT2-receptor synthetic peptide and was validated by competition and sensitivity assays. Western blot analysis demonstrated a prominent, single band at approximately 40 kDa in cremaster and soleus muscle. Immunohistochemical analysis revealed a wide distribution of AT2 receptors throughout the skeletal muscle microcirculation in large and small microvessels. Microanatomic studies displayed an endothelial localization of the AT2 receptor, whereas dual labeling with smooth muscle alpha-actin also showed colocalization of the AT2 receptor with vascular smooth muscle cells. Other cells associated with the microvessels also stained positive for AT2 receptors. Briefly, this study confirms previous functional data and localizes the AT2 receptor to the microcirculation. These studies demonstrate that the AT2 receptor is present on a variety of vascular cell types and that it is situated in a fashion that would allow it to directly oppose ANG II type 1 receptor actions.
    Keywords: Life Sciences (General)
    Type: The American journal of physiology (ISSN 0002-9513); 275; 4 Pt 2; H1395-403
    Format: text
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  • 7
    Publication Date: 2019-07-13
    Description: OBJECTIVE: Angiotensin II (ANGII) plays a critical role in the maintenance of the microcirculation and in the anatomical loss of microvessels (rarefaction) that occurs in low renin forms of hypertension and in animals fed a high-salt diet. Elevations in sodium intake can trigger a series of hemodynamic and hormonal responses culminating in a substantial rarefaction of small arterioles and capillaries in both normal and reduced renal mass hypertensive rats. METHODS: Immunohistochemistry, Northern blot, and reverse transcription-polymerase chain reaction (RT-PCR) analysis of microdissected blood vessels were used to localize ANGII receptors in the microcirculation. Chronic infusion of ANGII and other physiologic and pharmacologic manipulations of the reninangiotensin system in rats was combined with morphologic and mathematical analysis of the network architecture. RESULTS: We have shown that rarefaction of the microcirculation can cause an increase in total peripheral resistance, reduced tissue perfusion, decreased oxygen delivery, and impaired organ function. Although the mechanisms by which this occurs are not well understood, a number of key observations point to a role for the renin-angiotensin system in this effect. First, ANGII infused systemically at subpressor levels, or locally into the skeletal muscle interstitium, can induce significant microvessel growth. Second, localization of ANGII receptor proteins by immunohistochemistry and Western blotting and RNA localization by RT-PCR confirm the presence of AT1 receptors, which are growth-stimulatory, and AT2 receptors, which are growth-inhibitory in the microcirculation. Third, maintenance of ANGII at normal levels during periods of hypertension or high-salt diet completely eliminates rarefaction. CONCLUSIONS: Taken together, these results support the hypothesis that ANGII acting through AT1- and AT2-receptor mechanisms modulate vessel density during high-salt diet and hypertension.
    Keywords: Life Sciences (General)
    Type: Microcirculation (New York, N.Y. : 1994) (ISSN 1073-9688); 5; 3-Feb; 101-7
    Format: text
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  • 8
    Publication Date: 2019-07-13
    Description: Angiotensin II decreases glomerular filtration rate, renal plasma flow, and glomerular capillary hydraulic conductivity. Although angiotensin II receptors have been demonstrated in mesangial cells and proximal tubule cells, the presence of angiotensin II receptors in glomerular epithelial cells has not previously been shown. Previously, we have reported that angiotensin II caused an accumulation of cAMP and a reorganization of the actin cytoskeleton in cultured glomerular epithelial cells. Current studies were conducted to verify the presence of angiotensin II receptors by immunological and non-peptide receptor ligand binding techniques and to ascertain the activation of intracellular signal transduction in glomerular epithelial cells in response to angiotensin II. Confluent monolayer cultures of glomerular epithelial cells were incubated with angiotensin II, with or without losartan and/or PD-123,319 in the medium. Membrane vesicle preparations were obtained by homogenization of washed cells followed by centrifugation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membrane proteins followed by multiscreen immunoblotting was used to determine the presence of angiotensin II receptor type 1 (AT1) or type 2 (AT2). Angiotensin II-mediated signal transduction in glomerular epithelial cells was studied by measuring the levels of cAMP, using radioimmunoassay. Results obtained in these experiments showed the presence of both AT1 and AT2 receptor types in glomerular epithelial cells. Angiotensin II was found to cause an accumulation of cAMP in glomerular epithelial cells, which could be prevented only by simultaneous use of losartan and PD-123,319, antagonists for AT1 and AT2, respectively. The presence of both AT1 and AT2 receptors and an increase in cAMP indicate that glomerular epithelial cells respond to angiotensin II in a manner distinct from that of mesangial cells or proximal tubular epithelial cells. Our results suggest that glomerular epithelial cells participate in angiotensin II-mediated control of the glomerular filtration barrier.
    Keywords: Life Sciences (General)
    Type: The American journal of physiology (ISSN 0002-9513); 274; 3 Pt 2; F623-7
    Format: text
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