Functional Characterisation of Alternative Oxidase Protein Isoproteins in Arabidopsis thaliana.

The Alternative Oxidase (AOX) is encoded by a small gene family in plants. While being one of the most intensively studied plant mitochondrial proteins, it is primarily only one isoform, AOX1a, that is well studied. We investigated the sub-and neo-functionalisation of AOX isoforms in Arabidopsis thaliana by constructing over-expressing lines for all five AOX isoforms in an aox1a knock-out mutant line, where no AOX protein can be detected.

The Phenomenology of Tics in Adults: Data From the Calgary and Paris Adult Tic Disorders Registry.

Introduction: This study investigated the phenomenology of tics in adults with primary tic disorders (Tourette syndrome, persistent motor or phonic tic disorders) and how these features are influenced by sex. It also examined the prevalence of comorbid psychiatric conditions and psychotropic medication use.

Methods: A cross-sectional study was conducted on 227 adults with primary tic disorders from the Calgary and Paris Adult Tic Registry.

Safety and tolerability of intravenous liposomal GM1 in patients with Parkinson disease: A single-center open-label clinical phase I trial (NEON trial).

Background: Parkinson disease (PD) is a chronic progressive neurodegenerative disorder leading to motor and non-motor impairment, often resulting in severe loss of quality of life. There are symptomatic treatments without effect on the progression of PD. A disease-modifying treatment that could ideally stop the neurodegenerative process is direly needed.

A new process-based approach for defining karst aquifer vulnerability to contamination risks under global changes.

Karst groundwater resources play a crucial role in global water supply. But due to their intrinsic heterogeneity, karst aquifers are especially vulnerable to contamination and environmental changes. To sustain karst water quality, assessing karst aquifer vulnerability to contamination and revealing the influence of changing environmental conditions on karst vulnerability are essential.

Characterizing Antisense Oligonucleotide-Induced Histopathology Findings in Spinal Cord of Mauritius Cynomolgus Monkeys by Molecular Localization Investigation.

The safety of a 2'--methoxyethyl antisense oligonucleotide (ASO) was investigated in Mauritius cynomolgus monkeys in a 41-week Good Laboratory Practice (GLP) toxicity study after multiple intrathecal (IT) administrations. Histopathological examination revealed ectopic formation of lymphoid follicles in the spinal cord (SC) at the injection site at all doses and the presence of granular material in neurons of the SC in high-dose animals. The granular material was seen in all the segments of the SC, but mainly in the lumbar segment and persisted at the end of the 26-week recovery period, while the lymphoid follicles showed a reversibility trend.

G3BP-driven RNP granules promote inhibitory RNA-RNA interactions resolved by DDX3X to regulate mRNA translatability.

Ribonucleoprotein (RNP) granules have been linked to translation regulation and disease, but their assembly and regulatory mechanisms are not well understood. Here, we show that the RNA-binding protein G3BP1 preferentially interacts with unfolded RNA, driving the assembly of RNP granule-like condensates that establish RNA-RNA interactions. These RNA-RNA interactions limit the mobility and translatability of sequestered mRNAs and stabilize the condensates.

Comparison of different methods for categorizing the individual susceptibility to motion sickness - A carsickness study.

In studies aimed at developing avoidance strategies to reduce motion sickness (kinetosis) in autonomous vehicles, failing to account for the wide variability in individual kinetosis susceptibility can lead to inaccuracies and disregard effective countermeasures. Three methods for assessing individual susceptibility to carsickness - two questionnaires focusing on kinetosis experiences and a kinetosis-provoking lab test - were compared with the development of kinetosis during real car driving tests. Questions about car-specific kinetosis-provoking situations (MS-C) exhibit stronger correlations with kinetosis in car experiments compared to the commonly used questions about kinetosis experiences across different types of transportation (MS-VD).

Agreement between self-, mother and father proxy-reports on health-related quality of life in adolescents with Tourette syndrome.

This study aimed to investigate agreement and discrepancies between parent proxy- and adolescent self-reports on assessments of adolescents' health-related quality of life (HRQoL), and the role that individual factors may play in parent-adolescent agreement, in a sample of adolescents with Tourette syndrome (TS) compared to a control group of healthy adolescents. Adolescents aged 12-18 years diagnosed with TS were recruited with their parents from primary and secondary referral centres. Adolescent healthy controls were matched for gender and age.

An automated single-molecule FRET platform for high-content, multiwell plate screening of biomolecular conformations and dynamics.

Single-molecule FRET (smFRET) has become a versatile tool for probing the structure and functional dynamics of biomolecular systems, and is extensively used to address questions ranging from biomolecular folding to drug discovery. Confocal smFRET measurements are amongst the widely used smFRET assays and are typically performed in a single-well format. Thus, sampling of many experimental parameters is laborious and time consuming.

Neurofilament Light Chain: A Translational Safety Biomarker for Drug-Induced Peripheral Neurotoxicity.

Branaplam is a splicing modulator previously under development as a therapeutic agent for Spinal Muscular Atrophy Type 1 and Huntington's disease. Branaplam increased the levels of survival motor neuron protein in preclinical studies and was well tolerated in early clinical studies; however, peripheral neurotoxicity was observed in a preclinical safety study in juvenile dogs. The aim of this study was to determine whether serum neurofilament light chain (NfL) concentrations in dogs could serve as a monitoring biomarker for branaplam-induced peripheral neurotoxicity.

A data-driven approach for modelling Karst spring discharge using transfer function noise models.

Karst aquifers are important sources of fresh water on a global scale. The hydrological modelling of karst spring discharge, however, still poses a challenge. In this study we apply a transfer function noise (TFN) model in combination with a bucket-type recharge model to simulate karst spring discharge.

Reliability and accuracy of single-molecule FRET studies for characterization of structural dynamics and distances in proteins.

Single-molecule Förster-resonance energy transfer (smFRET) experiments allow the study of biomolecular structure and dynamics in vitro and in vivo. We performed an international blind study involving 19 laboratories to assess the uncertainty of FRET experiments for proteins with respect to the measured FRET efficiency histograms, determination of distances, and the detection and quantification of structural dynamics. Using two protein systems with distinct conformational changes and dynamics, we obtained an uncertainty of the FRET efficiency ≤0.

Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome.

Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date.

Results of a Randomized Clinical Trial of Speech After Early Neurostimulation in Parkinson's Disease.

Background: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone.

Objective: This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN-DBS and BMT over 2 years, and secondary outcomes included non-speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician- and patient-reported assessments.

Methods: STN-DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation-for STN-DBS).