14 research outputs found
Disease- and age-related changes in histone acetylation at gene promoters in psychiatric disorders
Increasing evidence suggests that epigenetic factors have critical roles in gene
regulation in neuropsychiatric disorders and in aging, both of which are
typically associated with a wide range of gene expression abnormalities. Here,
we have used chromatin immunoprecipitation-qPCR to measure levels of acetylated
histone H3 at lysines 9/14 (ac-H3K9K14), two epigenetic marks associated
with transcriptionally active chromatin, at the promoter regions of eight
schizophrenia-related genes in n=82 postmortem prefrontal
cortical samples from normal subjects and those with schizophrenia and bipolar
disorder. We find that promoter-associated ac-H3K9K14 levels are correlated with
gene expression levels, as measured by real-time qPCR for several genes,
including, glutamic acid decarboxylase 1 (GAD1), 5-hydroxytryptamine
receptor 2C (HTR2C), translocase of outer mitochondrial membrane 70
homolog A (TOMM70A) and protein phosphatase 1E (PPM1E).
Ac-H3K9K14 levels of several of the genes tested were significantly negatively
associated with age in normal subjects and those with bipolar disorder, but not
in subjects with schizophrenia, whereby low levels of histone acetylation were
observed in early age and throughout aging. Consistent with this observation,
significant hypoacetylation of H3K9K14 was detected in young subjects with
schizophrenia when compared with age-matched controls. Our results demonstrate
that gene expression changes associated with psychiatric disease and aging
result from epigenetic mechanisms involving histone acetylation. We further find
that treatment with a histone deacetylase (HDAC) inhibitor alters the expression
of several candidate genes for schizophrenia in mouse brain. These findings may
have therapeutic implications for the clinical use of HDAC inhibitors in
psychiatric disorders
A Small Molecule Activator of p300/CBP Histone Acetyltransferase Promotes Survival and Neurite Growth in a Cellular Model of Parkinson’s Disease
First proton-proton collisions at the LHC as observed with the ALICE detector: Measurement of the charged-particle pseudorapidity density at √s = 900 GeV
On 23rd November 2009, during the early commissioning of the CERN Large Hadron Collider (LHC), two counter-rotating proton bunches were circulated for the first time concurrently in the machine, at the LHC injection energy of 450 GeV per beam. Although the proton intensity was very low, with only one pilot bunch per beam, and no systematic attempt was made to optimize the collision optics, all LHC experiments reported a number of collision candidates. In the ALICE experiment, the collision region was centred very well in both the longitudinal and transverse directions and 284 events were recorded in coincidence with the two passing proton bunches. The events were immediately reconstructed and analyzed both online and offline. We have used these events to measure the pseudorapidity density of charged primary particles in the central region. In the range |η|<0.5, we obtain dNch/dη=3. 10±0. 13(stat.)±0. 22(syst.) for all inelastic interactions, and dNch/dη=3.51±0. 15(stat.)±0. 25(syst.) for non-single diffractive interactions. These results are consistent with previous measurements in proton-antiproton interactions at the same centre-of-mass energy at the CERN SppS̄ collider. They also illustrate the excellent functioning and rapid progress of the LHC accelerator, and of both the hardware and software of the ALICE experiment, in this early start-up phase
Multiplicity dependence of pion, kaon, proton and lambda production in p–Pb collisions at √sNN = 5.02 TeV
Inthis Letter, comprehensive results on π±,K±,K0S, p(pbar) and Λ(Λbar) production at mid-rapidity (0< yCMS < 0.5) in p–Pb collisions at √sNN = 5.02 TeV, measured by the ALICE detector at the LHC, are reported. The transverse momentum distributions exhibit a hardening as a function of event multiplicity, which is stronger for heavier particles. This behavior is similar to what has been observed in pp and Pb–Pb collisions at the LHC. The measured pT distributions are compared to d–Au, Au–Au and Pb–Pb results at lower energy and with predictions based on QCD-inspired and hydrodynamic models