Knockdown of the schizophrenia susceptibility gene TCF4 alters gene expression and proliferation of progenitor cells from the developing human neocortex

BACKGROUND: Common variants in the TCF4 gene are among the most robustly supported genetic risk factors for schizophrenia. Rare TCF4 deletions and loss-of-function point mutations cause Pitt-Hopkins syndrome, a developmental disorder associated with severe intellectual disability. METHODS: To explore molecular and cellular mechanisms by which TCF4 perturbation could interfere with human cortical development, we experimentally reduced the endogenous expression of TCF4 in a neural progenitor cell line derived from the developing human cerebral cortex using RNA interference. Effects on genome-wide gene expression were assessed by microarray, followed by Gene Ontology and pathway analysis of differentially expressed genes. We tested for genetic association between the set of differentially expressed genes and schizophrenia using genome-wide association study data from the Psychiatric Genomics Consortium and competitive gene set analysis (MAGMA). Effects on cell proliferation were assessed using high content imaging. RESULTS: Genes that were differentially expressed following TCF4 knockdown were highly enriched for involvement in the cell cycle. There was a nonsignificant trend for genetic association between the differentially expressed gene set and schizophrenia. Consistent with the gene expression data, TCF4 knockdown was associated with reduced proliferation of cortical progenitor cells in vitro. LIMITATIONS: A detailed mechanistic explanation of how TCF4 knockdown alters human neural progenitor cell proliferation is not provided by this study. CONCLUSION: Our data indicate effects of TCF4 perturbation on human cortical progenitor cell proliferation, a process that could contribute to cognitive deficits in individuals with Pitt-Hopkins Syndrome and risk for schizophrenia

Exploring Triadic Family Relationship Profiles and Their Implications for Adolescents’ Early Substance Initiation

This study examined combinations of warmth and hostility in mother-father-adolescent triadic relationships when adolescents were in 6th grade and associations with adolescent middle school substance initiation. We conducted a latent profile analysis with a sample of 687 two-parent families (52.4% of adolescents were female, mean age = 11.27 at 6th grade). These analyses revealed five profiles of triadic relationships, labeled as: cohesive families (46%, high warmth and low hostility in all three dyads), compensatory families (24%, low interparental warmth but high parent-adolescent warmth), disengaged families (13%, average to low warmth and hostility in three dyads), distressed families (9%, high hostility and low warmth in all three dyads), and conflictual families (8%, high hostility and average warmth in all three dyads). There were significant differences across triadic relationship profiles in rate of alcohol initiation during middle school. Specifically, adolescents in distressed families and conflictual families initiated alcohol at higher rates than adolescents in other types of families. Cohesive families and compensatory families initiated alcohol at the lowest rates among all five types of families. Similar patterns appeared for drunkenness and cigarettes. Implications for family-based interventions to decrease adolescent substance use and future research directions are discussed

Magneto-Acoustic Wave Oscillations in Solar Spicules

Some observations suggest that solar spicules show small amplitude and high frequency oscillations of magneto-acoustic waves, which arise from photospheric granular forcing. We apply the method of MHD seismology to determine the period of kink waves. For this purposes, the oscillations of a magnetic cylinder embedded in a field-free environment is investigated. Finally, diagnostic diagrams displaying the oscillatory period in terms of some equilibrium parameters are provided to allow a comparison between theoretical results and those coming from observations.Comment: 10 pages, 4 fig

Observation of a Coherence Length Effect in Exclusive Rho^0 Electroproduction

Exclusive incoherent electroproduction of the rho^0(770) meson from 1H, 2H, 3He, and 14N targets has been studied by the HERMES experiment at squared four-momentum transfer Q**2>0.4 GeV**2 and positron energy loss nu from 9 to 20 GeV. The ratio of the 14N to 1H cross sections per nucleon, known as the nuclear transparency, was found to decrease with increasing coherence length of quark-antiquark fluctuations of the virtual photon. The data provide clear evidence of the interaction of the quark- antiquark fluctuations with the nuclear medium.Comment: RevTeX, 5 pages, 3 figure

Determination of the Deep Inelastic Contribution to the Generalised Gerasimov-Drell-Hearn Integral for the Proton and Neutron

The virtual photon absorption cross section differences [sigma_1/2-sigma_3/2] for the proton and neutron have been determined from measurements of polarised cross section asymmetries in deep inelastic scattering of 27.5 GeV longitudinally polarised positrons from polarised 1H and 3He internal gas targets. The data were collected in the region above the nucleon resonances in the kinematic range nu < 23.5 GeV and 0.8 GeV**2 < Q**2 < 12 GeV**2. For the proton the contribution to the generalised Gerasimov-Drell-Hearn integral was found to be substantial and must be included for an accurate determination of the full integral. Furthermore the data are consistent with a QCD next-to-leading order fit based on previous deep inelastic scattering data. Therefore higher twist effects do not appear significant.Comment: 6 pages, 3 figures, 1 table, revte

Flavor Decomposition of the Polarized Quark Distributions in the Nucleon from Inclusive and Semi-inclusive Deep-inelastic Scattering

Spin asymmetries of semi-inclusive cross sections for the production of positively and negatively charged hadrons have been measured in deep-inelastic scattering of polarized positrons on polarized hydrogen and 3He targets, in the kinematic range 0.023<x<0.6 and 1 GeV^2<Q^2<10 GeV^2. Polarized quark distributions are extracted as a function of x for up $(u+u_bar) and down (d+d_bar) flavors. The up quark polarization is positive and the down quark polarization is negative in the measured range. The polarization of the sea is compatible with zero. The first moments of the polarized quark distributions are presented. The isospin non-singlet combination Delta_q_3 is consistent with the prediction based on the Bjorken sum rule. The moments of the polarized quark distributions are compared to predictions based on SU(3)_f flavor symmetry and to a prediction from lattice QCD.Comment: 14 pages, 6 figures (eps format), 10 tables in Latex New version contains tables of asymmetries and correlation matri

Erratum to: "Nuclear Effects on R=\sigma_L/\sigma_T in Deep-Inelastic Scattering" Phys.Lett. B475(2000)386

This erratum revokes the main conclusion of a Letter that reported measurements of cross sections for deep-inelastic scattering (DIS) of leptons on $^3$He and $^{14}$N targets, expressed as ratios of $\sigma_A / \sigma_D$ to the cross section on the deuterium target.Comment: 3 pages, 1 figur

The HERMES Spectrometer

The HERMES experiment is collecting data on inclusive and semi-inclusive deep inelastic scattering of polarised positrons from polarised targets of Il, D, and He-3. These data give information on the spin structure of the nucleon. This paper describes the forward angle spectrometer built for this purpose. The spectrometer includes numerous tracking chambers (micro-strip gas chambers, drift and proportional chambers) in front of and behind a 1.3 T.m magnetic field, as well as an extensive set of detectors for particle identification (a lead-glass calorimeter, a pre-shower detector, a transition radiation detector, and a threshold Cherenkov detector). Two of the main features of the spectrometer are its good acceptance and identification of both positrons and hadrons, in particular pions. These characteristics, together with the purity of the targets, are allowing HERMES to make unique contributions to the understanding of how the spins of the quarks contribute to the spin of the nucleon. (C) 1998 Elsevier Science B.V. All rights reserved

H(2p) excitation by 54.4 eV electrons

In response to the recent measurements of the 54.4 eV e-H(2p) reduced Stokes parameters by Gradziel and O'Neill (2004 J. Phys. B: At. Mol. Opt. Phys. 37 1893) we perform corresponding calculations using two recently developed techniques. These are the propagating exterior complex scaling direct approach to the solution of the underlying Schrödinger equation, and the box-based convergent close-coupling method. We find the results to be almost identical to the Laguerre-based convergent close-coupling method of Bray and Stelbovics (1992 Phys. Rev. A 49 1066). Hence we are unable to explain the substantial discrepancy with experiment for the P∼ 3 parameter in the vicinity of 30°