Reduced protein expression of the phosphodiesterases PDE4A4 and PDE4A8 in AIP mutation positive somatotroph adenomas

© 2018 Type 4 phosphodiesterases (PDE4s) of the large PDE enzyme superfamily have unique specificity for cAMP and may, therefore, be relevant for somatotroph tumorigenesis. Somatotroph adenomas typically overexpress PDEs probably as part of a compensatory mechanism to reduce cAMP levels. The rat PDE4A5 isoform (human homolog PDE4A4) interacts with the AIP protein, coded by a tumour suppressor gene mutated in a subgroup of familial isolated pituitary adenomas (FIPAs). PDE4A8 is the closest related isoform of PDE4A4. We aimed to evaluate the expression of both PDE4A4 and PDE4A8 in GH cells of AIP-mutated adenomas and compare their expression with that in GH cells from sporadic AIP-mutation negative GH-secreting adenomas, where we had shown previously that both PDE4A4 and PDE4A8 isoforms had been over-expressed. Confocal immunofluorescence analysis showed that both PDE4A8 and PDE4A4 had lower expression in AIP-mutated somatotropinoma samples compared to sporadic GH-secreting tumours (P < 0.0001 for both). Based on the association of low PDE4A4 and PDE4A8 expression with germline AIP-mutations positive samples we suggest that lack of AIP hinders the upregulation of PDE4A8 and PDE4A4 protein seen in sporadic somatotrophinomas. These data point to a unique disturbance of the cAMP-PDE pathway in AIP-mutation positive adenomas, which may help to explain their well-described poor response to somatostatin analogues.Grant sponsor: NIH RO1-GM58553 to GBB, The Bolger Prostate Cancer Research Fund to GBB, and the National Cancer Institute of the National Institutes of Health to the University of Alabama at Birmingham Comprehensive Cancer Center under award number P30 CA013148 (for generation of monoclonal antibodies

Aqueductal developmental venous anomaly as an unusual cause of congenital hydrocephalus: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Aqueductal stenosis may be caused by a number of etiologies including congenital stenosis, tumor, inflammation, and, very rarely, vascular malformation. However, aqueductal stenosis caused by a developmental venous anomaly presenting as congenital hydrocephalus is even more rare, and, to the best of our knowledge, has not yet been reported in the literature. In this study, we review the literature and report the first case of congenital hydrocephalus associated with aqueductal stenosis from a developmental venous anomaly.</p> <p>Case presentation</p> <p>The patient is a three-day-old, African-American baby girl with a prenatal diagnosis of hydrocephalus. She presented with a full fontanelle, splayed sutures, and macrocephaly. Postnatal magnetic resonance imaging showed triventricular hydrocephalus, suggesting aqueductal stenosis. Examination of the T1-weighted sagittal magnetic resonance imaging enhanced with gadolinium revealed a developmental venous anomaly passing through the orifice of the aqueduct. We treated the patient with a ventriculoperitoneal shunt.</p> <p>Conclusions</p> <p>Ten cases of aqueductal stenosis due to venous lesions have been reported and, although these venous angiomas and developmental venous anomalies are usually considered congenital lesions, all 10 cases became symptomatic as older children and adults. Our case is the first in which aqueductal stenosis caused by a developmental venous anomaly presents as congenital hydrocephalus. We hope adding to the literature will improve understanding of this very uncommon cause of hydrocephalus and, therefore, will aid in treatment.</p

Revealing the high-energy electronic excitations underlying the onset of high-temperature superconductivity in cuprates

In strongly-correlated systems the electronic properties at the Fermi energy (EF) are intertwined with those at high energy scales. One of the pivotal challenges in the field of high-temperature superconductivity (HTSC) is to understand whether and how the high energy scale physics associated with Mott-like excitations (|E-EF|&gt;1 eV) is involved in the condensate formation. Here we show the interplay between the many-body high-energy CuO2 excitations at 1.5 and 2 eV and the onset of HTSC. This is revealed by a novel optical pump supercontinuum-probe technique, which provides access to the dynamics of the dielectric function in Y-Bi2212 over an extended energy range, after the photoinduced suppression of the superconducting pairing. These results unveil an unconventional mechanism at the base of HTSC both below and above the optimal hole concentration required to attain the maximum critical temperature (Tc)

Search for Kaluza-Klein Graviton Emission in ppˉp\bar{p} Collisions at s=1.8\sqrt{s}=1.8 TeV using the Missing Energy Signature

We report on a search for direct Kaluza-Klein graviton production in a data sample of 84 ${pb}^{-1}$ of \ppb collisions at $\sqrt{s}$ = 1.8 TeV, recorded by the Collider Detector at Fermilab. We investigate the final state of large missing transverse energy and one or two high energy jets. We compare the data with the predictions from a $3+1+n$-dimensional Kaluza-Klein scenario in which gravity becomes strong at the TeV scale. At 95% confidence level (C.L.) for $n$=2, 4, and 6 we exclude an effective Planck scale below 1.0, 0.77, and 0.71 TeV, respectively.Comment: Submitted to PRL, 7 pages 4 figures/Revision includes 5 figure

Studying the Underlying Event in Drell-Yan and High Transverse Momentum Jet Production at the Tevatron

We study the underlying event in proton-antiproton collisions by examining the behavior of charged particles (transverse momentum pT > 0.5 GeV/c, pseudorapidity |\eta| < 1) produced in association with large transverse momentum jets (~2.2 fb-1) or with Drell-Yan lepton-pairs (~2.7 fb-1) in the Z-boson mass region (70 < M(pair) < 110 GeV/c2) as measured by CDF at 1.96 TeV center-of-mass energy. We use the direction of the lepton-pair (in Drell-Yan production) or the leading jet (in high-pT jet production) in each event to define three regions of \eta-\phi space; toward, away, and transverse, where \phi is the azimuthal scattering angle. For Drell-Yan production (excluding the leptons) both the toward and transverse regions are very sensitive to the underlying event. In high-pT jet production the transverse region is very sensitive to the underlying event and is separated into a MAX and MIN transverse region, which helps separate the hard component (initial and final-state radiation) from the beam-beam remnant and multiple parton interaction components of the scattering. The data are corrected to the particle level to remove detector effects and are then compared with several QCD Monte-Carlo models. The goal of this analysis is to provide data that can be used to test and improve the QCD Monte-Carlo models of the underlying event that are used to simulate hadron-hadron collisions.Comment: Submitted to Phys.Rev.

Measurement of the average time-integrated mixing probability of b-flavored hadrons produced at the Tevatron

We have measured the number of like-sign (LS) and opposite-sign (OS) lepton pairs arising from double semileptonic decays of $b$ and $\bar{b}$-hadrons, pair-produced at the Fermilab Tevatron collider. The data samples were collected with the Collider Detector at Fermilab (CDF) during the 1992-1995 collider run by triggering on the existence of $\mu \mu$ and $e \mu$ candidates in an event. The observed ratio of LS to OS dileptons leads to a measurement of the average time-integrated mixing probability of all produced $b$-flavored hadrons which decay weakly, $\bar{\chi} = 0.152 \pm 0.007$ (stat.) $\pm 0.011$ (syst.), that is significantly larger than the world average $\bar{\chi} = 0.118 \pm 0.005$.Comment: 47 pages, 10 figures, 15 tables Submitted to Phys. Rev.

Precision measurement of the top quark mass from dilepton events at CDF II

We report a measurement of the top quark mass, M_t, in the dilepton decay channel of $t\bar{t}\to b\ell'^{+}\nu_{\ell'}\bar{b}\ell^{-}\bar{\nu}_{\ell}$ using an integrated luminosity of 1.0 fb^{-1} of p\bar{p} collisions collected with the CDF II detector. We apply a method that convolutes a leading-order matrix element with detector resolution functions to form event-by-event likelihoods; we have enhanced the leading-order description to describe the effects of initial-state radiation. The joint likelihood is the product of the likelihoods from 78 candidate events in this sample, which yields a measurement of M_{t} = 164.5 \pm 3.9(\textrm{stat.}) \pm 3.9(\textrm{syst.}) \mathrm{GeV}/c^2, the most precise measurement of M_t in the dilepton channel.Comment: 7 pages, 2 figures, version includes changes made prior to publication by journa

Measurement of the Ratios of Branching Fractions B(Bs -> Ds pi pi pi) / B(Bd -> Dd pi pi pi) and B(Bs -> Ds pi) / B(Bd -> Dd pi)

Using 355 pb^-1 of data collected by the CDF II detector in \ppbar collisions at sqrt{s} = 1.96 TeV at the Fermilab Tevatron, we study the fully reconstructed hadronic decays B -> D pi and B -> D pi pi pi. We present the first measurement of the ratio of branching fractions B(Bs -> Ds pi pi pi) / B(Bd -> Dd pi pi pi) = 1.05 pm 0.10 (stat) pm 0.22 (syst). We also update our measurement of B(Bs -> Ds pi) / B(Bd -> Dd pi) to 1.13 pm 0.08 (stat) pm 0.23 (syst) improving the statistical uncertainty by more than a factor of two. We find B(Bs -> Ds pi) = [3.8 pm 0.3 (stat) pm 1.3 (syst)] \times 10^{-3} and B(Bs -> Ds pi pi pi) = [8.4 pm 0.8 (stat) pm 3.2 (syst)] \times 10^{-3}.Comment: 7 pages, 2 figure

Cross Section Measurements of High-pTp_T Dilepton Final-State Processes Using a Global Fitting Method

We present a new method for studying high-$p_T$ dilepton events ($e^{\pm}e^{\mp}$, $\mu^{\pm}\mu^{\mp}$, $e^{\pm}\mu^{\mp}$) and simultaneously extracting the production cross sections of $p\bar{p} \to t\bar{t}$, $p\bar{p} \to W^+W^-$, and p\bar{p} \to \ztt at a center-of-mass energy of $\sqrt{s} = 1.96$ TeV. We perform a likelihood fit to the dilepton data in a parameter space defined by the missing transverse energy and the number of jets in the event. Our results, which use $360 {\rm pb^{-1}}$ of data recorded with the CDF II detector at the Fermilab Tevatron Collider, are $\sigma(t\bar{t}) = 8.5_{-2.2}^{+2.7}$ pb, $\sigma(W^+W^-) = 16.3^{+5.2}_{-4.4}$ pb, and \sigma(\ztt) =291^{+50}_{-46} pb.Comment: 20 pages, 2 figures, to be submitted to PRD-R

Measurement of the Dipion Mass Spectrum in X(3872) -> J/Psi Pi+ Pi- Decays

We measure the dipion mass spectrum in X(3872)--> J/Psi Pi+ Pi- decays using 360 pb-1 of pbar-p collisions at 1.96 TeV collected with the CDF II detector. The spectrum is fit with predictions for odd C-parity (3S1, 1P1, and 3DJ) charmonia decaying to J/Psi Pi+ Pi-, as well as even C-parity states in which the pions are from Rho0 decay. The latter case also encompasses exotic interpretations, such as a D0-D*0Bar molecule. Only the 3S1 and J/Psi Rho hypotheses are compatible with our data. Since 3S1 is untenable on other grounds, decay via J/Psi Rho is favored, which implies C=+1 for the X(3872). Models for different J/Psi-Rho angular momenta L are considered. Flexibility in the models, especially the introduction of Rho-Omega interference, enable good descriptions of our data for both L=0 and 1.Comment: 7 pages, 4 figures -- Submitted to Phys. Rev. Let