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&gt

Tumori maligni delle ghiandole salivari della laringe: un'unica review istituzionale

I tumori a istotipo salivare della laringe sono molto rari, con pochi report in letteratura in merito al loro andamento clinico. Nel presente manoscritto discutiamo un'esperienza di 10 anni presso una singola struttura. Abbiamo condotto una review retrospettiva della casistica di un centro di oncologia della testa e del collo di terzo livello. I pazienti sono stati individuati mediante analisi di un database e sono stati revisionati da un Anatomo Patologo testa collo. I dati inerenti la clinica, le modalità di trattamento e gli esiti sono stati prelevati da archivi elettronici. Sono stati inclusi sei pazienti nello studio, con un range di età dai 44 ai 69 anni. Tutti e sei erano affetti da neoplasie maligne a istotipo salivare della laringe. Gli istotipi includevano: tre carcinomi adenoido-cistici (2 sopraglottico, 1 sottoglottico), un carcinoma mucoepidermoidale (sopraglottico), un carcinoma epiteliale-mioepiteliale (sopraglottico), e un adenocarcinoma (transglottico). Tutti sono stati sottoposti a trattamento chirurgico (2 chirurgie laser, 4 open) e 5 dei 6 pazienti sono stati successivamente sottoposti a terapia adjuvante (4 a radioterapia, 1 a radio-chemioterapia concomitante). Un paziente era fumatore; nessun paziente aveva storia di abuso di alcolici. A un follow-up con mediana di 4,5 anni nessuno dei pazienti ha presentato recidiva o metastasi locali o a distanza. I tumori a istotipo salivare della laringe si presentano solitamente in pazienti della seconda/terza età, e possono essere trattati con successo mediante approcci multimodali, con un ottimo controllo locoregionale di malattia

Valence-quark distributions in the pion

We calculate the pion's valence-quark momentum-fraction probability distribution using a Dyson-Schwinger equation model. Valence-quarks with an active mass of 0.30 GeV carry 71% of the pion's momentum at a resolving scale q_0=0.54 GeV = 1/(0.37 fm). The shape of the calculated distribution is characteristic of a strongly bound system and, evolved from q_0 to q=2 GeV, it yields first, second and third moments in agreement with lattice and phenomenological estimates, and valence-quarks carrying 49% of the pion's momentum. However, pointwise there is a discrepancy between our calculated distribution and that hitherto inferred from parametrisations of extant pion-nucleon Drell-Yan data.Comment: 8 pages, 3 figures, REVTEX, aps.sty, epsfig.sty, minor corrections, version to appear in PR

Modelling harmonic generation measurements in solids

Harmonic generation measurements typically make use of the plane wave result when extracting values for the nonlinearity parameter, beta, from experimental measurements. This approach, however, ignores the effects of diffraction, attenuation, and receiver integration which are common features in a typical experiment. Our aim is to determine the importance of these effects when making measurements of beta over different sample dimensions, or using different input frequencies. We describe a three-dimensional numerical model designed to accurately predict the results of a typical experiment, based on a quasi-linear assumption. An experiment is designed to measure the axial variation of the fundamental and second harmonic amplitude components in an ultrasonic beam, and the results are compared with those predicted by the model. The absolute b values are then extracted from the experimental data using both the simulation and the standard plane wave result. A difference is observed between the values returned by the two methods, which varies with axial range and input frequency. (C) 2013 Elsevier B. V. All rights reserved.</p

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

Positive-strand RNA viruses—a Keystone Symposia report

Positive-strand RNA viruses have been the cause of several recent outbreaks and epidemics, including the Zika virus epidemic in 2015, the SARS outbreak in 2003, and the ongoing SARS-CoV-2 pandemic. On June 18–22, 2022, researchers focusing on positive-strand RNA viruses met for the Keystone Symposium “Positive-Strand RNA Viruses” to share the latest research in molecular and cell biology, virology, immunology, vaccinology, and antiviral drug development. This report presents concise summaries of the scientific discussions at the symposium

Measurement of the CP-Violating Asymmetry Amplitude sin2β\beta

We present results on time-dependent CP-violating asymmetries in neutral B decays to several CP eigenstates. The measurements use a data sample of about 88 million Y(4S) --> B Bbar decays collected between 1999 and 2002 with the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. We study events in which one neutral B meson is fully reconstructed in a final state containing a charmonium meson and the other B meson is determined to be either a B0 or B0bar from its decay products. The amplitude of the CP-violating asymmetry, which in the Standard Model is proportional to sin2beta, is derived from the decay-time distributions in such events. We measure sin2beta = 0.741 +/- 0.067 (stat) +/- 0.033 (syst) and |lambda| = 0.948 +/- 0.051 (stat) +/- 0.017 (syst). The magnitude of lambda is consistent with unity, in agreement with the Standard Model expectation of no direct CP violation in these modes

A search for the decay B+→K+ννˉB^+ \to K^+ \nu \bar{\nu}

We search for the rare flavor-changing neutral-current decay $B^+ \to K^+ \nu \bar{\nu}$ in a data sample of 82 fb$^{-1}$ collected with the {\sl BABAR} detector at the PEP-II B-factory. Signal events are selected by examining the properties of the system recoiling against either a reconstructed hadronic or semileptonic charged-B decay. Using these two independent samples we obtain a combined limit of ${\mathcal B}(B^+ \to K^+ \nu \bar{\nu})<5.2 \times 10^{-5}$ at the 90% confidence level. In addition, by selecting for pions rather than kaons, we obtain a limit of ${\mathcal B}(B^+ \to \pi^+ \nu \bar{\nu})<1.0 \times 10^{-4}$ using only the hadronic B reconstruction method.Comment: 7 pages, 8 postscript figures, submitted to Phys. Rev. Let

High-reflectivity broadband distributed Bragg reflector lattice matched to ZnTe

We report on the realization of a high quality distributed Bragg reflector with both high and low refractive index layers lattice matched to ZnTe. Our structure is grown by molecular beam epitaxy and is based on binary compounds only. The high refractive index layer is made of ZnTe, while the low index material is made of a short period triple superlattice containing MgSe, MgTe, and ZnTe. The high refractive index step of Delta_n=0.5 in the structure results in a broad stopband and the reflectivity coefficient exceeding 99% for only 15 Bragg pairs.Comment: 4 pages, 3 figure

EuFe2_2As2_2 under high pressure: an antiferromagnetic bulk superconductor

We report the ac magnetic susceptibility $\chi_{ac}$ and resistivity $\rho$ measurements of EuFe$_2$As$_2$ under high pressure $P$. By observing nearly 100% superconducting shielding and zero resistivity at $P$ = 28 kbar, we establish that $P$-induced superconductivity occurs at $T_c \sim$~30 K in EuFe$_2$As$_2$. $\rho$ shows an anomalous nearly linear temperature dependence from room temperature down to $T_c$ at the same $P$. $\chi_{ac}$ indicates that an antiferromagnetic order of Eu$^{2+}$ moments with $T_N \sim$~20 K persists in the superconducting phase. The temperature dependence of the upper critical field is also determined.Comment: To appear in J. Phys. Soc. Jpn., Vol. 78 No.