111 research outputs found
The induction of behavioural sensitization is associated with cocaine-induced structural plasticity in the core (but not shell) of the nucleus accumbens
Repeated exposure to cocaine increases the density of dendritic spines on medium spiny neurons in the nucleus accumbens (Acb) and pyramidal cells in the medial prefrontal cortex (mPFC). To determine if this is associated with the development of psychomotor sensitization, rats were given daily i.p. injections of 15 mg/kg of cocaine (or saline) for 8 days, either in their home cage (which failed to induce significant psychomotor sensitization) or in a distinct and relatively novel test cage (which induced robust psychomotor sensitization). Their brains were obtained 2 weeks after the last injection and processed for Golgi–Cox staining. In the Acb core (AcbC) cocaine treatment increased spine density only in the group that developed psychomotor sensitization (i.e. in the Novel but not Home group), and there was a significant positive correlation between the degree of psychomotor sensitization and spine density. In the Acb shell (AcbS) cocaine increased spine density to the same extent in both groups; i.e. independent of psychomotor sensitization. In the mPFC cocaine increased spine density in both groups, but to a significantly greater extent in the Novel group. Furthermore, when rats were treated at Home with a higher dose of cocaine (30 mg/kg), cocaine now induced psychomotor sensitization in this context, and also increased spine density in the AcbC. Thus, the context in which cocaine is experienced influences its ability to reorganize patterns of synaptic connectivity in the Acb and mPFC, and the induction of psychomotor sensitization is associated with structural plasticity in the AcbC and mPFC, but not the AcbS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73532/1/j.1460-9568.2004.03612.x.pd
The effect of age on DNA methylation in whole blood among Bangladeshi men and women
Background: It is well-known that methylation changes occur as humans age, however, understanding how age-related changes in DNA methylation vary by sex is lacking. In this study, we characterize the effect of age on DNA methylation in a sex-specific manner and determine if these effects vary by genomic context. We used the Illumina HumanMethylation 450 K array and DNA derived from whole blood for 400 adult participants (189 males and 211 females) from Bangladesh to identify age-associated CpG sites and regions and characterize the location of these age-associated sites with respect to CpG islands (vs. shore, shelf, or open sea) and gene regions (vs. intergenic). We conducted a genome-wide search for age-associated CpG sites (among 423,604 sites) using a reference-free approach to adjust for cell type composition (the R package RefFreeEWAS) and performed an independent replication analysis of age-associated CpGs. Results: The number of age-associated CpGs (p < 5 x 10-8) were 986 among men and 3479 among women of which 2027(63.8%) and 572 (64.1%) replicated (using Bonferroni adjusted p < 1.2 × 10-5). For both sexes, age-associated CpG sites were more likely to be hyper-methylated with increasing age (compared to hypo-methylated) and were enriched in CpG islands and promoter regions compared with other locations and all CpGs on the array. Although we observed strong correlation between chronological age and previously-developed epigenetic age models (r ≈ 0.8), among our top (based on lowest p-value) age-associated CpG sites only 12 for males and 44 for females are included in these prediction models, and the median chronological age compared to predicted age was 44 vs. 51.7 in males and 45 vs. 52.1 in females. Conclusions: Our results describe genome-wide features of age-related changes in DNA methylation. The observed associations between age and methylation were generally consistent for both sexes, although the associations tended to be stronger among women. Our population may have unique age-related methylation changes that are not captured in the established methylation-based age prediction model we used, which was developed to be non-tissue-specific
A Bayesian analysis of pentaquark signals from CLAS data
We examine the results of two measurements by the CLAS collaboration, one of
which claimed evidence for a pentaquark, whilst the other found no
such evidence. The unique feature of these two experiments was that they were
performed with the same experimental setup. Using a Bayesian analysis we find
that the results of the two experiments are in fact compatible with each other,
but that the first measurement did not contain sufficient information to
determine unambiguously the existence of a . Further, we suggest a
means by which the existence of a new candidate particle can be tested in a
rigorous manner.Comment: 5 pages, 3 figure
eta-prime photoproduction on the proton for photon energies from 1.527 to 2.227 GeV
Differential cross sections for the reaction gamma p -> eta-prime p have been
measured with the CLAS spectrometer and a tagged photon beam with energies from
1.527 to 2.227 GeV. The results reported here possess much greater accuracy
than previous measurements. Analyses of these data indicate for the first time
the coupling of the etaprime N channel to both the S_11(1535) and P_11(1710)
resonances, known to couple strongly to the eta N channel in photoproduction on
the proton, and the importance of j=3/2 resonances in the process.Comment: 6 pages, 3 figure
First measurement of direct photoproduction on the proton
We report on the results of the first measurement of exclusive
meson photoproduction on protons for GeV and GeV. Data were collected with the CLAS detector at the Thomas
Jefferson National Accelerator Facility. The resonance was detected via its
decay in the channel by performing a partial wave analysis of the
reaction . Clear evidence of the meson
was found in the interference between and waves at GeV. The -wave differential cross section integrated in the mass range of
the was found to be a factor of 50 smaller than the cross section
for the meson. This is the first time the meson has been
measured in a photoproduction experiment
Vagus Nerve Stimulation Paired With Rehabilitation for Upper Limb Motor Impairment and Function After Chronic Ischemic Stroke: Subgroup Analysis of the Randomized, Blinded, Pivotal, VNS-REHAB Device Trial
Background Vagus Nerve Stimulation (VNS) paired with rehabilitation improved upper extremity impairment and function in a recent pivotal, randomized, triple-blind, sham-controlled trial in people with chronic arm weakness after stroke. Objective We aimed to determine whether treatment effects varied across candidate subgroups, such as younger age or less injury. Methods Participants were randomized to receive rehabilitation paired with active VNS or rehabilitation paired with sham stimulation (Control). The primary outcome was the change in impairment measured by the Fugl-Meyer Assessment Upper Extremity (FMA-UE) score on the first day after completion of 6-weeks in-clinic therapy. We explored the effect of VNS treatment by sex, age (≥62 years), time from stroke (>2 years), severity (baseline FMA-UE score >34), paretic side of body, country of enrollment (USA vs UK) and presence of cortical involvement of the index infarction. We assessed whether there was any interaction with treatment. Findings The primary outcome increased by 5.0 points (SD 4.4) in the VNS group and by 2.4 points (SD 3.8) in the Control group (P=.001, between group difference 2.6, 95% CI 1.03-4.2). The between group difference was similar across all subgroups and there were no significant treatment interactions. There was no important difference in rates of adverse events across subgroups. Conclusion The response was similar across subgroups examined. The findings suggest that the effects of paired VNS observed in the VNS-REHAB trial are likely to be consistent in wide range of stroke survivors with moderate to severe upper extremity impairment
Deeply Virtual Compton Scattering Beam-Spin Asymmetries
The beam spin asymmetries in the hard exclusive electroproduction of photons
on the proton (ep -> epg) were measured over a wide kinematic range and with
high statistical accuracy. These asymmetries result from the interference of
the Bethe-Heitler process and of deeply virtual Compton scattering. Over the
whole kinematic range (x_B from 0.11 to 0.58, Q^2 from 1 to 4.8 GeV^2, -t from
0.09 to 1.8 GeV^2), the azimuthal dependence of the asymmetries is compatible
with expectations from leading-twist dominance, A = a*sin(phi)/[1+c*cos(phi)].
This extensive set of data can thus be used to constrain significantly the
generalized parton distributions of the nucleon in the valence quark sector.Comment: 1 tex file (6 pages), 4 (eps) figure
Beam Spin Asymmetries in DVCS with CLAS at 4 .8 GeV
We report measurements of the beam spin asymmetry in Deeply Virtual Compton
Scattering (DVCS) at an electron beam energy of 4.8 GeV using the CLAS detector
at the Thomas Jefferson National Accelerator Facility. The DVCS beam spin
asymmetry has been measured in a wide range of kinematics, 1(GeV/c)
(GeV/c), , and 0.1 (GeV/c)
(GeV/c), using the reaction \pEpX. The number of
H and H events are separated in
each bin by a fit to the line shape of the H
distribution. The validity of the method was studied in detail using
experimental and simulated data. It was shown, that with the achieved missing
mass squared resolution and the available statistics, the separation of DVCS-BH
and events can reliably be done with less than 5% uncertainty. The
- and -dependences of the moments of the asymmetry are
extracted and compared with theoretical calculations
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
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