Evaluation of synaptotagmin-1 action models by all-atom molecular dynamics simulations.

Neurotransmitter release is triggered in microseconds by the two C domains of the Ca sensor synaptotagmin-1 and by SNARE complexes, which form four-helix bundles that bridge the vesicle and plasma membranes. The synaptotagmin-1 CB domain binds to the SNARE complex via a 'primary interface', but the mechanism that couples Ca-sensing to membrane fusion is unknown. Widespread models postulate that the synaptotagmin-1 Ca-binding loops accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers or helping bridge the membranes, but these models do not seem compatible with SNARE binding through the primary interface, which orients the Ca-binding loops away from the fusion site.

Increase of nitrous oxide-induced neurological disorders - a German multicenter experience.

Background: Nitrous oxide (N₂O), commonly known as laughing gas, is widely recognized for its anesthetic and analgesic effects, and is frequently used in medical contexts. However, its misuse can lead to significant neurological complications, which are often under-recognized in clinical practice. Recent data on such cases in Germany are rare.

Maximal mouth opening in infants and toddlers with spinal muscular atrophy: a prospective controlled study.

Background: Bulbar function is frequently impaired in patients with spinal muscular atrophy (SMA). Although extremely important for the patient's quality of life, it is difficult to address therapeutically. Due to bulbar dysfunction, maximum mouth opening (MMO) is suspected to be reduced in children with SMA.

Discontiguous recurrences of IDH-wildtype glioblastoma share a common origin with the initial tumor and are frequently hypermutated.

Glioblastoma is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after treatment. While most recurrences are local, patients rarely present with a new discontiguous focus of glioblastoma. Little is currently known about the genetic profile of discontiguous recurrences.

Sleep and circadian rhythms in delayed sleep-wake phase disorder: Phenotypic differences between patients with and without comorbid depression.

Delayed sleep-wake phase disorder involves chronic difficulty going to bed and waking up at conventional times and often co-occurs with depression. This study compared sleep and circadian rhythms between patients with delayed sleep-wake phase disorder with depression (DSWPD-D) and without (DSWPD-ND) comorbid depression. Clinical records of 162 patients with delayed sleep-wake phase disorder (70 DSWPD-D, 92 DSWPD-ND) were analysed, including a subset of 76 patients with circadian phase determined by the dim light melatonin onset.

Scale-up of CHO cell cultures: from 96-well-microtiter plates to stirred tank reactors across three orders of magnitude.

Background: For process development in mammalian cell cultivations, scale-up approaches are essential. A lot of studies concern the scale transfer between different-sized stirred tank reactors. However, process development usually starts in even smaller cultivation vessels like microtiter plates or shake flasks.

A rare haplotype of the GJD3 gene segregating in familial Meniere's disease interferes with connexin assembly.

Background: Familial Meniere's disease (FMD) is a rare polygenic disorder of the inner ear. Mutations in the connexin gene family, which encodes gap junction proteins, can also cause hearing loss, but their role in FMD is largely unknown.

Methods: We retrieved exome sequencing data from 94 individuals in 70 Meniere's disease (MD) families.

Context-dependent similarity analysis of analogue series for structure-activity relationship transfer based on a concept from natural language processing.

Analogue series (AS) are generated during compound optimization in medicinal chemistry and are the major source of structure-activity relationship (SAR) information. Pairs of active AS consisting of compounds with corresponding substituents and comparable potency progression represent SAR transfer events for the same target or across different targets. We report a new computational approach to systematically search for SAR transfer series that combines an AS alignment algorithm with context-depending similarity assessment based on vector embeddings adapted from natural language processing.

Comparison of whole genome sequencing performance from fish swabs and fin clips.

Objective: Fin clipping is the standard DNA sampling technique for whole genome sequencing (WGS) of small fish. The collection of fin clips requires anaesthesia or even euthanisation of the individual. Swabbing may be a less invasive, non-lethal alternative to fin-clipping.

Identification and characterization of tumor and stromal derived liquid biopsy analytes in pancreatic ductal adenocarcinoma.

Background: The lack of predictive biomarkers contributes notably to the poor outcomes of patients with pancreatic ductal adenocarcinoma (PDAC). Cancer-associated fibroblasts (CAFs) are the key components of the prominent PDAC stroma. Data on clinical relevance of CAFs entering the bloodstream, known as circulating CAFs (cCAFs) are scarce.

Effectiveness of workplace health promotion programs for industrial workers: a systematic review.

Background: Workplace health promotion is essential for individual and organisational well-being and disease prevention, also in industrial workers. As the transfer of the evidence on the effectiveness of such programs into practice is limited due to scattered effects, the need for a consolidation of the available studies is given. The purpose of this systematic review was to synthesise the evidence on the effectiveness of workplace health promotion programs for industrial workers.

Patient perspectives on stress after ICU and a short primary care based psychological intervention - results from a qualitative sub‑study of the PICTURE trial.

Background: Approximately 20-25% of patients who survive medical treatment at an intensive care unit (ICU) develop post-traumatic stress symptoms. There is currently a gap in follow-up care for them. As part of the PICTURE study, general practitioners (GPs) carried out a brief interview-based intervention.

Incidence of seroma and postoperative complications after breast surgery before and during the Covid-19 pandemic: results from a retrospective multicenter analysis.

Background: In recent years, there has been a growing number of case reports documenting delayed seroma in patients with a history of breast surgery and reconstruction. The occurrence of these seromas has been associated with prior SARS-CoV-2 infection or SARS-CoV-2 vaccination. So far, there are few systematic analyses on postoperative complications in breast surgery since the emergence of the SARS-CoV-2 pandemic.

Copper Tantalate by a Sodium-Driven Flux-Mediated Synthesis for Photoelectrochemical CO Reduction.

Copper-tantalate, CuTaO (CTO), shows significant promise as an efficient photocathode for multi-carbon compounds (C) production through photoelectrochemical (PEC) CO reduction, owing to its suitable energy bands and catalytic surface. However, synthesizing CTO poses a significant challenge due to its metastable nature and thermal instability. In this study, this challenge is addressed by employing a flux-mediated synthesis technique using a sodium-based flux to create sodium-doped CTO (Na-CTO) thin films, providing enhanced nucleation and stabilization for the CTO phase.

Quantitative Assessment of Microbial Transmission onto Environmental Surfaces Using Thermoresponsive Gelatin Hydrogels as a Finger Mimetic under In Situ-Mimicking Conditions.

Surface-mediated transmission of pathogens plays a key role in healthcare-associated infections. However, proper techniques for its quantitative analysis are lacking, making it challenging to develop novel antimicrobial and anti-fouling surfaces to reduce pathogen spread via environmental surfaces. This study demonstrates a gelatin hydrogel-based touch transfer test, the HydroTouch test, to evaluate pathogen transmission on high-touch surfaces under semi-dry conditions.

Small and medium-scale biorefineries: biomass quantification and its bioeconomic potential in the Southern Coastal Territory of Bahia.

Small and medium-scale biorefineries are processing facilities designed to produce a portfolio of value-added products with applications in different productive sectors. The Territory of the Southern Coast (TSC) of Bahia in Brazil has a high potential to provide agricultural and forest biomass for these bioindustries. This study focuses on quantifying the biomass of key agricultural crops in the TSC from 1999 to 2019, utilizing data from the Municipal Agricultural Production (MAP) survey conducted by the Brazilian Institute of Geography and Statistics (IBGE).

Resolving tissue complexity by multimodal spatial omics modeling with MISO.

Spatial molecular profiling has provided biomedical researchers valuable opportunities to better understand the relationship between cellular localization and tissue function. Effectively modeling multimodal spatial omics data is crucial for understanding tissue complexity and underlying biology. Furthermore, improvements in spatial resolution have led to the advent of technologies that can generate spatial molecular data with subcellular resolution, requiring the development of computationally efficient methods that can handle the resulting large-scale datasets.

Biomechanical simulation of bed turning post-acetabular fracture fixation.

Before patients begin out-of-bed exercises following internal fixation surgery for acetabular fractures, turning over in bed serves as a crucial intervention to mitigate complications associated with prolonged bed rest. However, data on the safety of this maneuver post-surgery are limited, and the biomechanical evidence remains unclear. This study aims to introduce a novel loading protocol designed to preliminarily simulate the action of turning over in bed and to compare the biomechanical properties of two fixation methods for acetabular fractures under this new protocol.

Autophagy regulator ATG5 preserves cerebellar function by safeguarding its glycolytic activity.

Dysfunctions in autophagy, a cellular mechanism for breaking down components within lysosomes, often lead to neurodegeneration. The specific mechanisms underlying neuronal vulnerability due to autophagy dysfunction remain elusive. Here we show that autophagy contributes to cerebellar Purkinje cell (PC) survival by safeguarding their glycolytic activity.

Choroid plexus volume is enlarged in long COVID and associated with cognitive and brain changes.

Patients with post-COVID condition (PCC) present with diverse symptoms which persist at long-term after SARS-CoV-2 infection. Among these symptoms, cognitive impairment is one of the most prevalent and has been related to brain structural and functional changes. The underlying mechanisms of these cognitive and brain alterations remain elusive but neuroinflammation and immune mechanisms have been majorly considered.