Exploring the druggability of the UEV domain of human TSG101 in search for broad-spectrum antivirals.

The ubiquitin E2 variant domain of TSG101 (TSG101-UEV) plays a pivotal role in protein sorting and virus budding by recognizing PTAP motifs within ubiquitinated proteins. Disruption of TSG101-UEV/PTAP interactions has emerged as a promising strategy for the development of host-oriented broad-spectrum antivirals with low susceptibility to resistance. TSG101 is a challenging target characterized by an extended and flat binding interface, low affinity for PTAP ligands, and complex binding energetics.

The Impact of Non-trauma Factors on Trauma Patient Mortality and Hospital Resource Utilization: Population-Based Retrospective Review.

Background: The death of trauma patients with low injury severity scores (ISS) may not be fully explained by the severity of their injuries. Our objective was to evaluate preexisting conditions (PECs) that may contribute to the mortality rate of and hospital resources consumed by patients with low ISS.

Methods: Trauma patients with ISS <9 were selected from the National Trauma Database Bank [NTDB] [2019-21].

Knowledge, perception and attitude about Crimean-Congo Haemorrhagic Fever (CCHF) among veterinary students and professionals of Spain.

The Crimean-Congo haemorrhagic fever (CCHF) is a tropical viral zoonosis first reported in Spain with 17 detected cases since 2010-2024. Health professionals, including veterinarians, play a crucial role in controlling and preventing this disease. This study aimed to analyse and compare the knowledge, perceptions, and attitudes of veterinary students and professionals in Spain regarding CCHF and zoonoses in general.

Post-Antibiotic and Post-Antibiotic Sub-Minimum Inhibitory Concentration Effects of Carvacrol against Typhimurium.

Carvacrol is a compound present in essential oils with proven antimicrobial activity against numerous pathogens. We firstly determine the post-antibiotic effect (PAE) of carvacrol (1×, 2×, 4× MIC) and post-antibiotic sub-minimum inhibitory concentration (MIC) effect (1× + 0.25× MIC and 2× + 0.

Phage display identification of high-affinity ligands for human TSG101-UEV: A structural and thermodynamic study of PTAP recognition.

The ubiquitin E2 variant domain of TSG101 (TSG101-UEV) plays a pivotal role in protein sorting and virus budding by recognizing PTAP motifs within ubiquitinated proteins. Disrupting TSG101-UEV/PTAP interactions has emerged as a promising strategy for the development of novel host-oriented antivirals with a broad spectrum of action. Nonetheless, finding inhibitors with good properties as therapeutic agents remains a challenge since the key determinants of binding affinity and specificity are still poorly understood.

Morbidity and Mortality of Trauma Patients 55 and Older: A Study of Nontrauma Risk Factors.

The American College of Surgeons (ACS) recommends that special considerations be made during triage of trauma patients aged ≥55 due to an observed increase in morbidity and mortality in this population. The geriatric population aged ≥65 represents 30% of all trauma patients. Our objective was to assess which pre-existing conditions (PECs) are associated with worse outcomes in trauma patients aged ≥55.

Monastrol suppresses invasion and metastasis in human colorectal cancer cells by targeting fascin independent of kinesin-Eg5 pathway.

Rearrangement of the actin cytoskeleton is a prerequisite for carcinoma cells to develop cellular protrusions, which are required for migration, invasion, and metastasis. Fascin is a key protein involved in actin bundling and is expressed in aggressive and invasive carcinomas. Additionally, fascin appears to be involved in tubulin-binding and microtubule rearrangement.

Direct interaction between marine cyanobacteria mediated by nanotubes.

Microbial associations and interactions drive and regulate nutrient fluxes in the ocean. However, physical contact between cells of marine cyanobacteria has not been studied thus far. Here, we show a mechanism of direct interaction between the marine cyanobacteria and , the intercellular membrane nanotubes.

Enhancing MD simulations: ASGARD's automated analysis for GROMACS.

Molecular Dynamics (MD) simulations are essential in analyzing the physical movement of molecules, with GROMACS being a widely recognized open-source package for this purpose. However, conducting analyses individually in GROMACS can take excessive time and effort. Addressing this challenge, we introduce ASGARD, an innovative workflow designed to streamline and automate the analysis of MD simulation of protein or protein-ligand complex.

Emergency Surgical Treatment and Triage: Targeting Optimal Outcomes for Emergency Surgical Patients From Index Encounter Through Definitive Care.

Background: Patients with emergency surgical conditions (ESCs) experience higher complication rates than those without emergency conditions. Our purpose was to improve time-based key performance indicators (KPIs) of care for ESC patients, including diagnostic workup, empiric stabilization, and referral to definitive care.

Methods: A rapid response program (ESTAT) was developed to screen for and coordinate optimal, timely care for a spectrum of high-risk ESCs, from the patient's index clinical encounter up to definitive care.

Droplet digital PCR as alternative to microbiological culture for complex detection in bovine lymph node tissue samples.

Introduction: Bovine tuberculosis (bTB) caused by complex (MTC) remains a significant concern for public health. Direct real-time PCR and droplet digital PCR (ddPCR) are proposed as alternative tools to enhance diagnostic precision and efficiency. This study aims to assess the diagnostic performance of a ddPCR assay targeting IS for the detection of MTC DNA in both microbiological culture and fresh lymph node (LN) tissue samples obtained from cattle, in comparison with the established reference standard, the microbiological culture followed by real-time PCR.

An ancient bacterial zinc acquisition system identified from a cyanobacterial exoproteome.

Bacteria have developed fine-tuned responses to cope with potential zinc limitation. The Zur protein is a key player in coordinating this response in most species. Comparative proteomics conducted on the cyanobacterium Anabaena highlighted the more abundant proteins in a zur mutant compared to the wild type.

FurC (PerR) contributes to the regulation of peptidoglycan remodeling and intercellular molecular transfer in the cyanobacterium sp. strain PCC 7120.

Microbial extracellular proteins and metabolites provide valuable information concerning how microbes adapt to changing environments. In cyanobacteria, dynamic acclimation strategies involve a variety of regulatory mechanisms, being ferric uptake regulator proteins as key players in this process. In the nitrogen-fixing cyanobacterium sp.

Evaluation of the diagnostic accuracy of the serological test for paratuberculosis in cattle according to tuberculosis status.

Background: Enzyme-linked immunosorbent assays (ELISAs) are the most widely used diagnostic tools in bovine paratuberculosis (bPTB) control. However, their diagnostic accuracy may be compromised by bovine tuberculosis (bTB) infection, as both diseases share diagnostic targets.

Methods: The bPTB and bTB infection status of 228 animals was determined using microbiological tissue culture as a reference test.

Optimization of real-time PCR protocols from lymph node bovine tissue for direct detection of complex.

Bovine tuberculosis (bTB) is a zoonotic disease and a global health problem that is subjected to obligatory eradication programs in the European Union. Microbiological culture is an imperfect technique for bTB diagnosis. This study aims to compare and validate two DNA isolation protocols and three different specific DNA targets, IS6110, IS4, and mpb70, to confirm complex (MTC) infection by real-time PCR directly from fresh tissue samples.

Detection of complex field infections in cattle using fecal volatile organic compound analysis through gas chromatography-ion mobility spectrometry combined with chemometrics.

Bovine tuberculosis is considered a re-emerging disease caused by different species from the complex (MTC), important not only for the livestock sector but also for public health due to its zoonotic character. Despite the numerous efforts that have been carried out to improve the performance of the current diagnostic procedures, nowadays, they still pose several drawbacks, such as moderate to low sensitivity, highlighting the necessity to develop alternative and innovative tools to complement control and surveillance frameworks. Volatilome analysis is considered an innovative approach which has been widely employed in animal science, including animal health field and diagnosis, due to the useful and interesting information provided by volatile metabolites.

SepT, a novel protein specific to multicellular cyanobacteria, influences peptidoglycan growth and septal nanopore formation in sp. PCC 7120.

Multicellular organization is a requirement for the development of complex organisms, and filamentous cyanobacteria such as represent a paradigmatic case of bacterial multicellularity. The filament can include hundreds of communicated cells that exchange nutrients and regulators and, depending on environmental conditions, can include different cell types specialized in distinct biological functions. Hence, the specific features of the filament and how they are propagated during cell division represent outstanding biological issues.

Diagnostic performance of faecal and tissue multiplex qPCR IS900/F57 for the detection of Mycobacterium avium subspecies paratuberculosis in cattle.

Mycobacterium avium subspecies paratuberculosis (MAP) is responsible for bovine-paratuberculosis (bPTB), which causes high production losses in cattle. A cross-sectional study was conducted in 228 cattle to evaluate the validity and diagnostic utility of a multiplex real-time PCR (qPCR) on faecal and intestinal samples [ileocaecal valve (ICV) and ileocaecal lymph nodes (ICLN)], using intestinal tissue culture as a reference test. Based on the sensitivity, specificity, and likelihood ratios (LR) obtained, the diagnostic value of faecal qPCR for confirming MAP infection was moderate (sensitivity 50.

A calorimetric and structural analysis of cooperativity in the thermal unfolding of the PDZ tandem of human Syntenin-1.

Syntenin-1 is a multidomain protein containing a central tandem of two PDZ domains flanked by two unnamed domains. Previous structural and biophysical studies show that the two PDZ domains are functional both isolated and in tandem, occurring a gain in their respective binding affinities when joined through its natural short linker. To get insight into the molecular and energetic reasons of such a gain, here, the first thermodynamic characterization of the conformational equilibrium of Syntenin-1 is presented, with special focus on its PDZ domains.

Real-world discontinuations due to neuropsychiatric symptoms in people living with HIV treated with second-generation integrase inhibitors: a systematic review.

Introduction: Second-generation integrase strand transfer inhibitors such as bictegravir (BIC) and dolutegravir (DTG) are the standard of care for starting therapy in people living with HIV (PLHIV). However, their use has been associated with neuropsychiatric symptoms (NPSs) that may lead to treatment discontinuation. We aim to describe and synthesize information on safety and discontinuation rates and to summarize potential risk factors associated with the development of NPSs in PLHIV treated with these regimens.