K channel targeting impairs DNA repair and invasiveness of patient-derived glioblastoma stem cells in culture and orthotopic mouse xenografts which only in part is predictable by K expression levels.

Prognosis of glioblastoma patients is still poor despite multimodal therapy. The highly brain-infiltrating growth in concert with a pronounced therapy resistance particularly of mesenchymal glioblastoma stem-like cells (GSCs) has been proposed to contribute to therapy failure. Recently, we have shown that a mesenchymal-to-proneural mRNA signature of patient derived GSC-enriched (pGSC) cultures associates with in vitro radioresistance and gel invasion.

Discovery of a Small Molecule Activator of Slack (Kcnt1) Potassium Channels That Significantly Reduces Scratching in Mouse Models of Histamine-Independent and Chronic Itch.

Various disorders are accompanied by histamine-independent itching, which is often resistant to the currently available therapies. Here, it is reported that the pharmacological activation of Slack (Kcnt1, K1.1), a potassium channel highly expressed in itch-sensitive sensory neurons, has therapeutic potential for the treatment of itching.

Climate change and public health in Germany - A synthesis of options for action from the German status report on climate change and health 2023.

Background: This article represents the conclusion of the updated German status report on climate change and health, which was jointly written by authors from over 30 national institutions and organisations. The objectives are (a) to synthesise the options for action formulated in the report, (b) to combine them into clusters and guiding principles, (c) to address the success factors for implementation, and (d) to combine the options for action into target parameters.

Methods: The options for action from the individual contributions of the status report were systematically recorded and categorised (n=236).

Efficacy of combined tumor irradiation and K3.1-targeting with TRAM-34 in a syngeneic glioma mouse model.

The intermediate-conductance calcium-activated potassium channel K3.1 has been proposed to be a new potential target for glioblastoma treatment. This study analyzed the effect of combined irradiation and K3.

BK channels sustain neuronal Ca oscillations to support hippocampal long-term potentiation and memory formation.

Mutations of large conductance Ca- and voltage-activated K channels (BK) are associated with cognitive impairment. Here we report that CA1 pyramidal neuron-specific conditional BK knock-out (cKO) mice display normal locomotor and anxiety behavior. They do, however, exhibit impaired memory acquisition and retrieval in the Morris Water Maze (MWM) when compared to littermate controls (CTRL).

Slack K channels limit kainic acid-induced seizure severity in mice by modulating neuronal excitability and firing.

Mutations of the Na-activated K channel Slack (KCNT1) are associated with terrible epilepsy syndromes that already begin in infancy. Here we report increased severity of acute kainic acid-induced seizures in adult and juvenile Slack knockout mice (Slack) in vivo. Fittingly, we find exacerbation of cell death following kainic acid exposure in organotypic hippocampal slices as well as dissociated hippocampal cultures from Slack in vitro.

Indium α radiation from a MetalJet X-ray source: the long way to a successful charge-density investigation.

The MetalJet X-ray source provides indium α radiation with a wavelength even shorter than Ag radiation. This paper reports on problematic spectral impurities and presents possible countermeasures so that collection of data with excellent quality up to a high resolution is possible. It is demonstrated that these data can be used in the refinement of a multipole model, the results of which are used for a topological analysis to assess the bonding situation in a sulfur ylide compound.

Indium α radiation from a MetalJet X-ray source: comparison of the Eiger2 CdTe and Photon III detectors.

The MetalJet source makes available new α radiation wavelengths for use in X-ray diffraction experiments. The purpose of this paper is to demonstrate the application of indium α radiation in independent-atom model refinement, as well as approaches using aspherical atomic form factors. The results vary greatly depending on the detector employed, as the energy cut-off of the Eiger2 CdTe provides a solution to a unique energy contamination problem of the MetalJet In radiation, which the Photon III detector cannot provide.

A donor-supported silavinylidene and silylium ylides: boroles as a flexible platform for versatile Si(ii) chemistry.

Electron-deficient, -aromatic 2,5-disilyl boroles are shown to be a flexibly adaptive molecular platform with regards to SiMe mobility in their reaction with the nucleophilic donor-stabilised precursor dichloro silylene SiCl(IDipp). Depending on the substitution pattern, selective formation of two fundamentally different products of rivalling formation pathways is achieved. Formal addition of the dichlorosilylene gives the 5,5-dichloro-5-sila-6-borabicyclo[2.

One silicon atom of bis(silylene) functions as a selective Lewis base under adduct formation with a Lewis acid.

Herein, we describe the facile and selective one-pot synthetic route to silylene-aluminum and silylene-gallium adducts. Reduction of silylene LSiCl (L = PhC(NBu)) with KC in the presence of bulky and sterically hindered cyclopentadienyl aluminum Cp'''AlCl (Cp''' = 1,2,4-BuCH) and gallium [η-Cp'''Ga(μ-Cl)Cl] to afford the Lewis acid-base adducts η-Cp'''M(Cl) ← Si(L)-SiL (M = Al, 1; M = Ga, 3). To confirm the formation of the Lewis acid-base adduct, the bis(silylene) LSi(I)-Si(I)L reacts with Cp'''AlI to form η-Cp'''Al(I) ← Si(L)-SiL (2).

Implementation of an interactive mobile application to pilot a rapid assay to detect HIV drug resistance mutations in Kenya.

Usability is an overlooked aspect of implementing lab-based assays, particularly novel assays in low-resource-settings. Esoteric instructions can lead to irreproducible test results and patient harm. To address these issues, we developed a software application based on "Aquarium", a laboratory-operating system run on a computer tablet that provides step-by-step digital interactive instructions, protocol management, and sample tracking.

Linear and Bent Cp* Si: Reversible Phase Transition of a Key Molecule.

The solid-state structure of decamethylsilicocene Cp* Si with a bent and a linear molecule in the same unit cell was so far considered an exception in relation to the structures of its all-bent heavier analogues Cp* E with E=Ge, Sn, Pb. Here, we present the solution to this conundrum by reporting a low-temperature phase, where all three symmetrically independent molecules are present in a bent formation. This reversible enantiotropic phase transition occurs in the temperature range between 80 K and 130 K and provides a rationale for the unexpected linear molecule based in entropy beyond hand-waving explanations such as electronic reasons or packing effects.

Tumoricidal, Temozolomide- and Radiation-Sensitizing Effects of K3.1 K Channel Targeting In Vitro Are Dependent on Glioma Cell Line and Stem Cell Fraction.

Reportedly, the intermediate-conductance Ca-activated potassium channel K3.1 contributes to the invasion of glioma cells into healthy brain tissue and resistance to temozolomide and ionizing radiation. Therefore, K3.

Insertion Reaction of MeSiN with Bis(germylene).

Herein, we describe the redox reaction of bis(germylene) PhC(NBu)Ge-Ge(NBu)CPh with different equivalents of MeSiN affording two distinct products. The reaction of MeSiN with bis-germylene in a 1:1 molar ratio results in compound at -78 °C; however, treatment of bis-germylene with a 2.1 equiv of MeSiN at room temperature results in compound .

IK channels control breast cancer metabolism including AMPK-driven autophagy.

Ca-activated K channels of intermediate conductance (IK) are frequently overexpressed in breast cancer (BC) cells, while IK channel depletion reduces BC cell proliferation and tumorigenesis. This raises the question, of whether and mechanistically how IK activity interferes with the metabolic activity and energy consumption rates, which are fundamental for rapidly growing cells. Using BC cells obtained from MMTV-PyMT tumor-bearing mice, we show that both, glycolysis and mitochondrial ATP-production are reduced in cells derived from IK-deficient breast tumors.

Slack Potassium Channels Modulate TRPA1-Mediated Nociception in Sensory Neurons.

The transient receptor potential (TRP) ankyrin type 1 (TRPA1) channel is highly expressed in a subset of sensory neurons where it acts as an essential detector of painful stimuli. However, the mechanisms that control the activity of sensory neurons upon TRPA1 activation remain poorly understood. Here, using in situ hybridization and immunostaining, we found TRPA1 to be extensively co-localized with the potassium channel Slack (K1.

Cysteine-Rich LIM-Only Protein 4 (CRP4) Promotes Atherogenesis in the ApoE Mouse Model.

Vascular smooth muscle cells (VSMCs) can switch from their contractile state to a synthetic phenotype resulting in high migratory and proliferative capacity and driving atherosclerotic lesion formation. The cysteine-rich LIM-only protein 4 (CRP4) reportedly modulates VSM-like transcriptional signatures, which are perturbed in VSMCs undergoing phenotypic switching. Thus, we hypothesized that CRP4 contributes to adverse VSMC behaviours and thereby to atherogenesis in vivo.

Trapping X-ray Radiation Damage from Homolytic Se-C Bond Cleavage in BnSeSeBn Crystals (Bn=benzyl, CH C H ).

Irradiation of dibenzyl diselenide BnSeSeBn with X-ray or UV-light cleaves the Se-C and the Se-Se bonds, inducing stable and metastable radical states. They are inevitably important to all natural and life sciences. Structural changes due to X-ray-induced Se-C bond-cleavage could be pin-pointed in various high-resolution X-ray diffraction experiments for the first time.

Hirshfeld atom refinement based on projector augmented wave densities with periodic boundary conditions.

Hirshfeld atom refinement (HAR) is an X-ray diffraction refinement method that, in numerous publications, has been shown to give H-atom bond lengths in close agreement with neutron diffraction derived values. Presented here is a first evaluation of an approach using densities derived from projector augmented wave (PAW) densities with three-dimensional periodic boundary conditions for HAR. The results show an improvement over refinements that neglect the crystal environment or treat it classically, while being on a par with non-periodic approximations for treating the solid-state environment quantum mechanically.

Slick Potassium Channels Control Pain and Itch in Distinct Populations of Sensory and Spinal Neurons in Mice.

Background: Slick, a sodium-activated potassium channel, has been recently identified in somatosensory pathways, but its functional role is poorly understood. The authors of this study hypothesized that Slick is involved in processing sensations of pain and itch.

Methods: Immunostaining, in situ hybridization, Western blot, and real-time quantitative reverse transcription polymerase chain reaction were used to investigate the expression of Slick in dorsal root ganglia and the spinal cord.

Loss of central mineralocorticoid or glucocorticoid receptors impacts auditory nerve processing in the cochlea.

The key auditory signature that may associate peripheral hearing with central auditory cognitive defects remains elusive. Suggesting the involvement of stress receptors, we here deleted the mineralocorticoid and glucocorticoid receptors ( and ) using a CaMKIIα-based tamoxifen-inducible Cre/ approach to generate mice with single or double deletion of central but not cochlear MR and GR. Hearing thresholds of MRGR conditional knockouts () were unchanged, whereas auditory nerve fiber () responses were larger and faster and auditory steady state responses were improved.