Structural Dynamics of SNARE Complex Assembly in the Ribbon Synapses Observed by smFRET.

Single-molecule fluorescence resonance energy transfer (smFRET) is a powerful technique for studying the structural dynamics of protein molecules or detecting interactions between protein molecules in real time. Due to the high sensitivity in spatial and temporal resolution, smFRET can decipher sub-populations within heterogeneous native state conformations, which are generally lost in traditional measurements due to ensemble averaging. In addition, the single-molecule reconstitution allows protein molecules to be observed for an extensive period of time and can recapitulate the geometry of the cellular environment to retain biological function.

Transcorneal aspiration for management of primary iris cysts in the standing horse.

Background: Equine primary iris cysts are usually incidental findings but, if associated with clinical signs, may require intervention. The use of laser (Nd:Yag or diode) has been reported but requires specialised equipment. Transcorneal aspiration has not been previously evaluated in the standing horse.

Use of recombinant tissue plasminogen activator (rTPA) for treatment of fibrin in the anterior chamber of the horse.

Background: Recombinant intracameral tissue plasminogen activator (rTPA) administration can aid clearance of fibrin from the anterior chamber.

Materials And Methods: In this retrospective multicentre case series, the effect of intracameral rTPA administration to treat fibrin in the anterior chamber resulting from trauma or inflammatory ocular disease was evaluated. Clinical data from 30 treatments in 29 horses were obtained from medical records from 2003 to 2022.

BEVA primary care clinical guidelines: Equine parasite control.

Background: There is a lack of consensus on how best to balance our need to minimise the risk of parasite-associated disease in the individual horse, with the need to limit the use of anthelmintics in the population to preserve their efficacy through delaying further development of resistance.

Objectives: To develop evidence-based guidelines utilising a modified GRADE framework.

Methods: A panel of veterinary scientists with relevant expertise and experience was convened.

The Use of Biologics in NFL Athletes: An Expert Consensus of NFL Team Physicians.

Background: There is a lack of published information outlining the use of biologics in National Football League (NFL) athletes and limited data to guide biologic treatment strategies.

Purpose: To develop a consensus on the use of biologics among NFL team physicians.

Study Design: Consensus statement.

Different Forms of Disorder in NMDA-Sensitive Glutamate Receptor Cytoplasmic Domains Are Associated with Differences in Condensate Formation.

The N-methyl-D-aspartate (NMDA)-sensitive glutamate receptor (NMDAR) helps assemble downstream signaling pathways through protein interactions within the postsynaptic density (PSD), which are mediated by its intracellular C-terminal domain (CTD). The most abundant NMDAR subunits in the brain are GluN2A and GluN2B, which are associated with a developmental switch in NMDAR composition. Previously, we used single molecule fluorescence resonance energy transfer (smFRET) to show that the GluN2B CTD contained an intrinsically disordered region with slow, hop-like conformational dynamics.

Fuzzy supertertiary interactions within PSD-95 enable ligand binding.

The scaffold protein PSD-95 links postsynaptic receptors to sites of presynaptic neurotransmitter release. Flexible linkers between folded domains in PSD-95 enable a dynamic supertertiary structure. Interdomain interactions within the PSG supramodule, formed by DZ3, H3, and uanylate Kinase domains, regulate PSD-95 activity.

An objective study into the effects of an incline on naturally occurring lameness in horses.

Background: The clinical examination of lame horses in real world settings often requires the use of sloped surfaces.

Objectives: This pilot study aimed to evaluate the effects of uphill and downhill locomotion on asymmetry in horses with naturally occurring lameness affecting forelimbs and hindlimbs.

Methods: Ten horses (8-19 years) with forelimb lameness and eight horses (7-16 years) with hindlimb lameness were fitted with inertial sensors at the poll, withers, sacrum and both tuber coxae.

Conformational change of Syntaxin-3b in regulating SNARE complex assembly in the ribbon synapses.

Neurotransmitter release of synaptic vesicles relies on the assembly of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, consisting of syntaxin and SNAP-25 on the plasma membrane and synaptobrevin on the synaptic vesicle. The formation of the SNARE complex progressively zippers towards the membranes, which drives membrane fusion between the plasma membrane and the synaptic vesicle. However, the underlying molecular mechanism of SNARE complex regulation is unclear.

Structure and conformational dynamics of toxin A.

toxin A and B (TcdA and TcdB) are two major virulence factors responsible for diseases associated with infection (CDI). Here, we report the 3.18-Å resolution crystal structure of a TcdA fragment (residues L843-T2481), which advances our understanding of the complete structure of TcdA holotoxin.

Resilience of terrestrial and aquatic fauna to historical and future wildfire regimes in western North America.

Wildfires in many western North American forests are becoming more frequent, larger, and severe, with changed seasonal patterns. In response, coniferous forest ecosystems will transition toward dominance by fire-adapted hardwoods, shrubs, meadows, and grasslands, which may benefit some faunal communities, but not others. We describe factors that limit and promote faunal resilience to shifting wildfire regimes for terrestrial and aquatic ecosystems.

Probing Interdomain Linkers and Protein Supertertiary Structure In Vitro and in Live Cells with Fluorescent Protein Resonance Energy Transfer.

Many proteins are composed of independently-folded domains connected by flexible linkers. The primary sequence and length of such linkers can set the effective concentration for the tethered domains, which impacts rates of association and enzyme activity. The length of such linkers can be sensitive to environmental conditions, which raises questions as to how studies in dilute buffer relate to the highly-crowded cellular environment.

Mixed methods investigation of the use of telephone triage within UK veterinary practices for horses with abdominal pain: A Participatory action research study.

Background: Telephone triage is an integral part of modern patient care systems in human medicine, and a key component of veterinary practice care systems. There is currently no published research on telephone triage within the veterinary profession.

Objective: To investigate current approaches to telephone triage of horses with abdominal pain (colic) in veterinary practice and develop new resources to support decision-making.

The complexity of clinically-normal sinus-rhythm ECGs is decreased in equine athletes with a diagnosis of paroxysmal atrial fibrillation.

Equine athletes have a pattern of exercise which is analogous to human athletes and the cardiovascular risks in both species are similar. Both species have a propensity for atrial fibrillation (AF), which is challenging to detect by ECG analysis when in paroxysmal form. We hypothesised that the proarrhythmic background present between fibrillation episodes in paroxysmal AF (PAF) might be detectable by complexity analysis of apparently normal sinus-rhythm ECGs.

Use of smartphones to aid the teaching of equine ocular fundus examination.

Background: Teaching and learning how to perform examination of the ocular fundus is challenging. Smartphones can support to enhance students' confidence and experience.

Methods: Following an optional year-4 ophthalmoscopy practical using hand-held ophthalmoscopes, students completed a questionnaire using a visual analogue scale (VAS) investigating if students felt smartphone use aided learning and if student's self-assessed confidence in visualising the ocular fundus had improved.

Structure of the full-length Clostridium difficile toxin B.

Clostridium difficile is an opportunistic pathogen that establishes in the colon when the gut microbiota are disrupted by antibiotics or disease. C. difficile infection (CDI) is largely caused by two virulence factors, TcdA and TcdB.

Spontaneous Switching among Conformational Ensembles in Intrinsically Disordered Proteins.

The common conception of intrinsically disordered proteins (IDPs) is that they stochastically sample all possible configurations driven by thermal fluctuations. This is certainly true for many IDPs, which behave as swollen random coils that can be described using polymer models developed for homopolymers. However, the variability in interaction energy between different amino acid sequences provides the possibility that some configurations may be strongly preferred while others are forbidden.

Cardiac Therapeutics in Horses.

Many cardiac therapeutics lack significant evidence of benefit in the horse, and in many cases their use is based on extrapolation of evidence from other species. In recent years there has been a push to develop a better understanding of both the pharmacodynamics and pharmacokinetics of these drugs. Recent data have described the use of antiarrhythmic agents including sotalol, flecainide, and amiodarone.

The application of Lempel-Ziv and Titchener complexity analysis for equine telemetric electrocardiographic recordings.

The analysis of equine electrocardiographic (ECG) recordings is complicated by the absence of agreed abnormality classification criteria. We explore the applicability of several complexity analysis methods for characterization of non-linear aspects of electrocardiographic recordings. We here show that complexity estimates provided by Lempel-Ziv '76, Titchener's T-complexity and Lempel-Ziv '78 analysis of ECG recordings of healthy Thoroughbred horses are highly dependent on the duration of analysed ECG fragments and the heart rate.

A viral-fusion-peptide-like molecular switch drives membrane insertion of botulinum neurotoxin A1.

Botulinum neurotoxin (BoNT) delivers its protease domain across the vesicle membrane to enter the neuronal cytosol upon vesicle acidification. This process is mediated by its translocation domain (H), but the molecular mechanism underlying membrane insertion of H remains poorly understood. Here, we report two crystal structures of BoNT/A1 H that reveal a novel molecular switch (termed BoNT-switch) in H, where buried α-helices transform into surface-exposed hydrophobic β-hairpins triggered by acidic pH.

Management factors and clinical implications of glandular and squamous gastric disease in horses.

Background: To date, risk factors for equine glandular gastric disease (EGGD) have not been described in Thoroughbred racehorses.

Objectives: To determine management factors associated with EGGD, identify clinical signs in affected horses, and compare these to equine squamous gastric disease (ESGD).

Animals: The study was carried out on 109 Thoroughbred racehorses from 8 training yards (3 in the United Kingdom and 5 in Australia).

Publisher Correction: Precision and accuracy of single-molecule FRET measurements-a multi-laboratory benchmark study.

This paper was originally published under standard Springer Nature copyright. As of the date of this correction, the Analysis is available online as an open-access paper with a CC-BY license. No other part of the paper has been changed.