Increased 5-hydroxymethylation levels in the sub ventricular zone of the Alzheimer's brain

© 2016 The Authors. The subventricular zone (SVZ) is a site of neurogenesis in the aging brain, and epigenetic mechanisms have been implicated in regulating the "normal" distribution of new nerve cells into the existing cellular milieu. In a case-control study of human primary SVZ cultures and fixed tissue from the same individuals, we have found significant increases in DNA hydroxymethylation levels in the SVZ of Alzheimer's disease patients compared with nondiseased control subjects. We show that this increase in hydroxymethylation directly correlates to an increase in cellular proliferation in Alzheimer's disease precursor cells, which implicates the hydroxymethylation tag to a higher degree of cellular proliferation

Epigenetic regulation of adult neural stem cells: implications for Alzheimer's disease.

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tReviewExperimental evidence has demonstrated that several aspects of adult neural stem cells (NSCs), including their quiescence, proliferation, fate specification and differentiation, are regulated by epigenetic mechanisms. These control the expression of specific sets of genes, often including those encoding for small non-coding RNAs, indicating a complex interplay between various epigenetic factors and cellular functions.Previous studies had indicated that in addition to the neuropathology in Alzheimer's disease (AD), plasticity-related changes are observed in brain areas with ongoing neurogenesis, like the hippocampus and subventricular zone. Given the role of stem cells e.g. in hippocampal functions like cognition, and given their potential for brain repair, we here review the epigenetic mechanisms relevant for NSCs and AD etiology. Understanding the molecular mechanisms involved in the epigenetic regulation of adult NSCs will advance our knowledge on the role of adult neurogenesis in degeneration and possibly regeneration in the AD brain.Internationale Stichting Alzheimer Onderzoek (ISAO)Netherlands Organization for Scientific Research (NWO)Maastricht University Medical Centre 

Prenatal stress and subsequent exposure to chronic mild stress influence dendritic spine density and morphology in the rat medial prefrontal cortex

<p>Abstract</p> <p>Background</p> <p>Both prenatal stress (PS) and postnatal chronic mild stress (CMS) are associated with behavioral and mood disturbances in humans and rodents. The aim of this study was to reveal putative PS- and/or CMS-related changes in basal spine morphology and density of pyramidal neurons in the rat medial prefrontal cortex (mPFC).</p> <p>Results</p> <p>We show that rats exposed to PS and/or CMS display changes in the morphology and number of basal spines on pyramidal neurons in the mPFC. CMS had a negative effect on spine densities, particularly on spines of the mushroom type, which are considered to form stronger and more stable synapses than other spine types. PS alone did not affect spine densities, but had a negative effect on the ratio of mushroom spines. In addition, PS seemed to make rats less responsive to some of the negative effects of CMS, which supports the notion that PS represents a predictive adaptive response.</p> <p>Conclusion</p> <p>The observed changes may represent a morphological basis of PS- and CMS-related disturbances, and future studies in the field should not only consider total spine densities, but also separate between different spine types.</p

Systems and technologies for objective evaluation of technical skills in laparoscopic surgery

Minimally invasive surgery is a highly demanding surgical approach regarding technical requirements for the surgeon, who must be trained in order to perform a safe surgical intervention. Traditional surgical education in minimally invasive surgery is commonly based on subjective criteria to quantify and evaluate surgical abilities, which could be potentially unsafe for the patient. Authors, surgeons and associations are increasingly demanding the development of more objective assessment tools that can accredit surgeons as technically competent. This paper describes the state of the art in objective assessment methods of surgical skills. It gives an overview on assessment systems based on structured checklists and rating scales, surgical simulators, and instrument motion analysis. As a future work, an objective and automatic assessment method of surgical skills should be standardized as a means towards proficiency-based curricula for training in laparoscopic surgery and its certification

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter