Local GABA concentration is related to network-level resting functional connectivity

Anatomically plausible networks of functionally inter-connected regions have been reliably demonstrated at rest, although the neurochemical basis of these ‘resting state networks’ is not well understood. In this study, we combined magnetic resonance spectroscopy (MRS) and resting state fMRI and demonstrated an inverse relationship between levels of the inhibitory neurotransmitter GABA within the primary motor cortex (M1) and the strength of functional connectivity across the resting motor network. This relationship was both neurochemically and anatomically specific. We then went on to show that anodal transcranial direct current stimulation (tDCS), an intervention previously shown to decrease GABA levels within M1, increased resting motor network connectivity. We therefore suggest that network-level functional connectivity within the motor system is related to the degree of inhibition in M1, a major node within the motor network, a finding in line with converging evidence from both simulation and empirical studies

A multiorganism pipeline for antiseizure drug discovery:Identification of chlorothymol as a novel γ-aminobutyric acidergic anticonvulsant

OBJECTIVE:Current medicines are ineffective in approximately one-third of people with epilepsy. Therefore, new antiseizure drugs are urgently needed to address this problem of pharmacoresistance. However, traditional rodent seizure and epilepsy models are poorly suited to high-throughput compound screening. Furthermore, testing in a single species increases the chance that therapeutic compounds act on molecular targets that may not be conserved in humans. To address these issues, we developed a pipeline approach using four different organisms. METHODS:We sequentially employed compound library screening in the zebrafish, Danio rerio, chemical genetics in the worm, Caenorhabditis elegans, electrophysiological analysis in mouse and human brain slices, and preclinical validation in mouse seizure models to identify novel antiseizure drugs and their molecular mechanism of action. RESULTS:Initially, a library of 1690 compounds was screened in an acute pentylenetetrazol seizure model using D rerio. From this screen, the compound chlorothymol was identified as an effective anticonvulsant not only in fish, but also in worms. A subsequent genetic screen in C elegans revealed the molecular target of chlorothymol to be LGC-37, a worm γ-aminobutyric acid type A (GABAA ) receptor subunit. This GABAergic effect was confirmed using in vitro brain slice preparations from both mice and humans, as chlorothymol was shown to enhance tonic and phasic inhibition and this action was reversed by the GABAA receptor antagonist, bicuculline. Finally, chlorothymol exhibited in vivo anticonvulsant efficacy in several mouse seizure assays, including the 6-Hz 44-mA model of pharmacoresistant seizures. SIGNIFICANCE:These findings establish a multiorganism approach that can identify compounds with evolutionarily conserved molecular targets and translational potential, and so may be useful in drug discovery for epilepsy and possibly other conditions

Minimally Invasive Methods for Re-optimization of the First Permanent Molar Restorations – Two Years Longitudinal Study

The minimum invasive therapy has the same conservative approach of hard dental tissues as in the case of defective restorations. We know the importance of first permanent molar in maintaining homeostasis of the stomatognathic system. Choosing an optimal management solution for the defective restorations from this level by using minimally invasive methods will contribute ultimately to a therapeutic success. The purpose of this study is to assess the clinical situation of composite resin obturations and amalgam of class I, class II and class IV located at the first permanent molar and to monitor and assess the effectiveness of the minimally invasive therapeutic solutions. Restoration assessment was based on the Ryge clinical assessment / modified USPHS. They were divided into five groups according to the recommended needs of minimally invasive treatments. We can say that composite resin restorations and the amalgam of class I, II and V, located at the first permanent molar, with minimal clinical defects, which benefit from minimally invasive therapeutic measures, have kept favorable clinical parameters in the acceptable clinical limits during the two years of study. Alternative methods guided on the principles of minimally invasive therapy increase longevity of direct amalgam and composite resins restorations

Crystallographically amorphous ferrimagnetic alloys: Comparing a localized atomistic spin model with experiments

Contains fulltext : 91679.pdf (publisher's version ) (Open Access

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

"A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7 TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb(-1) to 4.8 fb(-1). Higgs boson decays into oppositely-charged in muon or tau lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, phi, as a function of the Higgs boson mass and for h\/A\/H production in the MSSM as a function of the parameters m(A) and tan beta in the m(h)(max) scenario for m(A) in the range of 90 GeV to 500 GeV.

A new Time-of-flight detector for the R 3 B setup

© 2022, The Author(s).We present the design, prototype developments and test results of the new time-of-flight detector (ToFD) which is part of the R3B experimental setup at GSI and FAIR, Darmstadt, Germany. The ToFD detector is able to detect heavy-ion residues of all charges at relativistic energies with a relative energy precision σΔE/ ΔE of up to 1% and a time precision of up to 14 ps (sigma). Together with an elaborate particle-tracking system, the full identification of relativistic ions from hydrogen up to uranium in mass and nuclear charge is possible.11Nsciescopu