bluuebunny/crossref_metadata_2025_split huggingface dataset:
EnteropathogenicEscherichia coliinducesEntamoeba histolyticaLévy-like movement on fibronectin-rich substrate by reducing traction forces
Authors: Guo Yuanning , Ye Jun , Odeh Anas , Trebicz-Geffen Meirav , Wolfenson Haguy , Ankri Serge 
Published: September 2024

AbstractAmebiasis, caused byEntamoeba histolytica, is a global health concern, affecting millions and causing significant mortality, particularly in areas with poor sanitation. Although recent studies have examinedE. histolytica’s interaction with human intestinal microbes, the impact of bacterial presence on the parasite’s motility, mechanical forces, and their potential role in altering invasiveness have not been fully elucidated. In this study, we utilized a micropillar-array system combined with live imaging to investigate the effects of enteropathogenicEscherichia colionE. histolytica’s motility characteristics, F-actin spatial localization, and traction force exerted on fibronectin-coated substrates. Our findings indicate that co-incubation withE. colisignificantly enhances the motility ofE. histolytica, as evidenced by the enhancement of Lévy-like movement patterns, i.e., increased directionality and velocity. This increased motility is accompanied by a reduction in F-actin-dependent traction forces and podosome-like structures on fibronectin-coated substrates, but with increased F-actin localization in the upper part of the cytoplasm. These findings highlight the role of physical interactions and cellular behaviors in modulating the parasite’s virulence, providing new insights into the mechanistic basis of its pathogenicity.Author SummaryAmebiasis, caused by the protozoan parasiteEntamoeba histolytica, is a major global health issue, affecting around 50 million people and resulting in 100,000 deaths annually. The disease is transmitted through contaminated food and water. Upon reaching the intestines, which are teeming with bacteria,E. histolyticabegins its invasion by removing the protective mucus layer, followed by adhering to and detaching enterocytes, leading to the disruption and degradation of the epithelial barrier. Afterwards,E. histolyticainvades along the fibronectin-rich basement membrane deep into the crypts of Lieberkühn, eventually penetrating the fibronectin- rich lamina propria. This leads to further tissue destruction and potential dissemination to distant organs, causing severe complications. In our study, we explored how the presence of enteropathogenic bacteria affects the parasite’s motility and mechanical force generation, both of which are key to its pathogenicity. Using a micropillar-array system and live imaging, we found that exposure to enteropathogenicEscherichia colisignificantly increasesE. histolytica’s motility while reducing its traction force on fibronectin-rich matrices. These changes in behavior highlight the role of bacterial interactions in enhancing the parasite’s virulence. Our findings provide important insights into the mechanistic basis ofE. histolytica’s pathogenicity, offering potential avenues for new treatments against amebiasis.
Self-immunity towards a novel competence-induced streptococcal murein hydrolase is mediated by a Fem-transferase-like protein
Authors: Mårli Marita Torrissen , Arntzen Magnus Øverlie , Allred Jennie Ann , Schultheiss Anna Teigen , Oppegaard Oddvar , Kjos Morten , Straume Daniel 
Published: September 2024

AbstractMurein hydrolases (or peptidoglycan hydrolases) play diverse roles in bacteria, from controlled remodeling of the bacterial cell wall to lytic agents. In streptococci, a subset of these hydrolases is associated with competence-induced fratricide, a process where bacteria kill closely related cells to release DNA that can be taken up during natural transformation. Here, we characterize ScrM, a competence-induced murein hydrolase fromStreptococcus dysgalactiaecomprising a CHAP domain, an SH3b domain and an uncharacterized C-terminal domain (CCD). ScrM displayed lytic activity against pyogenic and salivarius group streptococci. Microscopy analysis of fluorescent fusions revealed that ScrM specifically localizes to the division zone of sensitive cells, with binding and localization mediated primarily by CCD. Upon competence induction, cells became immune to ScrM due to expression of ScrI, a Fem-transferase-like protein. We show by LC-MS/MS that ScrI incorporates Thr in place of Ala into the interpeptide bridges of peptidoglycan, which in turn prevents ScrM binding to the division zone, thereby protecting the cells from self-lysis during competence. ScrM and ScrI are conserved among pyogenic streptococcal pathogens and represent new players in the cell wall biogenesis of these bacteria that may form a platform for development of novel antimicrobial strategies.
Evaluation of antibacterial activity of ethanolic extracts ofRuta chalepensis, Hippocratea excelsa, Litsea glaucescensandWaltheria americanaagainst methicillin-resistantStaphylococcus aureus
Authors: Salvador Martínez Margarita , Fuentes Gutiérrez José Fernando , Tescucano Alonso Alonso Rubén , Martínez González Gabriel 
Published: September 2024

AbstractAntimicrobial resistance is still a problem today, with increasingly limited therapeutic options.Staphylococcus aureuscauses infections of the skin, soft tissues and contains a high degree of pathogenicity. The objective of this work was to determine the antibacterial activity of ethanol extracts from several plants at different concentrations against strains ofStaphylococcus aureusresistant and sensitive to methicillin, using the Kirby-Bauer method. The ethanolic extract of Rue (Ruta chalepensis) shows a significantly higher antibacterial activity than the extracts of Cancerina (Hippocratea excelsa), Laurel (Litsea glaucescens) and Tapacola (Waltheria americana) alone and in combination. Phenolic compounds, anthocyanins and flavonoids were determined. Rue may contribute to the potential identification of a natural alternative therapy against methicillin resistantStaphylococcus aureus.
Unified Sampling and Ranking for Protein Docking with DFMDock
Authors: Chu Lee-Shin , Sarma Sudeep , Gray Jeffrey J. 
Published: September 2024

AbstractDiffusion models have shown promise in addressing the protein docking problem. Traditionally, these models are used solely for sampling docked poses, with a separate confidence model for ranking. We introduce DFMDock (Denoising Force Matching Dock), a diffusion model that unifies sampling and ranking within a single framework. DFMDock features two output heads: one for predicting forces and the other for predicting energies. The forces are trained using a denoising force matching objective, while the energy gradients are trained to align with the forces. This design enables our model to sample using the predicted forces and rank poses using the predicted energies, thereby eliminating the need for an additional confidence model. Our approach outperforms the previous diffusion model for protein docking, DiffDock-PP, with a sampling success rate of 44% compared to its 8%, and a Top-1 ranking success rate of 16% compared to 0% on the Docking Benchmark 5.5 test set. In successful decoy cases, the DFMDock Energy forms a binding funnel similar to the physics-based Rosetta Energy, suggesting that DFMDock can capture the underlying energy landscape.
MetaLab Platform Enables Comprehensive DDA and DIA Metaproteomics Analysis
Authors: Cheng Kai , Ning Zhibin , Zhang Xu , Duan Haonan , Mayne Janice , Figeys Daniel 
Published: September 2024

AbstractMetaproteomics studies the collective protein composition of complex microbial communities, providing insights into microbial roles in various environments. Despite its importance, metaproteomic data analysis is challenging due to the data’s large and heterogeneous nature. While Data-Independent Acquisition (DIA) mode enhances proteomics sensitivity, it traditionally requires Data-Dependent Acquisition (DDA) results to build the library for peptide identification.This paper introduces an updated version of MetaLab, a software solution that streamlines metaproteomic analysis by supporting both DDA and DIA modes across various mass spectrometry (MS) platforms, including Orbitrap and timsTOF. MetaLab’s key feature is its ability to perform DIA analysis without DDA results, allowing more experimental flexibility. It incorporates a deep learning strategy to train a neural network model, enhancing the accuracy and coverage of DIA results.Evaluations using diverse datasets demonstrate MetaLab’s robust performance in accuracy and sensitivity. Benchmarks from large-scale human gut microbiome studies show that MetaLab increases peptide identification by 2.7 times compared to conventional methods. MetaLab is a versatile tool that facilitates comprehensive and flexible metaproteomic data analysis, aiding researchers in exploring microbial communities’ functionality and dynamics.
The usual and unusual functions of thioredoxins in the metabolism and stress-response of sulfate-reducing bacteria
Authors: Majumder Erica L.-W. , Hou Liyuan , Whittle Fawn B. , Fitriasari Sharien , Trotter Valentine V. , Butland Gareth P. , Petzold Chris , Wall Judy D. 
Published: September 2024

AbstractThioredoxins are small, universal, disulfide isomerase proteins with required functions in oxidative stress response and RNA synthesis, among others. However, little is known about how anaerobic organisms maintain their intracellular redox balance or how thioredoxins may function differently under anaerobic metabolism. In this study, we investigated the roles of thioredoxins in sulfate-reducing microorganisms (SRMs). SRMs use sulfate as their primary electron acceptor in respiration to produce sulfide and are found in various environments including marine, freshwater sediments, guts and biofilms on ferrous metals where corrosion occurs. We found SRMs lack common redox maintenance molecules and macromolecules but have many and varied thioredoxins belonging to three types. Then, we probed their functions in the model SRM,Desulfovibrio vulgarisHildenborough (DvH), by anin vivodisulfide bond capture proteomics experiment in both non-stressed and oxidatively stressed conditions. Our results demonstrated that thioredoxin 1 (Trx1) was essential in DvH and selectively responded to oxidative stress. Our data supported its role in RNA synthesis and energy transduction since Trx1 interacted with DsrC and QmoB. Thioredoxin 3 (Trx3), an atypical thioredoxin, was observed to have roles in sulfur transfer and dissimilatory sulfur metabolism. Next, DvH thioredoxin system protein encoding genes were deleted and single deletion mutant strains were tested for growth phenotypes under a variety of different electron donors, acceptors and toxic metal stresses. It is found that dissimilatory sulfate reduction improves resistance of DvH to metal stress. It appeared the sulfide provided certain protection to DvH from silver and uranium stress.ImportanceWe put forth new functions for thioredoxins and a more robust understanding of sulfate reducing microorganisms physiology. Thioredoxin is of general interest because it has been widely studied for redox homeostasis or cancer therapies dealing with the excess of reactive oxygen species (ROS). Our results indicated that these proteins do have functions in stress response, even in microorganisms that generate large amounts of sulfide. We also identified interaction partners for an atypical thioredoxin, suggesting distinct roles from conserved thioredoxin. Mechanisms of metal stress response were found to be different than direct oxidative stress. Thioredoxin did not appear to be involved in uranium reduction electron transfer pathways, contradicting a hypothesis from the literature.
Structure-guided design and synthesis of C22- and C32-modified FK520 analogs with enhanced activity against human pathogenic fungi
Authors: Dome Patrick A. , Jeong Pyeonghwa , Nam Gibeom , Jang Hongjun , Rivera Angela , Averette Anna Floyd , Park Eunchong , Liao Tzu-Chieh , Ciofani Maria , Wu Jianli , Chi Jen-Tsan Ashley , Venters Ronald A. , Park Hyun-Ju , Steinbach William J. , Juvvadi Praveen R. , Heitman Joseph , Hong Jiyong 
Published: September 2024

AbstractInvasive fungal infections are a leading cause of death worldwide. Translating molecular insights into clinical benefits is challenging because fungal pathogens and their hosts share similar eukaryotic physiology. Consequently, current antifungal treatments have limited efficacy, may be poorly fungicidal in the host, can exhibit toxicity, and are increasingly compromised by emerging resistance. We have established that the phosphatase calcineurin (CaN) is required for invasive fungal disease and an attractive target for antifungal drug development. CaN is a druggable target, and there is vast clinical experience with the CaN inhibitors FK506 and cyclosporin A (CsA). However, while FK506 and its natural analog FK520 exhibit antifungal activity, they are also immunosuppressive in the host and thus not fungal-selective. We leverage our pathogenic fungal CaN-FK506-FKBP12 complex X-ray structures and biophysical data to support structure-based ligand design as well as structure–activity relationship analyses of broad-spectrum FK506/FK520 derivatives with potent antifungal activity and reduced immunosuppressive activity. Here we apply molecular docking studies to develop antifungal C22- or C32-modified FK520 derivatives with improved therapeutic index scores. Among them, the C32-modified FK520 derivative JH-FK-44 (7) demonstrates a significantly improved therapeutic index compared to JH-FK-08, our lead compound to date. NMR binding studies with C32-derivatives are consistent with our hypothesis that C32 modifications disrupt the hydrogen bonding network in the human complex while introducing favorable electrostatic and cation–π interactions with the fungal FKBP12 R86 residue. These findings further reinforce calcineurin inhibition as a promising strategy for antifungal therapy.SignificanceInvasive fungal infections cause significant mortality worldwide, and current antifungal treatments are often ineffective, toxic, or face growing resistance. This research identifies calcineurin (CaN), a critical protein for fungal survival, as a potential target for developing new antifungal drugs. Although existing CaN inhibitors such as FK506 (tacrolimus) and FK520 (ascomycin) possess antifungal properties, their immunosuppressive effects limit their clinical utility. By studying the structure of human and fungal FKBP12-FK506 or FK520 complexes with CaN, we have designed and synthesized modified FK520 derivatives with strong antifungal activity and reduced immunosuppressive effects. These new derivatives are expected to have significantly improved therapeutic profiles, offering hope for more effective and safer antifungal treatments.
Directed evolution of aminoacyl-tRNA synthetases throughin vivohypermutation
Authors: Furuhata Yuichi , Rix Gordon , Van Deventer James A. , Liu Chang C. 
Published: September 2024

AbstractGenetic code expansion (GCE) has become a critical tool in biology by enabling the site-specific incorporation of non-canonical amino acids (ncAAs) into proteins. Central to GCE is the development of orthogonal aminoacyl-tRNA synthetase (aaRS)/tRNA pairs wherein engineered aaRSs recognize chosen ncAAs and charge them onto tRNAs that decode blank codons (e.g., the amber stop codon). Many orthogonal aaRS/tRNA pairs covering a wide range of ncAAs have been generated by directed evolution, yet the evolution of new aaRS/tRNA pairs by standard strategies remains a labor-intensive process that often produces aaRS/tRNA pairs with suboptimal ncAA incorporation efficiencies. In this study, we present a strategy for evolving aaRSs that leverages OrthoRep to drive their continuous hypermutation in yeast. We demonstrate our strategy in 8 independent aaRS evolution campaigns starting from 4 different aaRS/tRNA parents targeting 7 distinct ncAAs. We observed the rapid evolution of multiple novel aaRSs capable of incorporating an overall range of 13 ncAAs tested into proteins in response to the amber codon. Some evolved systems reached efficiencies for amber codon-specified ncAA-dependent translation comparable to translation with natural amino acids specified by sense codons in yeast. Additionally, we discovered a surprising aaRS that evolved to self-regulate its own expression for greater dependency on ncAAs for translation. These findings demonstrate the potential of OrthoRep-driven aaRS evolution platforms in supporting the continued growth of GCE technologies.
Building molecular model series from heterogeneous CryoEM structures using Gaussian mixture models and deep neural networks
Authors: Chen Muyuan 
Published: September 2024

AbstractCryogenic electron microscopy (CryoEM) produces structures of macromolecules at near-atomic resolution. However, building molecular models with good stereochemical geometry from those structures can be challenging and time-consuming, especially when many structures are obtained from datasets with conformational heterogeneity. Here we present a model refinement protocol that automatically generates series of molecular models from CryoEM datasets, which describe the dynamics of the macromolecular system and have near-perfect geometry scores.
The claustrum enhances neural variability by modulating the responsiveness of the prefrontal cortex
Authors: Atilgan Huriye , Lazarte Ivan P. , Packer Adam M. 
Published: September 2024

AbstractThe claustrum is recognized for its significant impact on various cognitive functions and its extensive connections with other brain regions, yet its functional role remains to be fully understood. Here, we utilized an optogenetic approach to investigate the claustrum’s influence on neuronal activity within the dorsal prefrontal cortex (dPFC) of mice. We conducted two-photon calcium imaging to assess dPFC cell responses during exposure to visual stimuli and widefield photostimulation of claustrum axons embedded in the dPFC. We identified three distinct subpopulations of neurons — sensory responsive, opto responsive, and opto-boosted cells — each exhibiting unique response dynamics to combined visual and optogenetic stimuli. Our findings reveal that stimulation of claustrum axons can normalize neuronal responsiveness, while enhancing neural variability, and significantly increasing network homogeneity. Training in a Pavlovian task showed that while enhanced variability with claustrum axon stimulation in neural responses persists, training does not further increase this variability but instead leads to greater network homogeneity. Additionally, we also performed claustrum axon silencing experiments that revealed that the claustrum may operate bidirectionally to maintain enhanced variability and homogeneity in the prefrontal cortex. These results highlight the crucial role of the claustrum in dynamically modulating dPFC activity, impacting both neuronal variability and network synchronization.
Sealing and anti-seepage polyurea coating design method based on nonlinear FEM simulation
Authors: Li Bingqi , Zhang Jilei , Liu Xiaonan , Meng Tianyi 
Published: September 2024

Purpose Structural design theory and method for the polyurea coating system have rarely been developed. The normally used experience-based design method may lead to unsafe, unreasonable and uneconomic results. The purpose of this paper is to investigate the deformation and failure behaviour of the polyurea coating so as to propose a rational design method.Design/methodology/approach In this study, the fundamental theories concerning the nonlinear analysis of polyurea coating were discussed. Nonlinear Finite Element Method (FEM) models were built to investigate the mechanical behaviour, peeling behaviour and failure mode of the polyurea coating under various conditions, such as surface fracturing, surface hydraulic pressure and reverse hydraulic peeling.Findings The main conclusions are as follows. The peeled coating at the crack location exhibits a tensile-bending stress state. Coating material damage may occur at the stress concentration point. The maximum stress increases with the increase in the hydraulic pressure and cohesive strength. The peeling length of the coating decreases with the increase in cohesive strength and increases with the increase in fracture width. The reverse hydraulic pressure-induced blister edge stress concentration is the main trigger of the polyurea coating blistering damage. The blistering height decreases with increasing coating thickness and increases with increasing blistering radius and hydraulic load. The maximum stress increases with increasing blistering radius and hydraulic load. Finally, the frame of design and simple design programme were proposed.Originality/value Currently, a design method for polyurea anti-seepage coating can hardly be found. The reason is that the anti-seepage coating has only been recognized as a water-proofing layer, the mechanical behaviour of which has been ignored. This study focused on the mechanical behaviour of the anti-seepage coating and investigated the deformation and failure behaviour of the coating structure under various loading conditions through nonlinear FEM analysis. These research results offer a better understanding concerning the mechanical behaviour and design method of the polyurea anti-seepage coating.
Talent management in the hospitality and tourism industry: the role of societal and organisational culture
Authors: Kravariti Foteini , Jooss Stefan , Tom Dieck M. Claudia , Fountoulaki Paraskevi , Hossain Farhad 
Published: September 2024

Purpose
The purpose of this paper is to examine the role of societal and organisational culture on talent management (TM) within the Greek hospitality and tourism (H&T) industry. Specifically, this study tests societal culture’s effect on TM approaches and the mediating role of organisational culture.

Design/methodology/approach
In this quantitative study, the questionnaire sample included employees of all hierarchical levels from three hotels located in northern, central and southern Greece (n = 188). Data analyses were carried out by using the PROCESS Version 4 macro in SPSS.

Findings
The results show that neither societal nor organisational culture are decisive factors in impacting the perceived TM approach. This might be due to the organisations imitating other firms without pre-establishment of societal and organisational fit.

Practical implications
This study emphasises TM’s alignment with both societal and organisational culture. Given the context-specific nature of TM, achieving culture fit can enhance talent acquisition, retention and engagement, ultimately leading to improved talent and overall organisational performance.

Originality/value
This study integrates more centrally a cultural lens into the TM discourse. It provides empirical evidence of TM approaches in the Greek H&T industry, drawing on a multi-stakeholder sample including managers and talents.