Investigating Complexin-Membrane Interactions Using NMR and Optical Methods.

Complexins are a family of small presynaptic proteins that regulate neurotransmitter release at nerve terminals and are highly conserved in evolution. While direct interactions with SNARE proteins are critical for all complexin functions, binding of their disordered C-terminal domains (CTD) to membranes, especially to synaptic vesicle membranes, is essential for the ability of complexin to inhibit vesicle release. Furthermore, while some complexin CTDs possess an endogenous affinity for membranes, other complexin isoforms are subject to lipidation at their C-termini, which is presumed to confer additional membrane binding.

The Potential of Polymers and Glass to Enhance Hydrogen Storage Capacity: A Mathematical Approach.

This manuscript contributes to understanding the role of hydrogen in different materials, emphasizing polymers and composite materials, to increase hydrogen storage capacity in those materials. Hydrogen storage is critical in advancing and optimizing sustainable energy solutions that are essential for improving their performance. Capillary arrays, which offer increased surface area and optimized storage geometries, present a promising avenue for enhancing hydrogen uptake.

Amyloid fibril structures link CHCHD10 and CHCHD2 to neurodegeneration.

CHCHD10 is mutated in rare cases of FTD and ALS and aggregates in mouse models of disease. Here we show that the disordered N-terminal domain of CHCHD10 forms amyloid fibrils and report their cryoEM structure. Disease-associated mutations cannot be accommodated by the WT fibril structure, while sequence differences between CHCHD10 and CHCHD2 are tolerated, explaining the co-aggregation of the two proteins and linking CHCHD10 and CHCHD2 amyloid fibrils to neurodegeneration.

Control of G protein-coupled receptor function via membrane-interacting intrinsically disordered C-terminal domains.

G protein-coupled receptors (GPCRs) control intracellular signaling cascades via agonist-dependent coupling to intracellular transducers including heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. In addition to their critical interactions with the transmembrane core of active GPCRs, all three classes of transducers have also been reported to interact with receptor C-terminal domains (CTDs). An underexplored aspect of GPCR CTDs is their possible role as lipid sensors given their proximity to the membrane.

Carbon dots as dual inhibitors of tau and amyloid-beta aggregation for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of senile dementia, presenting a significant challenge for the development of effective treatments. AD is characterized by extracellular amyloid plaques and intraneuronal neurofibrillary tangles. Therefore, targeting both hallmarks through inhibition of amyloid beta (Aβ) and tau aggregation presents a promising approach for drug development.

Alpha synuclein modulates mitochondrial Ca uptake from ER during cell stimulation and under stress conditions.

Alpha synuclein (a-syn) is an intrinsically disordered protein prevalent in neurons, and aggregated forms are associated with synucleinopathies including Parkinson's disease (PD). Despite the biomedical importance and extensive studies, the physiological role of a-syn and its participation in etiology of PD remain uncertain. We showed previously in model RBL cells that a-syn colocalizes with mitochondrial membranes, depending on formation of N-terminal helices and increasing with mitochondrial stress.

Control of G protein-coupled receptor function via membrane-interacting intrinsically disordered C-terminal domains.

G protein-coupled receptors (GPCRs) control intracellular signaling cascades via agonist-dependent coupling to intracellular transducers including heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. In addition to their critical interactions with the transmembrane core of active GPCRs, all three classes of transducers have also been reported to interact with receptor C-terminal domains (CTDs). An underexplored aspect of GPCR CTDs is their possible role as lipid sensors given their proximity to the membrane.

Feasibility and acceptability of a new web-based cognitive training platform for cognitively healthy older adults: the breakfast task.

Background: Developing efficient cognitive training for the older population is a major public health goal due to its potential cognitive benefits. A promising training target is executive control, critical for multitasking in everyday life. The aim of this pilot study was to establish the feasibility and acceptability of the Breakfast Task training in older adults, a new web-based cognitive training platform that simulates real-life multitasking demands.

Structure and DNA-bridging activity of the essential Rec114-Mei4 trimer interface.

The DNA double-strand breaks (DSBs) that initiate meiotic recombination are formed by an evolutionarily conserved suite of factors that includes Rec114 and Mei4 (RM), which regulate DSB formation both spatially and temporally. In vivo, these proteins form large immunostaining foci that are integrated with higher-order chromosome structures. In vitro, they form a 2:1 heterotrimeric complex that binds cooperatively to DNA to form large, dynamic condensates.

Alpha Synuclein Modulates Mitochondrial Ca Uptake from ER During Cell Stimulation and Under Stress Conditions.

Alpha synuclein (a-syn) is an intrinsically disordered protein prevalent in neurons, and aggregated forms are associated with synucleinopathies including Parkinson' disease (PD). Despite the biomedical importance and extensive studies, the physiological role of a-syn and its participation in etiology of PD remain uncertain. We showed previously in model RBL cells that a-syn colocalizes with mitochondrial membranes, depending on formation of N-terminal helices and increasing with mitochondrial stress.

Structure and DNA bridging activity of the essential Rec114â€"Mei4 trimer interface.

The DNA double-strand breaks (DSBs) that initiate meiotic recombination are formed by an evolutionarily conserved suite of factors that includes Rec114 and Mei4 (RM), which regulate DSB formation both spatially and temporally. , these proteins form large immunostaining foci that are integrated with higher order chromosome structures. , they form a 2:1 heterotrimeric complex that binds cooperatively to DNA to form large, dynamic condensates.

The Role of Membrane Affinity and Binding Modes in Alpha-Synuclein Regulation of Vesicle Release and Trafficking.

Alpha-synuclein is a presynaptic protein linked to Parkinson's disease with a poorly characterized physiological role in regulating the synaptic vesicle cycle. Using RBL-2H3 cells as a model system, we earlier reported that wild-type alpha-synuclein can act as both an inhibitor and a potentiator of stimulated exocytosis in a concentration-dependent manner. The inhibitory function is constitutive and depends on membrane binding by the helix-2 region of the lipid-binding domain, while potentiation becomes apparent only at high concentrations.

Proline-Rich Region II (PRR2) Plays an Important Role in Tau-Glycan Interaction: An NMR Study.

(1) Background: Prion-like transcellular spreading of tau pathology in Alzheimer's disease (AD) is mediated by tau binding to the cell-surface glycan heparan sulfate (HS). However, the structural determinants for tau-HS interaction are not well understood. (2) Methods and Results: Binding-site mapping using NMR showed two major binding regions in full-length tau responsible for heparin interaction.

Molecular and functional interactions of alpha-synuclein with Rab3a.

Alpha-synuclein (a-Syn) is a presynaptic protein, the misfolding of which is associated with Parkinson's disease. Rab GTPases are small guanine nucleotide binding proteins that play key roles in vesicle trafficking and have been associated with a-Syn function and dysfunction. a-Syn is enriched on synaptic vesicles, where it has been reported to interact with GTP-bound Rab3a, a master regulator of synaptic vesicle trafficking.

Membrane Binding Induces Distinct Structural Signatures in the Mouse Complexin-1C-Terminal Domain.

Complexins play a critical role in regulating SNARE-mediated exocytosis of synaptic vesicles. Evolutionary divergences in complexin function have complicated our understanding of the role these proteins play in inhibiting the spontaneous fusion of vesicles. Previous structural and functional characterizations of worm and mouse complexins have indicated the membrane curvature-sensing C-terminal domain of these proteins is responsible for differences in inhibitory function.

Optimising the management of children with concomitant bladder dysfunction and behavioural disorders.

Bladder dysfunction and behavioural disorders in children are commonly concomitant; hence, it is difficult to treat each in isolation. Pharmacotherapy is common treatment for behavioural disorders, and these medications may have intended or unintended positive or negative bladder sequelae. This review identifies the literature regarding the effects of behavioural pharmacotherapy on bladder functioning and possible bladder management strategies in children with concomitant behaviour and bladder disorders to enable clinicians to better manage both conditions.

Synthesis of Refractory High-Entropy Alloy WTaMoNbV by Powder Bed Fusion Process Using Mixed Elemental Alloying Powder.

The growing interest in refractory high-entropy alloys (HEAs) in the last decade is mainly due to their thermal stability, outstanding mechanical properties, and excellent corrosion resistance. However, currently HEAs are still not considered for use as common structural materials due to their inherent drawbacks in terms of processing and machining operations. The recent progress witnessed in additive manufacturing (AM) technologies has raised the option of producing complex components made of HEAs with minimal machining processes.

Imposed load versus voluntary investment: Executive control and attention management in dual-task performance.

Dual task performance is one of the most frequently used paradigm in the evaluation of coping with concurrent task demands. The Breakfast Task experimented in this paper, was originally developed as a general indicator of coping ability with high demand executive control and attention management requirements. It is a computer-based simulation, in which the performer is required to cook several food items while concurrently setting table for guests.

Synaptic vesicle binding of α-synuclein is modulated by β- and γ-synucleins.

α-synuclein, β-synuclein, and γ-synuclein are abundantly expressed proteins in the vertebrate nervous system. α-synuclein functions in neurotransmitter release by binding to and clustering synaptic vesicles and chaperoning SNARE-complex assembly. Pathologically, aggregates originating from soluble pools of α-synuclein are deposited into Lewy bodies in Parkinson's disease and related synucleinopathies.