| 1. |
- Aamodt, K., et al.
(författare)
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The ALICE experiment at the CERN LHC
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08002
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Forskningsöversikt (refereegranskat)abstract
- ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
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| 2. |
- Adare, A., et al.
(författare)
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Photon-hadron jet correlations in p plus p and Au plus Au collisions at s(NN)=200 GeV
- 2009
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 80:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the observation at the Relativistic Heavy Ion Collider of suppression of back-to-back correlations in the direct photon+jet channel in Au+Au relative to p+p collisions. Two-particle correlations of direct photon triggers with associated hadrons are obtained by statistical subtraction of the decay photon-hadron (gamma-h) background. The initial momentum of the away-side parton is tightly constrained, because the parton-photon pair exactly balance in momentum at leading order in perturbative quantum chromodynamics, making such correlations a powerful probe of the in-medium parton energy loss. The away-side nuclear suppression factor, I-AA, in central Au+Au collisions, is 0.32 +/- 0.12(stat)+/- 0.09(syst) for hadrons of 3 < p(T)(h)< 5 in coincidence with photons of 5 < p(T)(gamma)< 15 GeV/c. The suppression is comparable to that observed for high-p(T) single hadrons and dihadrons. The direct photon associated yields in p+p collisions scale approximately with the momentum balance, z(T)equivalent to p(T)(h)/p(T)(gamma), as expected for a measurement of the away-side parton fragmentation function. We compare to Au+Au collisions for which the momentum balance dependence of the nuclear modification should be sensitive to the path-length dependence of parton energy loss.
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| 3. |
- Adare, A., et al.
(författare)
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Measurement of Bottom Versus Charm as a Function of Transverse Momentum with Electron-Hadron Correlations in p plus p Collisions at s=200 GeV
- 2009
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Ingår i: Physical Review Letters. - 1079-7114. ; 103:8
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Tidskriftsartikel (refereegranskat)abstract
- The momentum distribution of electrons from semileptonic decays of charm and bottom quarks for midrapidity |y|< 0.35 in p+p collisions at s=200 GeV is measured by the PHENIX experiment at the Relativistic Heavy Ion Collider over the transverse momentum range 2 < p(T)< 7 GeV/c. The ratio of the yield of electrons from bottom to that from charm is presented. The ratio is determined using partial D/D -> e(+/-)K(-/+)X (K unidentified) reconstruction. It is found that the yield of electrons from bottom becomes significant above 4 GeV/c in p(T). A fixed-order-plus-next-to-leading-log perturbative quantum chromodynamics calculation agrees with the data within the theoretical and experimental uncertainties. The extracted total bottom production cross section at this energy is sigma(bb)=3.2(-1.1)(+1.2)(stat)(-1.3)(+1.4)(syst)mu b.
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| 4. |
- Adare, A., et al.
(författare)
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Onset of pi(0) Suppression Studied in Cu plus Cu Collisions at root s(NN)=22.4, 62.4, and 200 GeV
- 2008
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Ingår i: Physical Review Letters. - 1079-7114. ; 101:16
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Tidskriftsartikel (refereegranskat)abstract
- Neutral pion transverse momentum (p(T)) spectra at midrapidity (|y| less than or similar to 0.35) were measured in Cu + Cu collisions at root s(NN) = 22.4, 62.4, and 200 GeV. Relative to pi(0) yields in p + p collisions scaled by the number of inelastic nucleon-nucleon collisions (N-coll) the pi(0) yields for p(T) greater than or similar to 2 GeV/c in central Cu + Cu collisions are suppressed at 62.4 and 200 GeV whereas an enhancement is observed at 22.4 GeV. A comparison with a jet-quenching model suggests that final state parton energy loss dominates in central Cu + Cu collisions at 62.4 and 200 GeV, while the enhancement at 22.4 GeV is consistent with nuclear modifications in the initial state alone.
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| 5. |
- Adare, A., et al.
(författare)
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Gluon-Spin Contribution to the Proton Spin from the Double-Helicity Asymmetry in Inclusive pi(0) Production in Polarized p plus p Collisions at root s=200 GeV
- 2009
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Ingår i: Physical Review Letters. - 1079-7114. ; 103:1
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Tidskriftsartikel (refereegranskat)abstract
- The double helicity asymmetry in neutral pion production for p(T) = 1 to 12 GeV/c was measured with the PHENIX experiment to access the gluon-spin contribution, Delta G, to the proton spin. Measured asymmetries are consistent with zero, and at a theory scale of mu 2 = 4 GeV2 a next to leading order QCD analysis gives Delta G([0.02,0.3]) = 0.2, with a constraint of -0.7 < Delta G([0.02,0.3]) < 0.5 at Delta chi(2) = 9 (similar to 3 sigma) for the sampled gluon momentum fraction (x) range, 0.02 to 0.3. The results are obtained using predictions for the measured asymmetries generated from four representative fits to polarized deep inelastic scattering data. We also consider the dependence of the Delta G constraint on the choice of the theoretical scale, a dominant uncertainty in these predictions.
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| 6. |
- Adare, A., et al.
(författare)
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Inclusive cross section and double helicity asymmetry for pi(0) production in p plus p collisions at root s=62.4 GeV
- 2009
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 79:1
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX experiment presents results from the RHIC 2006 run with polarized p + p collisions at root s = 62.4 GeV, for inclusive pi(0) production at midrapidity. Unpolarized cross section results are measured for transverse momenta p(T) = 0.5 to 7 GeV/c. Next-to-leading order perturbative quantum chromodynamics calculations are compared with the data, and while the calculations are consistent with the measurements, next-to-leading logarithmic corrections improve the agreement. Double helicity asymmetries A(LL) are presented for p(T) = 1 to 4 GeV/c and probe the higher range of Bjorken x of the gluon (x(g)) with better statistical precision than our previous measurements at root s = 200 GeV. These measurements are sensitive to the gluon polarization in the proton for 0.06 < x(g) < 0.4.
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| 7. |
- Abbondanno, U, et al.
(författare)
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The data acquisition system of the neutron time-of-flight facility n_TOF at CERN
- 2005
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 538:1-3, s. 692-702
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Tidskriftsartikel (refereegranskat)abstract
- The n_TOF facility at CERN has been designed for the measurement of neutron capture, fission and (n, xn) cross-sections with high accuracy. This requires a flexible and-due to the high instantaneous neutron flux-almost dead time free data acquisition system. A scalable and versatile data solution has been designed based on 8-bit flash-ADCs with sampling rates up to 2 GHz and 8 Mbyte memory buffer. The software is written in C and C++ and is running on PCs equipped with RedHat Linux.
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| 8. |
- Aggarwal, M. M., et al.
(författare)
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Suppression of high-p(T) neutral pion production in central Pb+Pb collisions at root s(NN)=17.3 GeV relative to p+C and p+Pb collisions
- 2008
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Ingår i: Physical Review Letters. - 1079-7114. ; 100:24
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Tidskriftsartikel (refereegranskat)abstract
- Neutral pion transverse momentum spectra were measured in p+C and p+Pb collisions at root s(NN) = 17.4 GeV at midrapidity (2.3 less than or similar to eta(lab)less than or similar to 3.0) over the range 0.7 less than or similar to p(T)less than or similar to 3.5 GeV/c. The spectra are compared to pi(0) spectra measured in Pb+Pb collisions at root s(NN) = 17.3 GeV in the same experiment. For a wide range of Pb+Pb centralities (N-part less than or similar to 300), the yield of pi(0)'s with p(T)greater than or similar to 2 GeV/c is larger than or consistent with the p+C or p+Pb yields scaled with the number of nucleon-nucleon collisions (N-coll), while for central Pb+Pb collisions with N-part greater than or similar to 350, the pi(0) yield is suppressed.
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| 9. |
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| 10. |
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| 11. |
- Siegert, P., et al.
(författare)
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Exchanging the substrate specificities of pyruvate decarboxylase from Zymomonas mobilis and benzoylformate decarboxylase from Pseudomonas putida
- 2005
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Ingår i: Protein Engineering Design & Selection. - : Oxford University Press (OUP). - 1741-0126 .- 1741-0134. ; 18:7, s. 345-357
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Tidskriftsartikel (refereegranskat)abstract
- Pyruvate decarboxylase from Zymomonas mobilis (PDC) and benzoylformate decarboxylase from Pseudomonas putida (BFD) are thiamine diphosphate-dependent enzymes that decarboxylate 2-keto acids. Although they share a common homotetrameric structure they have relatively low sequence similarity and different substrate spectra. PDC prefers short aliphatic substrates whereas BFD favours aromatic 2-keto acids. These preferences are also reflected in their carboligation reactions. PDC catalyses the conversion of benzaldehyde and acetaldehyde to (R)-phenylacetylcarbinol and predominantly (S)-acetoin, whereas (R)-benzoin and mainly (S)-2-hydroxypropiophenone are the products of BFD catalysis. Comparison of the X-ray structures of both enzymes identified two residues in each that were likely to be involved in determining substrate specificity. Site-directed mutagenesis was used to interchange these residues in both BFD and PDC. The substrate range and kinetic parameters for the decarboxylation reaction were studied for each variant. The most successful variants, PDCI472A and BFDA460I, catalysed the decarboxylation of benzoylformate and pyruvate, respectively, although both variants now preferred the long-chain aliphatic substrates, 2-ketopentanoic and 2-ketohexanoic acid. With respect to the carboligase activity, PDCI472A proved to be a real chimera between PDC and BFD whereas BFDA460I/F464I provided the most interesting result with an almost complete reversal of the stereochemistry of its 2-hydroxypropiophenone product.
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| 12. |
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| 13. |
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| 14. |
- Martinez-Fleites, Carlos, et al.
(författare)
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Crystal structures of Clostridium thermocellum xyloglucanase, XGH74A, reveal the structural basis for xyloglucan recognition and degradation
- 2006
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 281:34, s. 24922-24933
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Tidskriftsartikel (refereegranskat)abstract
- The enzymatic degradation of the plant cell wall is central both to the natural carbon cycle and, increasingly, to environmentally friendly routes to biomass conversion, including the production of biofuels. The plant cell wall is a complex composite of cellulose microfibrils embedded in diverse polysaccharides collectively termed hemicelluloses. Xyloglucan is one such polysaccharide whose hydrolysis is catalyzed by diverse xyloglucanases. Here we present the structure of the Clostridium thermocellum xyloglucanase Xgh74A in both apo and ligand-complexed forms. The structures, in combination with mutagenesis data on the catalytic residues and the kinetics and specificity of xyloglucan hydrolysis reveal a complex subsite specificity accommodating seventeen monosaccharide moieties of the multibranched substrate in an open substrate binding terrain.
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| 15. |
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| 16. |
- Baumann, Martin J., et al.
(författare)
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Structural evidence for the evolution of xyloglucanase activity from xyloglucan endo-transglycosylases : Biological implications for cell wall metabolism
- 2007
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Ingår i: The Plant Cell. - : Oxford University Press (OUP). - 1040-4651 .- 1532-298X. ; 19:6, s. 1947-1963
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Tidskriftsartikel (refereegranskat)abstract
- High-resolution, three-dimensional structures of the archetypal glycoside hydrolase family 16 (GH16) endo-xyloglucanases Tm-NXG1 and Tm-NXG2 from nasturtium (Tropaeolum majus) have been solved by x-ray crystallography. Key structural features that modulate the relative rates of substrate hydrolysis to transglycosylation in the GH16 xyloglucan-active enzymes were identified by structure-function studies of the recombinantly expressed enzymes in comparison with data for the strict xyloglucan endo-transglycosylase Ptt-XET16-34 from hybrid aspen ( Populus tremula 3 Populus tremuloides). Production of the loop deletion variant Tm-NXG1-Delta YNIIG yielded an enzyme that was structurally similar to Ptt- XET16-34 and had a greatly increased transglycosylation: hydrolysis ratio. Comprehensive bioinformatic analyses of XTH gene products, together with detailed kinetic data, strongly suggest that xyloglucanase activity has evolved as a gain of function in an ancestral GH16 XET to meet specific biological requirements during seed germination, fruit ripening, and rapid wall expansion.
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| 17. |
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| 18. |
- Cortina-Gil, D., et al.
(författare)
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One-neutron knockout of O-23
- 2005
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-601X .- 1434-6001. ; 25, s. 343-346
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Konferensbidrag (refereegranskat)abstract
- Breakup reactions were used to study the ground-state configuration of the neutron-rich isotope O-23. The O-22 fragments produced in one-nucleon removal from O-23 at 938 MeV/nucleon in a carbon target were detected in coincidence with de-exciting gamma rays, allowing to discern between 220 ground-state and excited-states contributions. From the comparison of exclusive experimental momentum distributions for the one-neutron removal channel to theoretical momentum distributions calculated in an Eikonal model for the knockout process, and spin and parity assignment of I-pi = 1/2(+) was deduced for the 230 ground state. This result solved the existent experimental discrepancy.
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| 19. |
- Kohl, S, et al.
(författare)
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CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia
- 2005
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 13:3, s. 302-308
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Tidskriftsartikel (refereegranskat)abstract
- Achromatopsia is a congenital, autosomal recessively inherited disorder characterized by a lack of color discrimination, low visual acuity (<0.2), photophobia, and nystagmus. Mutations in the genes for CNGA3, CNGB3, and GNAT2 have been associated with this disorder. Here, we analyzed the spectrum and prevalence of CNGB3 gene mutations in a cohort of 341 independent patients with achromatopsia. In 163 patients, CNGB3 mutations could be identified. A total of 105 achromats carried apparent homozygous mutations, 44 were compound (double) heterozygotes, and 14 patients had only a single mutant allele. The derived CNGB3 mutation spectrum comprises 28 different mutations including 12 nonsense mutations, eight insertions and/or deletions, five putative splice site mutations, and three missense mutations. Thus, the majority of mutations in the CNGB3 gene result in significantly altered and/or truncated polypeptides. Several mutations were found recurrently, in particular a 1 bp deletion, c.1148delC, which accounts for over 70% of all CNGB3 mutant alleles. In conclusion, mutations in the CNGB3 gene are responsible for approximately 50% of all patients with achromatopsia. This indicates that the CNGB3/ACHM3 locus on chromosome 8q21 is the major locus for achromatopsia in patients of European origin or descent.
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| 20. |
- Mark, Pekka, et al.
(författare)
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Analysis of nasturtium TmNXG1 complexes by crystallography and molecular dynamics provides detailed insight into substrate recognition by family GH16 xyloglucan endo-transglycosylases and endo-hydrolases
- 2009
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Ingår i: Proteins. - : Wiley. - 0887-3585 .- 1097-0134. ; 75:4, s. 820-836
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Tidskriftsartikel (refereegranskat)abstract
- Reorganization and degradation of the wall crosslinking and seed storage polysaccharide xyloglucan by glycoside hydrolase family 16 (GH16) endo-transglycosylases and hydrolases are crucial to the growth of the majority of land plants, affecting processes as diverse as germination, morphogenesis, and fruit ripening. A high-resolution, three-dimensional structure of a nasturtium (Tropaeolum majus) endo-xyloglucanase loop mutant, TmNXG1-Delta YNIIG, with an ohgosaccharide product bound in the negative active-site subsites, has been solved by X-ray crystallography. Comparison of this novel complex to that of the strict xyloglucan endotransglycosylase PttXET16-34 from hybrid aspen (Populus tremula x tremuloides), previously solved with a xylogluco-oligosaccharide bound in the positive subsites, highlighted key protein structures that affect the disparate catalytic activities displayed by these closely related enzymes. Combination of these "partial" active-site complexes through molecular dynamics simulations in water allowed modeling of wild-type TmNXG1, TmNXG1-Delta YNIIG, and wild-type PttXET16-34 in complex with a xyloglucan octadecasaccharide spanning the entire catalytic cleft. A comprehensive analysis of these full-length complexes underscored the importance of various loops lining the active site. Subtle differences leading to a tighter hydrogen bonding pattern on the negative (glycosyl donor) binding subsites, together with loop flexibility on the positive (glycosyl acceptor) binding subsites appear to favor hydrolysis over transglycosylation in GH16 xyloglucan-active enzymes.
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| 21. |
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| 22. |
- Ebbers-Baumann, A, et al.
(författare)
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Embedding point sets into plane graphs of small dilation
- 2005
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Ingår i: Algorithms and Computation / Lecture notes in computer science. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 1611-3349 .- 0302-9743. - 3540309357 ; 3827, s. 5-16
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Konferensbidrag (refereegranskat)abstract
- Let S be a set of points in the plane. What is the minimum possible dilation of all plane graphs that contain S? Even for a set S as simple as five points evenly placed on the circle, this question seems hard to answer; it is not even clear if there exists a lower bound >1. In this paper we provide the first upper and lower bounds for the embedding problem. 1. Each finite point set can be embedded into the vertex set of a finite triangulation of dilation <= 1.1247. 2. Each embedding of a closed convex curve has dilation >= 1.00157. 3. Let P be the plane graph that results from intersecting n infinite families of equidistant, parallel lines in general position. Then the vertex set of P has dilation >= 2/root 3 approximate to 1.1547.
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| 23. |
- Ibatullin, Farid M., et al.
(författare)
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A Real-Time Fluorogenic Assay for the Visualization of Glycoside Hydrolase Activity in Planta
- 2009
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Ingår i: Plant Physiology. - : Oxford University Press (OUP). - 0032-0889 .- 1532-2548. ; 151:4, s. 1741-1750
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Tidskriftsartikel (refereegranskat)abstract
- There currently exists a diverse array of molecular probes for the in situ localization of polysaccharides, nucleic acids, and proteins in plant cells, including reporter enzyme strategies (e. g. protein-glucuronidase fusions). In contrast, however, there is a paucity of methods for the direct analysis of endogenous glycoside hydrolases and transglycosidases responsible for cell wall remodeling. To exemplify the potential of fluorogenic resorufin glycosides to address this issue, a resorufin beta-glycoside of a xylogluco-oligosaccharide (XXXG-beta-Res) was synthesized as a specific substrate for in planta analysis of XEH activity. The resorufin aglycone is particularly distinguished for high sensitivity in muro assays due to a low pK(a) (5.8) and large extinction coefficient (epsilon 62,000 M-1 cm(-1)), long-wavelength fluorescence (excitation 571 nm/emission 585 nm), and high quantum yield (0.74) of the corresponding anion. In vitro analyses demonstrated that XXXG-beta-Res is hydrolyzed by the archetypal plant XEH, nasturtium (Tropaeolum majus) NXG1, with classical Michaelis-Menten substrate saturation kinetics and a linear dependence on both enzyme concentration and incubation time. Further, XEH activity could be visualized in real time by observing the localized increase in fluorescence in germinating nasturtium seeds and Arabidopsis (Arabidopsis thaliana) inflorescent stems by confocal microscopy. Importantly, this new in situ XEH assay provides an essential complement to the in situ xyloglucan endotransglycosylase assay, thus allowing delineation of the disparate activities encoded by xyloglucan endotransglycosylase/hydrolase genes directly in plant tissues. The observation that XXXG-beta-Res is also hydrolyzed by diverse microbial XEHs indicates that this substrate, and resorufin glycosides in general, may find broad applicability for the analysis of wall restructuring by polysaccharide hydrolases during morphogenesis and plant-microbe interactions.
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| 24. |
- Ibatullin, Farid M., et al.
(författare)
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Kinetic analyses of retaining endo-(xylo)glucanases from plant and microbial sources using new chromogenic xylogluco-oligosaccharide aryl glycosides
- 2008
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 47:29, s. 7762-7769
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Tidskriftsartikel (refereegranskat)abstract
- A library of phenyl beta-glycosides of xylogluco-oligosaccharides was synthesized via a chemoenzymatic approach to produce new, specific substrates for xyloglucanases. Tamarind xyloglucan was completely hydrolyzed to four, variably galactosylated component oligosaccharides based on GlC(4) backbones, using a Trichoderma endo-glucanase mixture. Oligosaccharide complexity could be further reduced by beta-galactosidase treament. Subsequent per-O-acetylation, alpha-bromination, phase-transfer glycosylation, and Zemplen deprotection yielded phenyl glycosides of XXXG and XLLG oligosaccharides with a broad range of aglycon pK(a) values. Kinetic and product analysis of the action of the archetypal plant endo-xyloglucanase, Tropaeolum majus NXG1, on these compounds indicated that formation of the glycosyl-enzyme intermediate was rate-limiting in the case of phenol leaving groups with pK(a) values of >7, leading exclusively to substrate hydrolysis. Conversely, substrates with aglycon pK(a) values of 5.4 gave rise to a significant amount of transglycosylation products, indicating a change in the relative rates of formation and breakdown of the glycosyl-enzyme, intermediate for these faster substrates. Notably, comparison of the initial rates of XXXG-Ar and XLLG-Ar conversion indicated that catalysis by TmNXG1 was essentially insensitive to the presence of galactose in the negative subsites for all leaving groups. More broadly, analysis of a selection of enzymes from CAZy families GH 5, 12, and 16 indicated that the phenyl glycosides are substrates for anomeric configuration-retaining endo-xyloglucanases but are not substrates for strict xyloglucan endo-transglycosylases (XETs). The relative activities of the GH 5, 12, and 16 endo-xyloglucanases toward GGGG-CNP, XXXG-CNP, and XLLG-CNP reflected those observed using analogous high molar mass polysaccharides. These new chromogenic substrates may thus find wide application in the discovery, screening, and detailed kinetic analysis of new xyloglucan-active enzymes.
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| 25. |
- Jin, Shaobo, et al.
(författare)
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Notch signaling regulates platelet-derived growth factor receptor-beta expression in vascular smooth muscle cells
- 2008
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Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 102:12, s. 1483-1491
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Tidskriftsartikel (refereegranskat)abstract
- Notch signaling is critically important for proper architecture of the vascular system, and mutations in NOTCH3 are associated with CADASIL, a stroke and dementia syndrome with vascular smooth muscle cell (VSMC) dysfunction. In this report, we link Notch signaling to platelet-derived growth factor (PDGF) signaling, a key determinant of VSMC biology, and show that PDGF receptor (PDGFR)-beta is a novel immediate Notch target gene. PDGFR-beta expression was upregulated by Notch ligand induction or by activated forms of the Notch receptor. Moreover, upregulation of PDGFR-beta expression in response to Notch activation critically required the Notch signal integrator CSL. In primary VSMCs, PDGFR-beta expression was robustly upregulated by Notch signaling, leading to an augmented intracellular response to PDGF stimulation. In newborn Notch3-deficient mice, PDGFR-beta expression was strongly reduced in the VSMCs that later develop an aberrant morphology. In keeping with this, PDGFR-beta upregulation in response to Notch activation was reduced also in Notch3-deficient embryonic stem cells. Finally, in VSMCs from a CADASIL patient carrying a NOTCH3 missense mutation, upregulation of PDGFR-beta mRNA and protein in response to ligand-induced Notch activation was significantly reduced. In sum, these data reveal a hierarchy for 2 important signaling systems, Notch and PDGF, in the vasculature and provide insights into how dysregulated Notch signaling perturbs VSMC differentiation and function.
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