188 research outputs found

    Nephrocystin-1 Forms a Complex with Polycystin-1 via a Polyproline Motif/SH3 Domain Interaction and Regulates the Apoptotic Response in Mammals

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    Mutations in PKD1, the gene encoding for the receptor Polycystin-1 (PC-1), cause autosomal dominant polycystic kidney disease (ADPKD). The cytoplasmic C-terminus of PC-1 contains a coiled-coil domain that mediates an interaction with the PKD2 gene product, Polycystin-2 (PC-2). Here we identify a novel domain in the PC-1 C-terminal tail, a polyproline motif mediating an interaction with Src homology domain 3 (SH3). A screen for interactions using the PC-1 C-terminal tail identified the SH3 domain of nephrocystin-1 (NPHP1) as a potential binding partner of PC-1. NPHP1 is the product of a gene that is mutated in a different form of renal cystic disease, nephronophthisis (NPHP). We show that in vitro pull-down assays and NMR structural studies confirmed the interaction between the PC-1 polyproline motif and the NPHP1 SH3 domain. Furthermore, the two full-length proteins interact through these domains; using a recently generated model system allowing us to track endogenous PC-1, we confirm the interaction between the endogenous proteins. Finally, we show that NPHP1 trafficking to cilia does not require PC-1 and that PC-1 may require NPHP1 to regulate resistance to apoptosis, but not to regulate cell cycle progression. In line with this, we find high levels of apoptosis in renal specimens of NPHP patients. Our data uncover a link between two different ciliopathies, ADPKD and NPHP, supporting the notion that common pathogenetic defects, possibly involving de-regulated apoptosis, underlie renal cyst formation. © 2010 Wodarczyk et al

    View From the Inside: Older Adults

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    M. Wodarczyk, Capt. H.D. Campbell, Capt. R.A. Presley, Maj. E. Ross Rowell

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    Title from unverified data provided by the Bain News Service on the negatives or caption cards.Forms part of: George Grantham Bain Collection (Library of Congress).General information about the Bain Collection is available at http://hdl.loc.gov/loc.pnp/pp.ggbai

    RADIO FREQUENCY--MICROWAVE DOUBLE RESONANCE AS A TOOL IN THE ANALYSIS OF MICROWAVE SPECTRA

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    This work was supported by the National Science Foundation. 1^{1}S. H. Autler and C. H. Townes, Phys. Rev. 100, 703 (1955).""Author Institution: Department of Chemistry, Harvard University,The practical application of radio frequency-microwave double resonance1resonance^{1} (RFMDR) as a spectroscopic technique in the analysis of microwave spectra has been investigated. A high-power amplitude-modulated radio-frequency field applied to the Stark septum of a conventional waveguide provides a means of detecting microwave transitions, analogous to the situation in microwave-microwave double resonance (MMDR). The sensitivity of the technique compares favorably with that of MMDR and Stark modulation. Nearly prolate asymmetric top molecules with allowed a-type transitions are especially amenable to the technique due to the presence of favorable radio-frequency transitions between asymmetry doublets. Accidental near degeneracies of dipole-connected rotational levels are also useful. A description of a RFMDR spectrometer using conventional as well as slightly modified Stark cell waveguides will be presented. Limitations and special problems posed by the nature of radio-frequency circuits will be discussed, and examples of applications together with suggestions for other possible uses will be given

    Study of D*(2010)+- Production in ep Collisions at HERA

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    We report the first observation of charmed mesons with the ZEUS detector at HERA using the decay channel D*+ → (D0 → K-π+)π+ (+c.c.). Clear signals in the mass difference ΔM=M(D*)-M(D0) as well as in the M (Kπ) distribution at the D0 mass are found. The ep cross section for inclusive D*± production with Q2 < 4 GeV2 in the γp centre-of-mass energy range 115 < W < 275 GeV has been determined to be (32±7-7+4)nb m the kinematic region {pT(D*) ≥ 1.7 GeV, |η(D*)| < 1-5}. Extrapolating outside this region, assuming a mass of the charm quark of 1.5 GeV, we estimate the ep charm cross section to be σ(ep → cc̄Χ) = (0.45 ± 0.11-0.22+0.37) μb at √s = 296 GeV and 〈W〉 = 198 GeV. The average γp charm cross section σ(γp → cc̄Χ) is found to be (6.3 ± 2.2-3.0+6.3) μb at 〈W〉 = 163 GeV and (16.9 ± 5.2-8.5+13.9) μb at 〈W〉 = 243 GeV. The increase of the total charm photoproduction cross section by one order of magnitude with respect to low energy data experiments is well described by QCD NLO calculations using singular gluon distributions in the proton

    Measurement of dijet production in neutral current deep inelastic scattering at high Q(2) and determination of alpha(s)

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    Dijet production has been studied in neutral current deep inelastic e(+)p scattering for 470 lt Q(2) lt 20000 GeV2 with the ZEUS detector at HERA using an integrated luminosity of 38.4 pb(-1). Dijet differential cross sections are presented in a kinematic region where both theoretical and experimental uncertainties are small. Next-to-leading-order (NLO) QCD calculations describe the measured differential cross sections well. A QCD analysis of the measured dijet fraction as a function of Q(2) allows both a precise determination of alpha (s)(M-z) and a test of the energy-scale dependence of the strong coupling constant. A detailed analysis provides an improved estimate of the uncertainties of the NLO QCD cross sections arising from the parton distribution functions of the proton. The value of cu,(Mz), as determined from the QCD fit, is alpha (s)(M-z) = 0.1166 +/- 0.0019(stat.)(- 0.0033)(+0.0024)(exp.)(-0.0044)(+0.0057)(th.)
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