457 research outputs found

    DNA insertions distinguish the duplicated renin genes of DBA/2 and M. hortulanus mice

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    In a survey of inbred and wild mouse DNAs for genetic variation at the duplicate renin loci, Ren-1 and Ren-2 , a variant Not I hybridization pattern was observed in the wild mouse M. hortulanus . To determine the basis for this variation, the structure of the M. hortulanus renin loci has been examined in detail and compared to that of the inbred strain DBA/2. Overall, the gross features of structure in this chromosomal region are conserved in both Mus species. In particular, the sequence at the recombination site between the linked Ren-1 and Ren-2 loci was found to be identical in both DBA/2 and M. hortulanus , indicating that the renin gene duplication occurred prior to the divergence of ancestors of these mice. Renin flanking sequences in M. hortulanus , however, were found to lack four DNA insertions totaling approximately 10.5 kb which reside near the DBA/2 loci. The postduplication evolution of the mouse renin genes in thus characterized by a number of insertion and/or deletion events within nearby flanking sequences. Analysis of renin expression showed little or no difference between these mice in steady state renin RNA levels in most tissues examined, suggesting that these insertions do not influence expression at those sites. A notable exception is the adrenal gland, in which DBA/2 and M. hortulanus mice exhibit different patterns of developmentally regulated renin expression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46988/1/335_2004_Article_BF00570438.pd

    Identification of a human ortholog of the mouse Dcpp gene locus, encoding a novel member of the CSP-1/Dcpp salivary protein family

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    Glycolaldehyde is a key molecule in the formation of biologically relevant molecules such as ribose. We report its detection with the Plateau de Bure interferometer towards the Class 0 young stellar object NGC1333 IRAS2A, which is only the second solar-type protostar for which this prebiotic molecule is detected. Local thermodynamic equilibrium analyses of glycolaldehyde, ethylene glycol (the reduced alcohol of glycolaldehyde) and methyl formate (the most abundant isomer of glycolaldehyde) were carried out. The relative abundance of ethylene glycol to glycolaldehyde is found to be ~5 -higher than in the Class 0 source IRAS 16293-2422 (~1), but comparable to the lower limits derived in comets (\geq3-6). The different ethylene glycol-to-glycolaldehyde ratios in the two protostars could be related to different CH3OH:CO compositions of the icy grain mantles. In particular, a more efficient hydrogenation on the grains in NGC 1333 IRAS2A would favor the formation of both methanol and ethylene glycol. In conclusion, it is possible that, like NGC 1333 IRAS2A, other low-mass protostars show high ethylene glycol-to-glycolaldehyde abundance ratios. The cometary ratios could consequently be inherited from earlier stages of star formation, if the young Sun experienced conditions similar to NGC1333 IRAS2A.Comment: 11 pages, 5 figures, accepted in A&

    Tuberous sclerosis complex exhibits a new renal cystogenic mechanism

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    Tuberous sclerosis complex (TSC) is a tumor predisposition syndrome with significant renal cystic and solid tumor disease. While the most common renal tumor in TSC, the angiomyolipoma, exhibits a loss of heterozygosity associated with disease, we have discovered that the renal cystic epithelium is composed of type A intercalated cells that have an intact Tsc gene that have been induced to exhibit Tsc‐mutant disease phenotype. This mechanism appears to be different than that for ADPKD. The murine models described here closely resemble the human disease and both appear to be mTORC1 inhibitor responsive. The induction signaling driving cystogenesis may be mediated by extracellular vesicle trafficking.TSC renal cystic disease develops in about half of the patients. The disease appears to caused by an induction mechanism such that a small population of mutant cells can cause significant renal cystic disease comprised of mostly genetically normal cells.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147796/1/phy213983.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147796/2/phy213983_am.pd

    Bimodal dynamics of granular organelles in primary renin-expressing cells revealed using TIRF microscopy

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    Renin is the initiator and rate-limiting factor in the renin-angiotensin blood pressure regulation system. Although renin is not exclusively produced in the kidney, in nonmurine species the synthesis and secretion of the active circulatory enzyme is confined almost exclusively to the dense core granules of juxtaglomerular (JG) cells, where prorenin is processed and stored for release via a regulated pathway. Despite its importance, the structural organization and regulation of granules within these cells is not well understood, in part due to the difficulty in culturing primary JG cells in vitro and the lack of appropriate cell lines. We have streamlined the isolation and culture of primary renin-expressing cells suitable for high-speed, high-resolution live imaging using a Percoll gradient-based procedure to purify cells from RenGFP+ transgenic mice. Fibronectin-coated glass coverslips proved optimal for the adhesion of renin-expressing cells and facilitated live cell imaging at the plasma membrane of primary renin cells using total internal reflection fluorescence microscopy (TIRFM). To obtain quantitative data on intracellular function, we stained mixed granule and lysosome populations with Lysotracker Red and stimulated cells using 100 nM isoproterenol. Analysis of membrane-proximal acidic granular organelle dynamics and behavior within renin-expressing cells revealed the existence of two populations of granular organelles with distinct functional responses following isoproterenol stimulation. The application of high-resolution techniques for imaging JG and other specialized kidney cells provides new opportunities for investigating renal cell biology

    Colour reconnection in e+e- -> W+W- at sqrt(s) = 189 - 209 GeV

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    The effects of the final state interaction phenomenon known as colour reconnection are investigated at centre-of-mass energies in the range sqrt(s) ~ 189-209 GeV using the OPAL detector at LEP. Colour reconnection is expected to affect observables based on charged particles in hadronic decays of W+W-. Measurements of inclusive charged particle multiplicities, and of their angular distribution with respect to the four jet axes of the events, are used to test models of colour reconnection. The data are found to exclude extreme scenarios of the Sjostrand-Khoze Type I (SK-I) model and are compatible with other models, both with and without colour reconnection effects. In the context of the SK-I model, the best agreement with data is obtained for a reconnection probability of 37%. Assuming no colour reconnection, the charged particle multiplicity in hadronically decaying W bosons is measured to be (nqqch) = 19.38+-0.05(stat.)+-0.08 (syst.).Comment: 30 pages, 9 figures, Submitted to Euro. Phys. J.

    Search for the Standard Model Higgs Boson with the OPAL Detector at LEP

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    This paper summarises the search for the Standard Model Higgs boson in e+e- collisions at centre-of-mass energies up to 209 GeV performed by the OPAL Collaboration at LEP. The consistency of the data with the background hypothesis and various Higgs boson mass hypotheses is examined. No indication of a signal is found in the data and a lower bound of 112.7GeV/C^2 is obtained on the mass of the Standard Model Higgs boson at the 95% CL.Comment: 51 pages, 21 figure
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