Molecular determinants of hippocampal oscillatory activity

In vitro electrophysiological studies in genetically modified mice with a deletion of the GluR-A subunit in parvalbumin-positive GABAergic interneurons (PV-GluR-A KO mice) provided evidence for the involvement of this cell-population in the generation of hippocampal network synchrony. Besides, these mice displayed several alterations in hippocampus-dependent cognitive tasks (Fuchs et al., 2007). To study the characteristics of hippocampal network synchrony thoroughly, we applied in vivo electrophysiological measurements in freely moving animals. We used tetrode and silicon probe hippocampal recordings from mutant and wildtype (WT) animals and compared cellular activity obtained from pyramidal cells and interneurons as well as network activity. The results can be summarized as follows: 1. PV-GluR-A KO mice exhibited increased ripple-power compared to WT mice. The underlying mechanism cannot be accounted for by an augmented cellular activity during ripples but by an increased phase-modulation of both pyramidal cells and interneurons as indicated by the unitary analysis. 2. The decreased gamma-power in the PV-GluR-A KO mice revealed by in vitro measurements could not be corroborated by the in vivo study. However, a reduction in gamma-frequency could be identified during REM-sleep of the PV-GluR-A KO mice. The phase-preference of pyramidal cells during gamma-oscillations was not different between genotypes. However, there was a delay of the phase-preference of interneurons in PV-GluR-A KO compared with WT mice. 3. The firing rate of pyramidal cells during theta-oscillations was decreased in PV-GluR-A KO mice whereas that of interneurons did not change significantly. We propose that the pyramidal cells’ underperformance is due to the altered function of interneurons. 4. Pyramidal cells were more “bursty” in PV-GluR-A mutants. The increased “burstiness” occurred during theta-, gamma- and ripple-oscillations. We think that the suboptimal work of interneurons makes pyramidal cell firing less “predictable” and maybe temporary fluctuations in the excitatory and inhibitory network state can disturb the optimal modes of pyramidal cell-discharge. In summary, this in vivo study provides direct evidence that PV-positive GABAergic interneurons play a crucial role in the generation of synchronous network activity in the hippocampus

Új módszertani lehetőségek és ezek alkalmazása a hormonális rendszer daganatainak genetikai kivizsgálásában

The technical developments leading to revolution in clinical genetic testing offer new approaches for patients with cancer. From one mutation or one gene approach the scale of genetic testing moved to whole exome or whole genome scale. It is well known that many tumours are genetically determined ans they are part of familial tumour syndromes. In addition, some mutations indicate specific molecular targeted therapies. Although sampling and sample preparation are different for testing germline and somatic mutations, the technical background of the analysis is the same. The aim of clinical genetic testing is to identify patients who are carriers of disease-causing mutations or to test tumour tissue for the presence of genetic alterations which may be targets for therapeutic approaches. In this review the authors summarize novel possibilities offered by next-generation sequencing in clinical genetic testing of patients with endocrine tumours. In addition, the authors review recent guidelines on technical and ethical issues related to these novel methods. Orv. Hetil., 2015, 156(51), 2063-2069

Dynamic configuration of the CMS Data Acquisition cluster

The CMS Data Acquisition cluster, which runs around 10000 applications, is configured dynamically at run time. XML configuration documents determine what applications are executed on each node and over what networks these applications communicate. Through this mechanism the DAQ System may be adapted to the required performance, partitioned in order to perform (test-) runs in parallel, or re-structured in case of hardware faults. This paper presents the CMS DAQ Configurator tool, which is used to generate comprehensive configurations of the CMS DAQ system based on a high-level description given by the user. Using a database of configuration templates and a database containing a detailed model of hardware modules, data and control links, nodes and the network topology, the tool automatically determines which applications are needed, on which nodes they should run, and over which networks the event traffic will flow. The tool computes application parameters and generates the XML configuration documents as well as the configuration of the run-control system. The performance of the tool and operational experience during CMS commissioning and the first LHC runs are discussed

The Run Control and Monitoring System of the CMS Experiment

The CMS experiment at the LHC at CERN will start taking data in 2008. To configure, control and monitor the experiment during data-taking the Run Control and Monitoring System (RCMS) was developed. This paper describes the architecture and the technology used to implement the RCMS, as well as the deployment and commissioning strategy of this important component of the online software for the CMS experiment

High Level Trigger Configuration and Handling of Trigger Tables in the CMS Filter Farm

The CMS experiment at the CERN Large Hadron Collider is currently being commissioned and is scheduled to collect the first pp collision data in 2008. CMS features a two-level trigger system. The Level-1 trigger, based on custom hardware, is designed to reduce the collision rate of 40 MHz to approximately 100 kHz. Data for events accepted by the Level-1 trigger are read out and assembled by an Event Builder. The High Level Trigger (HLT) employs a set of sophisticated software algorithms, to analyze the complete event information, and further reduce the accepted event rate for permanent storage and analysis. This paper describes the design and implementation of the HLT Configuration Management system. First experiences with commissioning of the HLT system are also reported

An analysis of the control hierarchy modeling of the CMS detector control system

The supervisory level of the Detector Control System (DCS) of the CMS experiment is implemented using Finite State Machines (FSM), which model the behaviours and control the operations of all the sub-detectors and support services. The FSM tree of the whole CMS experiment consists of more than 30.000 nodes. An analysis of a system of such size is a complex task but is a crucial step towards the improvement of the overall performance of the FSM system. This paper presents the analysis of the CMS FSM system using the micro Common Representation Language 2 (mcrl2) methodology. Individual mCRL2 models are obtained for the FSM systems of the CMS sub-detectors using the ASF+SDF automated translation tool. Different mCRL2 operations are applied to the mCRL2 models. A mCRL2 simulation tool is used to closer examine the system. Visualization of a system based on the exploration of its state space is enabled with a mCRL2 tool. Requirements such as command and state propagation are expressed using modal mu-calculus and checked using a model checking algorithm. For checking local requirements such as endless loop freedom, the Bounded Model Checking technique is applied. This paper discusses these analysis techniques and presents the results of their application on the CMS FSM system

The absence of P2X7 receptors (P2rx7) on non-haematopoietic cells leads to selective alteration in mood-related behaviour with dysregulated gene expression and stress reactivity in mice

The purpose of this study was to explore how genetic deletion and pharmacological antagonism of the P2X7 receptor (P2rx7) alter mood-related behaviour, gene expression and stress reactivity in the brain. The forced swim test (FST), tail suspension test (TST) and amphetamine-induced hyperlocomotion (AH) tests were used in wild-type (P2rx7+/+) and P2rx7-deficient (P2rx7-/-) mice. Biogenic amine levels were analysed in the amygdala and striatum, adrenocorticotropic hormone (ACTH) and corticosterone levels were measured in the plasma and pituitary after restraint stress. Chimeric mice were generated by bone marrow transplantation. A whole genome microarray analysis with real-time polymerase chain reaction validation was performed on the amygdala. In the absence of P2rx7s decreased behavioural despair in the FST, reduced immobility in the TST and attenuated amphetamine-induced hyperactivity were detected. Basal norepinephrine levels were elevated in the amygdala, whereas stress-induced ACTH and corticosterone responses were alleviated in P2rx7-/- mice. Sub-acute treatment with the selective P2rx7 antagonist, Brilliant Blue G, reproduced the effect of genetic deletion in the TST and AH test in P2rx7+/+ but not P2rx7-/- mice. No change in behavioural phenotype was observed in chimeras lacking the P2rx7 in their haematopoietic compartment. Whole genome microarray analysis indicated a widespread up- and down-regulation of genes crucial for synaptic function and neuroplasticity by genetic deletion. Here, we present evidence that the absence of P2rx7s on non-haematopoietic cells leads to a mood-stabilizing phenotype in several behavioural models and suggest a therapeutic potential of P2rx7 antagonists for the treatment of mood disorders

Common Genetic Variants of the Human Steroid 21-Hydroxylase Gene (CYP21A2) Are Related to Differences in Circulating Hormone Levels

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Hungarian Scientific Research Fund (OTKA, PD100648 (AP)) Technology Innovation Fund, National Developmental Agency (KTIA-AIK-2012-12-1-0010). AP is the recipient of a “Lendület” grant from the Hungarian Academy of Sciences

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio