GABA-A Channel Subunit Expression in Human Glioma Correlates with Tumor Histology and Clinical Outcome

GABA (γ-aminobutyric acid) is the main inhibitory neurotransmitter in the CNS and is present in high concentrations in presynaptic terminals of neuronal cells. More recently, GABA has been ascribed a more widespread role in the control of cell proliferation during development where low concentrations of extrasynaptic GABA induce a tonic activation of GABA receptors. The GABA-A receptor consists of a ligand-gated chloride channel, formed by five subunits that are selected from 19 different subunit isoforms. The functional and pharmacological properties of the GABA-A channels are dictated by their subunit composition. Here we used qRT-PCR to compare mRNA levels of all 19 GABA-A channel subunits in samples of human glioma (n = 29) and peri-tumoral tissue (n = 5). All subunits except the ρ1 and ρ3 subunit were consistently detected. Lowest mRNA levels were found in glioblastoma compared to gliomas of lower malignancy, except for the θ subunit. The expression and cellular distribution of the α1, γ1, ρ2 and θ subunit proteins was investigated by immunohistochemistry on tissue microarrays containing 87 gliomas grade II. We found a strong co-expression of ρ2 and θ subunits in both astrocytomas (r = 0.86, p<0.0001) and oligodendroglial tumors (r = 0.66, p<0.0001). Kaplan-Meier analysis and Cox proportional hazards modeling to estimate the impact of GABA-A channel subunit expression on survival identified the ρ2 subunit (p = 0.043) but not the θ subunit (p = 0.64) as an independent predictor of improved survival in astrocytomas, together with established prognostic factors. Our data give support for the presence of distinct GABA-A channel subtypes in gliomas and provide the first link between specific composition of the A-channel and patient survival

Regulation of monocyte cell fate by blood vessels mediated by Notch signalling

A population of monocytes, known as Ly6Clo monocytes, patrol blood vessels by crawling along the vascular endothelium. Here we show that endothelial cells control their origin through Notch signalling. Using combinations of conditional genetic deletion strategies and cell-fate tracking experiments we show that Notch2 regulates conversion of Ly6Chi monocytes into Ly6Clo monocytes in vivo and in vitro, thereby regulating monocyte cell fate under steady-state conditions. This process is controlled by Notch ligand delta-like 1 (Dll1) expressed by a population of endothelial cells that constitute distinct vascular niches in the bone marrow and spleen in vivo, while culture on recombinant DLL1 induces monocyte conversion in vitro. Thus, blood vessels regulate monocyte conversion, a form of committed myeloid cell fate regulation

Regulation of monocyte cell fate by blood vessels mediated by Notch signalling

A population of monocytes, known as Ly6C(lo) monocytes, patrol blood vessels by crawling along the vascular endothelium. Here we show that endothelial cells control their origin through Notch signalling. Using combinations of conditional genetic deletion strategies and cell-fate tracking experiments we show that Notch2 regulates conversion of Ly6C(hi) monocytes into Ly6C(lo) monocytes in vivo and in vitro, thereby regulating monocyte cell fate under steady-state conditions. This process is controlled by Notch ligand delta-like 1 (Dll1) expressed by a population of endothelial cells that constitute distinct vascular niches in the bone marrow and spleen in vivo, while culture on recombinant DLL1 induces monocyte conversion in vitro. Thus, blood vessels regulate monocyte conversion, a form of committed myeloid cell fate regulation

Sealing Systems in German Spent Fuel Storage Facilities

This paper describes the current issues related to sealing devices in the German on-site spent fuel dry storage facilities (SFSFs) related to the Germany’s energy transition. Accordingly, there is a need of future investigations for improving techniques in order to achieve better radiation protection and occupational safety during safeguards verification of spent fuel casks stored in SFSFs. In the context of phasing out nuclear energy production, the eight still operating reactors will be successively disconnected from the power grid by the end of 2022 at the latest. The nuclear material of all power reactors has to be removed prior to decommissioning of the reactor building. The defueling of reactors increases the handling operations at these sites especially by the temporary higher number of cask loadings. Accordingly, the number of transfers of these loaded casks (dual purpose: transport and storage casks) from the reactor to the SFSF will further increase as well. By end of 2027, it is foreseen that all spent fuel assemblies will have been loaded into casks. After their transfer to SFSFs, the SFSFs will have a static inventory of more than 1,000 casks, because no receipts or shipments are expected following the final reactor shut down. The spent fuel packed in casks will be stored in interim dry storages for several decades until a repository for heat generating high level waste is available. The casks may be difficult to be accessed; especially the seals attached at the protection plate on top of the approx. 6 meter high casks. A seal verification that involves the replacement of the seal will require more time and will lead to a higher radiation dose for both inspector and storage staff than easier in-situ verification or seal verification by Remote Data Transmission (RDT). Given this situation optimization of safeguards concepts and sealing systems devices applied is needed. Solutions are required to ease the verification of the casks and to minimize the exposure of the inspectors and storage staff

Sealing Systems in German Spent Fuel Storage Facilities

This paper describes the current issues related to sealing devices in the German on-site spent fuel dry storage facilities (SFSFs) related to the Germany’s energy transition. Accordingly, there is a need of future investigations for improving techniques in order to achieve better radiation protection and occupational safety during safeguards verification of spent fuel casks stored in SFSFs. In the context of phasing out nuclear energy production, the eight still operating reactors will be successively disconnected from the power grid by the end of 2022 at the latest. The nuclear material of all power reactors has to be removed prior to decommissioning of the reactor building. The defueling of reactors increases the handling operations at these sites especially by the temporary higher number of cask loadings. Accordingly, the number of transfers of these loaded casks (dual purpose: transport and storage casks) from the reactor to the SFSF will further increase as well. By end of 2027, it is foreseen that all spent fuel assemblies will have been loaded into casks. After their transfer to SFSFs, the SFSFs will have a static inventory of more than 1,000 casks, because no receipts or shipments are expected following the final reactor shut down. The spent fuel packed in casks will be stored in interim dry storages for several decades until a repository for heat generating high level waste is available. The casks may be difficult to be accessed; especially the seals attached at the protection plate on top of the approx. 6 meter high casks. A seal verification that involves the replacement of the seal will require more time and will lead to a higher radiation dose for both inspector and storage staff than easier in-situ verification or seal verification by Remote Data Transmission (RDT). Given this situation optimization of safeguards concepts and sealing systems devices applied is needed. Solutions are required to ease the verification of the casks and to minimize the exposure of the inspectors and storage staff

Directed forgetting, event-related potentials and nicotine

Fifteen male users of oral snuff performed a directed forgetting task after over-night abstinence and after administration of oral snuff. Directed forgetting tasks use cues to classify items for differential reporting at test, emphasising the need for strategic encoding. Recognition was better after nicotine administration, but we found no evidence for greater strategic control, as hypothetically reflected in successful compliance with the directed forgetting instructions. Reaction time decreased after nicotine administration. Performance among fifteen controls was unaffected over two sessions

The methanoreductosome: a high-molecular-weight enzyme complex in the methanogenic bacterium strain Gö1 that contains components of the methylreductase system.

The methanogenic bacterium strain Gö1 harbors a high-molecular-weight enzyme complex containing methyl coenzyme M methylreductase as revealed by immunoelectron microscopy. This complex consists of a spherelike, hollow head piece, in the wall of which a number of copies of the methyl coenzyme M methylreductase are located. It is named Rc (c indicates collector). Intimately bound to it is a group of additional subunits of unknown composition referred to as Rm (m indicates mediator). Electron microscopy of negatively stained samples indicated that Rm contains a functional pore or channel which connects the internal volume of Rc with the outside. The RcRm complex is named Rs (s indicates spherelike). This complex was often found detached from the inside of the cytoplasmic membrane when membrane vesicles were investigated. However, Rs was also seen attached to a third component of the complex located in the membrane, the attachment being mediated by Rm. This membrane part of the complex is designated Rt (t indicates translocator). It consists of subunits with unknown composition. When Rs is attached to the membrane, the pore in Rm appears to be plugged by Rt. This indicates that the internal volume in Rc is in contact, via the pore in Rm, with Rt. The RcRmRt complex is referred to as methanoreductosome. Functional implications of the structural organization of the methylreductase system are discussed in view of methane formation and the creation of a transmembrane proton gradient used by the cell for ATP synthesis