Look Beyond Plasma Membrane Biophysics: Revealing Considerable Variability of the Dipole Potential Between Plasma and Organelle Membranes of Living Cells.

Due to the lack of measurement techniques suitable for examining compartments of intact, living cells, membrane biophysics is almost exclusively investigated in the plasma membrane despite the fact that its alterations in intracellular organelles may also contribute to disease pathogenesis. Here, we employ a novel, easy-to-use, confocal microscopy-based approach utilizing F66, an environment-sensitive fluorophore in combination with fluorescent organelle markers and quantitative image analysis to determine the magnitude of the molecular order-related dipole potential in the plasma membrane and intracellular organelles of various tumor and neural cell lines. Our comparative analysis demonstrates considerable intracellular variations of the dipole potential that may be large enough to modulate protein functions, with an inward decreasing gradient on the route of the secretory/endocytic pathway (plasma membrane >> lysosome > Golgi > endoplasmic reticulum), whereas mitochondrial membranes are characterized by a dipole potential slightly larger than that of lysosomes.

Lack of Clinically Meaningful Effect of Cariprazine on the Pharmacokinetics of a Combined Oral Contraceptive.

Introduction: Cariprazine (CAR) is a potent dopamine receptor partial agonist antipsychotic approved by the EMA and the FDA. To address the uncertainty regarding the effectiveness of hormonal contraceptives during CAR co-administration and whether a second barrier method is necessary, a drug-drug interaction study with an oral contraceptive was conducted post-approval.

Methods: The phase I, fixed-sequence multicenter study involved two periods with 24 patients with schizophrenia, aiming to evaluate the effect of CAR on the pharmacokinetics (PK) of a combined oral contraceptive (COC) containing 30 μg ethinylestradiol (EE) and 150 μg levonorgestrel (LNG).

Coadministration of Cariprazine with a Moderate CYP3A4 Inhibitor in Patients with Schizophrenia: Implications for Dose Adjustment and Safety Monitoring.

Background: Cariprazine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6.

Aim: This study aimed to evaluate the effects of erythromycin, a moderate cytochrome P450 (CYP)3A4 inhibitor, on the pharmacokinetics of cariprazine in male patients with schizophrenia, and to assess the influence of CYP2D6 phenotypes on cariprazine metabolism.

Methods: Forty-two patients received oral doses of 1.

Novel insights into the modulation of the voltage-gated potassium channel K1.3 activation gating by membrane ceramides.

Membrane lipids extensively modulate the activation gating of voltage-gated potassium channels (K), however, much less is known about the mechanisms of ceramide and glucosylceramide actions including which structural element is the main intramolecular target and whether there is any contribution of indirect, membrane biophysics-related mechanisms to their actions. We used two-electrode voltage-clamp fluorometry capable of recording currents and fluorescence signals to simultaneously monitor movements of the pore domain (PD) and the voltage sensor domain (VSD) of the K1.3 ion channel after attaching an MTS-TAMRA fluorophore to a cysteine introduced into the extracellular S3-S4 loop of the VSD.

The Application of Goal Attainment Scaling in Cervical Dystonia - An Exploratory Observational Pilot Study.

Background: Due to its heterogeneous manifestation an individualized approach to reach therapeutic goals in cervical dystonia (CD) is advantageous.

Objectives: The aim of the current study was to adapt goal attainment scaling (GAS) to drive the management of CD.

Methods: 38 patients with CD, regularly treated with botulinum neurotoxin (BoNT), were involved in the current exploratory observational pilot study.

Clinical features of cervical dystonia patients classified by the COL-CAP concept and treated with ultrasound-guided botulinum neurotoxin.

Background And Purpose: Cervical dystonia (CD) is the most common form of focal dystonias, where the identification of the involved muscles, the determination of optimal botulinum neurotoxin A (BoNT-A) dose per muscle injection, and precise targeting may be challenging. The aim of the current study is to compare local centre data with international data, enabling the identification of population and methodological factors behind the differences, thereby further improvement of the care of Hungarian patients with CD.

Methods: The data of all consecutive CD patients, who were injected with BoNT-A at the botulinum neurotoxin outpatient clinic at the Department of Neurology, University of Szeged between 11 August and 21 September 2021, were retrospectively collected and analysed in a cross-sectional manner.

An ω-3, but Not an ω-6 Polyunsaturated Fatty Acid Decreases Membrane Dipole Potential and Stimulates Endo-Lysosomal Escape of Penetratin.

Although the largely positive intramembrane dipole potential (DP) may substantially influence the function of transmembrane proteins, its investigation is deeply hampered by the lack of measurement techniques suitable for high-throughput examination of living cells. Here, we describe a novel emission ratiometric flow cytometry method based on F66, a 3-hydroxiflavon derivative, and demonstrate that 6-ketocholestanol, cholesterol and 7-dehydrocholesterol, saturated stearic acid (SA) and ω-6 γ-linolenic acid (GLA) increase, while ω-3 α-linolenic acid (ALA) decreases the DP. These changes do not correlate with alterations in cell viability or membrane fluidity.

Formation of amorphous calcium carbonate in caves and its implications for speleothem research.

Speleothem deposits are among the most valuable continental formations in paleoclimate research, as they can be dated using absolute dating methods, and they also provide valuable climate proxies. However, alteration processes such as post-depositional mineralogical transformations can significantly influence the paleoclimatic application of their geochemical data. An innovative sampling and measurement protocol combined with scanning and transmission electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy is presented, demonstrating that carbonate precipitating from drip water in caves at ~10 °C contains amorphous calcium carbonate (ACC) that later transforms to nanocrystalline calcite.