14-3-3 promotes sarcolemmal expression of cardiac Ca1.2 and nucleates isoproterenol-triggered channel superclustering.

The L-type Ca channel (Ca1.2) is essential for cardiac excitation-contraction coupling. To contribute to the inward Ca flux that drives Ca-induced-Ca-release, Ca1.

Tonabersat enhances temozolomide-mediated cytotoxicity in glioblastoma by disrupting intercellular connectivity through connexin 43 inhibition.

Glioblastoma cells rely on connexin 43 (Cx43)-based gap junctions (GJs) for intercellular communication, enabling them to integrate into a widely branched malignant network. Although there are promising prospects for new targeted therapies, the lack of clinically feasible GJ inhibitors has impeded their adoption in clinical practice. In the present study, we investigated tonabersat (TO), a blood-brain-barrier-penetrating drug with GJ-inhibitory properties, in regard to its potential to disassemble intercellular connectivity in glioblastoma networks.

Individual differences in functional connectivity during suppression of imagined threat.

Functional magnetic resonance imaging studies typically rely on between-person analyses. To examine individual differences in functional connectivity, we used Group Iterative Multiple Model Estimation and its subgrouping function to analyze functional magnetic resonance imaging data of 54 participants who were suppressing imagined future threat. A two-stage random-effects meta-analytic approach was employed to examine individual differences.

[Prolonged weaning after long-term ventilation due to SARS-CoV-2 infection: a multicenter retrospective analysis].

Unlabelled: Some of the patients with SARS-CoV-2 infection (COVID-19) received invasive ventilation during inpatient care. Weaning from ventilation was difficult for some patients (so-called prolonged weaning).

Patients: Patients (n=751) with prolonged weaning (reason for ventilation "pneumonia" and "acute respiratory failure") from four centers for the period 2011-23 from the "WeanNet" registry were used as a matched group.

Combined inhibition of EZH2 and CDK4/6 perturbs endoplasmic reticulum-mitochondrial homeostasis and increases antitumor activity against glioblastoma.

He, we show that combined use of the EZH2 inhibitor GSK126 and the CDK4/6 inhibitor abemaciclib synergistically enhances antitumoral effects in preclinical GBM models. Dual blockade led to HIF1α upregulation and CalR translocation, accompanied by massive impairment of mitochondrial function. Basal oxygen consumption rate, ATP synthesis, and maximal mitochondrial respiration decreased, confirming disrupted endoplasmic reticulum-mitochondrial homeostasis.