812 research outputs found
MAPK phosphorylation of connexin 43 promotes binding of cyclin E and smooth muscle cell proliferation
<p>Rationale: Dedifferentiation of vascular smooth muscle cells (VSMC) leading to a proliferative cell phenotype significantly contributes to the development of atherosclerosis. Mitogen-activated protein kinase (MAPK) phosphorylation of proteins including connexin 43 (Cx43) has been associated with VSMC proliferation in atherosclerosis.</p>
<p>Objective: To investigate whether MAPK phosphorylation of Cx43 is directly involved in VSMC proliferation.</p>
<p>Methods and Results: We show in vivo that MAPK-phosphorylated Cx43 forms complexes with the cell cycle control proteins cyclin E and cyclin-dependent kinase 2 (CDK2) in carotids of apolipoprotein-E receptor null (ApoE−/−) mice and in C57Bl/6 mice treated with platelet-derived growth factor–BB (PDGF). We tested the involvement of Cx43 MAPK phosphorylation in vitro using constructs for full-length Cx43 (Cx43) or the Cx43 C-terminus (Cx43CT) and produced null phosphorylation Ser>Ala (Cx43MK4A/Cx43CTMK4A) and phospho-mimetic Ser>Asp (Cx43MK4D/Cx43CTMK4D) mutations. Coimmunoprecipitation studies in primary VSMC isolated from Cx43 wild-type (Cx43+/+) and Cx43 null (Cx43−/−) mice and analytic size exclusion studies of purified proteins identify that interactions between cyclin E and Cx43 requires Cx43 MAPK phosphorylation. We further demonstrate that Cx43 MAPK phosphorylation is required for PDGF-mediated VSMC proliferation. Finally, using a novel knock-in mouse containing Cx43-MK4A mutation, we show in vivo that interactions between Cx43 and cyclin E are lost and VSMC proliferation does not occur after treatment of carotids with PDGF and that neointima formation is significantly reduced in carotids after injury.</p>
<p>Conclusions: We identify MAPK-phosphorylated Cx43 as a novel interacting partner of cyclin E in VSMC and show that this interaction is critical for VSMC proliferation. This novel interaction may be important in the development of atherosclerotic lesions.</p>
Selective disruption of Tcf7l2 in the pancreatic β cell impairs secretory function and lowers β cell mass.
Type 2 diabetes (T2D) is characterized by β cell dysfunction and loss. Single nucleotide polymorphisms in the T-cell factor 7-like 2 (TCF7L2) gene, associated with T2D by genome-wide association studies, lead to impaired β cell function. While deletion of the homologous murine Tcf7l2 gene throughout the developing pancreas leads to impaired glucose tolerance, deletion in the β cell in adult mice reportedly has more modest effects. To inactivate Tcf7l2 highly selectively in β cells from the earliest expression of the Ins1 gene (∼E11.5) we have therefore used a Cre recombinase introduced at the Ins1 locus. Tcfl2(fl/fl)::Ins1Cre mice display impaired oral and intraperitoneal glucose tolerance by 8 and 16 weeks, respectively, and defective responses to the GLP-1 analogue liraglutide at 8 weeks. Tcfl2(fl/fl)::Ins1Cre islets displayed defective glucose- and GLP-1-stimulated insulin secretion and the expression of both the Ins2 (∼20%) and Glp1r (∼40%) genes were significantly reduced. Glucose- and GLP-1-induced intracellular free Ca(2+) increases, and connectivity between individual β cells, were both lowered by Tcf7l2 deletion in islets from mice maintained on a high (60%) fat diet. Finally, analysis by optical projection tomography revealed ∼30% decrease in β cell mass in pancreata from Tcfl2(fl/fl)::Ins1Cre mice. These data demonstrate that Tcf7l2 plays a cell autonomous role in the control of β cell function and mass, serving as an important regulator of gene expression and islet cell coordination. The possible relevance of these findings for the action of TCF7L2 polymorphisms associated with Type 2 diabetes in man is discussed
Crystallization of a classical two-dimensional electron system: Positional and orientational orders
Crystallization of a classical two-dimensional one-component plasma
(electrons interacting with the Coulomb repulsion in a uniform neutralizing
positive background) is investigated with a molecular dynamics simulation. The
positional and the orientational correlation functions are calculated for the
first time. We have found an indication that the solid phase has a
quasi-long-range (power-law) positional order along with a long-range
orientational order. This indicates that, although the long-range Coulomb
interaction is outside the scope of Mermin's theorem, the absence of ordinary
crystalline order at finite temperatures applies to the electron system as
well. The `hexatic' phase, which is predicted between the liquid and the solid
phases by the Kosterlitz-Thouless-Halperin-Nelson-Young theory, is also
discussed.Comment: 3 pages, 4 figures; Corrected typos; Double columne
Combined CI+MBPT calculations of energy levels and transition amplitudes in Be, Mg, Ca, and Sr
Configuration interaction (CI) calculations in atoms with two valence
electrons, carried out in the V(N-2) Hartree-Fock potential of the core, are
corrected for core-valence interactions using many-body perturbation theory
(MBPT). Two variants of the mixed CI+MBPT theory are described and applied to
obtain energy levels and transition amplitudes for Be, Mg, Ca, and Sr
Isospin-Violating Meson-Nucleon Vertices as an Alternate Mechanism of Charge-Symmetry Breaking
We compute isospin-violating meson-nucleon coupling constants and their
consequent charge-symmetry-breaking nucleon-nucleon potentials. The couplings
result from evaluating matrix elements of quark currents between nucleon states
in a nonrelativistic constituent quark model; the isospin violations arise from
the difference in the up and down constituent quark masses. We find, in
particular, that isospin violation in the omega-meson--nucleon vertex dominates
the class IV CSB potential obtained from these considerations. We evaluate the
resulting spin-singlet--triplet mixing angles, the quantities germane to the
difference of neutron and proton analyzing powers measured in elastic
scattering, and find them commensurate to those computed
originally using the on-shell value of the - mixing amplitude.
The use of the on-shell - mixing amplitude at has been
called into question; rather, the amplitude is zero in a wide class of models.
Our model possesses no contribution from - mixing at , and
we find that omega-meson exchange suffices to explain the measured
analyzing power difference~at~183 MeV.Comment: 20 pages, revtex, 3 uuencoded PostScript figure
A rotação de cultura reduz a matocompetição e aumenta o teor de clorofila e a produtividade do arroz
Knowledge-based energy functions for computational studies of proteins
This chapter discusses theoretical framework and methods for developing
knowledge-based potential functions essential for protein structure prediction,
protein-protein interaction, and protein sequence design. We discuss in some
details about the Miyazawa-Jernigan contact statistical potential,
distance-dependent statistical potentials, as well as geometric statistical
potentials. We also describe a geometric model for developing both linear and
non-linear potential functions by optimization. Applications of knowledge-based
potential functions in protein-decoy discrimination, in protein-protein
interactions, and in protein design are then described. Several issues of
knowledge-based potential functions are finally discussed.Comment: 57 pages, 6 figures. To be published in a book by Springe
Heavy Quarks and Heavy Quarkonia as Tests of Thermalization
We present here a brief summary of new results on heavy quarks and heavy
quarkonia from the PHENIX experiment as presented at the "Quark Gluon Plasma
Thermalization" Workshop in Vienna, Austria in August 2005, directly following
the International Quark Matter Conference in Hungary.Comment: 8 pages, 5 figures, Quark Gluon Plasma Thermalization Workshop
(Vienna August 2005) Proceeding
Proximity effect at superconducting Sn-Bi2Se3 interface
We have investigated the conductance spectra of Sn-Bi2Se3 interface junctions
down to 250 mK and in different magnetic fields. A number of conductance
anomalies were observed below the superconducting transition temperature of Sn,
including a small gap different from that of Sn, and a zero-bias conductance
peak growing up at lower temperatures. We discussed the possible origins of the
smaller gap and the zero-bias conductance peak. These phenomena support that a
proximity-effect-induced chiral superconducting phase is formed at the
interface between the superconducting Sn and the strong spin-orbit coupling
material Bi2Se3.Comment: 7 pages, 8 figure
Demonstration of the temporal matter-wave Talbot effect for trapped matter waves
We demonstrate the temporal Talbot effect for trapped matter waves using
ultracold atoms in an optical lattice. We investigate the phase evolution of an
array of essentially non-interacting matter waves and observe matter-wave
collapse and revival in the form of a Talbot interference pattern. By using
long expansion times, we image momentum space with sub-recoil resolution,
allowing us to observe fractional Talbot fringes up to 10th order.Comment: 17 pages, 7 figure
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