bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain White Matter Microstructure are not associated with Blood Markers of the GSH Redox cycle in Schizophrenia
Authors: Pavan Tommaso , Steullet Pascal , Alemán-Gómez Yasser , Jenni Raoul , Schilliger Zoé , Cleusix Martine , Alameda Luis , Do Kim Q. , Conus Philippe , Hagmann Patric , Dwir Daniella , Klauser Paul , Jelescu Ileana
Published: January 2025

In groups of patients suffering from schizophrenia (SZ), redox dysregulation was reported in both peripheral fluids and brain. It has been hypothesized that such dysregulation, including alterations of the glutathione (GSH) cycle could participate in the brain white matter (WM) abnormalities in SZ due to the oligodendrocytes’ susceptibility to oxidative stress (OxS).

In this study we aim to assess the differences between 82 schizophrenia patients (PT) and 86 healthy controls (HC) in GSH-redox peripheral blood markers: GSH peroxidase (GPx), reductase (GR) enzymatic activities and their ratio (GPx/GR-ratio), evaluating the hypotheses that alterations in the homeostasis of the systemic GSH cycle may be associated with pathological mechanisms in the brain WM in PT. To do so, we employ the advanced diffusion MRI methods: Diffusion Kurtosis Imaging (DKI) and White Matter Tract Integrity-Watson (WMTI-W), which provide excellent sensitivity to demyelination and neuroinflammation.

We show that GPx levels are higher (p=0.00071) in female participants (HC and PT combined) and decrease with aging (p=0.026). We find differences between PT and HC in the association of GR and mean kurtosis (MK, p<0.0001). Namely, lower MK was associated with higher blood GR activity in HC, but not in PT, suggesting that high GR activity (a hallmark of reductive stress) in HC was linked to changes in myelin integrity. However, GSH-redox peripheral blood markers did not explain the WM anomalies detected in PT, or the design of the present study could not detect subtle phenomenon, if present.
Combining mpox vaccination and behavioural changes for mpox control among men who have sex with men: a mathematical modelling study
Authors: Xiridou Maria , van Wees Daphne Amanda , Adam Philippe , Miura Fuminari , Op de Coul Eline , Reitsema Maarten , de Wit John , van Benthem Birgit , Wallinga Jacco
Published: January 2025

Background

The 2022 outbreak of mpox subclade IIb in the Netherlands affected primarily men who have sex with men (MSM). Despite the sharp decline in cases, there are concerns about future mpox outbreaks. We investigated the impact of mpox introductions, accounting for vaccination, behavioural changes, and introductions of subclades with different characteristics.

Methods

We developed a compartmental model for mpox among MSM. We accounted for three risk levels for mpox, based on sexual activity, and allowed individuals to change risk level. We examined several scenarios with mpox introductions.

Results

In January 2024, 54% of MSM at high risk for mpox had immunity; this declined to 39% a year later, due to changes in risk levels. Mpox introductions in May 2025 resulted in small outbreaks, but the numbers of cases were 34% or 48% lower with vaccination carried out in August-October 2024 or February-April 2025, respectively, compared to the situation without vaccination in 2024-2025. With earlier initiation or greater magnitude of behavioural adaptations, the number of mpox cases was 17-51% smaller. Introduction of a subclade with 10% higher transmission probability than subclade IIb resulted in 77% more cases.

Conclusions

Due to changing levels of mpox risk, the fraction immune in the high-risk group will decline, leading to a greater possibilities for future mpox outbreaks. The number of cases can be reduced with preventive vaccination and behavioural adaptations. Recurring vaccination campaigns should prioritise individuals most at risk, ensuring those entering high-risk groups are reached. Campaigns promoting timely behavioural changes remain crucial.
Strategic Modulation of Polarity and Viscosity Sensitivity of Bimane Molecular Rotor-Based Fluorophores for Imaging α-Synuclein
Authors: Venkatesh Yarra , Narayan Karthik B. , Baumgart Tobias , Petersson E. James
Published: January 2025

Molecular rotor-based fluorophores (RBFs) that are target-selective and sensitive to both polarity and viscosity are valuable for diverse biological applications. Here, we have designed next-generation RBFs based on the underexplored bimane fluorophore through either changing in aryl substitution or varying π-linkages between the rotatable electron donors and acceptors to produce red-shifted fluorescence emissions with large Stokes shifts. RBFs exhibit a twisted intramolecular charge transfer mechanism that enables control of polarity and viscosity sensitivity, as well as target selectivity. These features enable their application in: (1) turn-on fluorescent detection of α-synuclein (αS) fibrils, a hallmark of Parkinson’s disease (PD), including amplified fibrils from patient samples; (2) monitoring early misfolding and oligomer formation during αS aggregation; and (3) selective imaging of αS condensates formed by liquid-liquid phase separation (LLPS). In all three cases, we show that our probes have high levels of selectivity for αS versus other aggregating proteins. These properties enable one to study the interplay of αS and tau in amyloid aggregation and the mechanisms underlying neurodegenerative disorders.
Noise-induced hearing loss enhances Ca2+-dependent spontaneous bursting activity in lateral cochlear efferents
Authors: Hong Hui , Trussell Laurence O
Published: January 2025

Exposure to loud and/or prolonged noise damages cochlear hair cells and triggers downstream changes in synaptic and electrical activity in multiple brain regions, resulting in hearing loss and altered speech comprehension. It remains unclear however whether or not noise exposure also compromises the cochlear efferent system, a feedback pathway in the brain that fine-tunes hearing sensitivity in the cochlea. We examined the effects of noise-induced hearing loss on the spontaneous action potential (AP) firing pattern in mouse lateral olivocochlear (LOC) neurons. This spontaneous firing exhibits a characteristic burst pattern dependent on Ca2+channels, and we therefore also examined the effects of noise-induced hearing loss on the function of these and other ion channels. The burst pattern was sustained by an interaction between inactivating Ca2+currents contributed largely by L-type channels, and steady outward currents mediated by Ba2+-sensitive inwardly-rectifying and two-pore domain K+channels. One week following exposure to loud broadband noise, hearing thresholds were significantly elevated, and the duration of AP bursts was increased, likely as a result of an enhanced Ca2+current. Additional effects of noise-induced hearing loss included alteration of Ca2+-dependent inactivation of Ca2+currents and a small elevation of outward K+currents. We propose that noise-induced hearing loss enhances efferent activity and may thus amplify the release of neurotransmitters and neuromodulators (i.e., neuropeptides), potentially altering sensory coding within the damaged cochlea.

Significance Statement

Although the effects of noise-induced hearing loss on the auditory afferent system have been extensively studied, little is known about its impact on the auditory efferent system, which modulates hearing sensitivity via feedback from the brain. Additionally, while Ca2+channels are related to numerous neurological diseases, their involvement in auditory disorders is underexplored. This study bridges these gaps by examining Ca2+channel-driven spontaneous burst firing in lateral olivocochlear (LOC) neurons, the most numerous auditory efferent neurons. Noise-induced hearing loss differentially affects Ca2+channel subtypes by increasing high-voltage activated currents that further prolong burst firing and suggesting altered intracellular Ca2+signaling. These significant changes in LOC firing behavior may profoundly impact their downstream targets in the cochlea.
Chest Wall Restriction Device for Modeling Respiratory Challenges and Dysfunction
Authors: Rodrigues Victoria Ribeiro , Mejia Lizuannette , Zucchi Rafael G. , Davenport Paul W. , Napoli Nicholas J.
Published: January 2025

Breathing relies on unrestricted movement of the chest wall to maintain O2 and CO2 balance. Understanding the effects of chest and abdominal restrictions on respiratory function is critical for studying conditions such as respiratory diseases, extreme environments, and load-induced impairments. However, existing methods to simulate these restrictions are limited, lacking the ability to provide both static and dynamic conditions or precise load control. To address these gaps, we developed a novel chest wall and abdomen restriction device capable of independently applying and measuring static and dynamic loads with adjustable and reproducible force levels. Separate bands for the chest and abdomen enable targeted restrictions, with constant force springs providing resistance during dynamic conditions and immobilization during static conditions. Integrated sensors quantify applied loads and respiratory mechanics. To validate the device, healthy participants underwent pulmonary function testing under baseline, static, and dynamic restriction conditions. Significant reductions in forced expiratory volume (FEV1) and forced vital capacity (FVC) were observed under restrictions compared to baseline. Other respiratory metrics also differed significantly, highlighting distinct effects of static and dynamic restrictions. Pressure variability tests confirmed reproducibility and adjustability of loads, while displacement data from linear variable differential transducers (LVDTs) validated the device’s ability to distinguish static and dynamic effects. This device addresses prior limitations by enabling precise, reproducible loading and independent control of chest and abdominal restrictions, supporting research into respiratory diseases, extreme environments, and respiratory mechanics. Our results demonstrate its potential to advance respiratory function research and expand clinical and experimental applications.
VTE incidence shortens survival in IDH-WT glioblastoma
Authors: Sloan Anthony R. , Gordillo Alan J. , Kennemer Austin , Khorana Alok A. , Horbinski Craig , Kaelber David C. , Cameron Scott J. , Lathia Justin D.
Published: January 2025

Background

Venous thromboembolisms (VTE’s) are the second leading cause of death in cancer patients. While previous analyses have demonstrated VTE rates are greater in GBM patients using smaller patient cohorts in high-grade glioma, since the release of the update 5thedition of the World Health Organization (WHO) classification a systematic analysis in a large-scale cohort of patients with IDH-wildtype GBM with clinical outcomes is lacking.

Methods

This study utilizes the online database, TriNetx, to build patient cohorts for outcomes analysis. TriNetX is a database comprised of over 50 healthcare organization patient information that is quarriable by CPT, ICD, RxNorm, and other proprietary codes. Patient cohort demographics were used for propensity score matching. Risk ratios, odds ratios, hazard ratios, and Kaplan Meier curves were utilized for primary outcomes including survival and time-to-event analyses.

Results

24% of patients with GBM experienced at least 1 VTE or PE after their diagnosis. Compared to a population of patients with no cancer history with an index event of an inpatient visit, patients with GBM were at 20.4 (12.23-34.17) and 5.96 (3.85-9.23) times higher risk of experiencing a VTE/PE at 1- and 5-year follow-up, respectively. Sex differences were not seen between VTE/PE rates and survival after VTE/PE at 1- and 5-year follow-up (p>0.05). Lastly, patients with GBM and a VTE/PE after diagnosis experienced worse survival at 1- and 5-year follow-up compared to those without a VTE/PE (p<0.0001 and p = 0.0014, respectively).

Conclusions

Patients with GBM experience increased risks of thrombotic events after diagnosis. These risks are not sex-dependent but do affect overall survival.
Patients Report Better Outcomes Following Reduction of Tibial Plateau Fractures: A Systematic Review
Authors: Kitchen David S. , Ricci Sebastian , Abrahams John M. , Downie Michael L. , Atkins Gerald J. , Solomon Lucian B. , Smitham Peter J.
Published: January 2025

Background

Tibial plateau fractures (TPF) are complex injuries involving the articular surface of the proximal tibia, commonly managed with open reduction and internal fixation (ORIF). The aim of this management is to restore joint alignment whilst respecting the soft tissue envelope. The relationship between radiological factors on patient-reported outcomes (PROMs) remains unclear. This systematic review aimed to determine the association between articular reduction and PROMs following TPF.

Methods

MEDLINE, Embase, Cochrane CENTRAL,ClinicalTrials.govand Google Scholar databases were searched for English language articles between January 2000 to 5 May 2023, with 3300 studies screened. Eligible studies reported radiological and clinical outcomes in adult TPF patients managed with ORIF, with a minimum follow-up of two years. Data extraction and quality assessment were conducted independently by two reviewers using the Risk of Bias Assessment tool for Non-Randomised Studies (RoBANS). Linear regression models assessed the effect of articular reduction on PROMs.

Results

A total of 30 studies met the inclusion criteria, comprising 1591 patients. Studies with >85% of cases achieving articular reduction within 2 mm reported significantly higher PROMs, particularly Hospital for Special Surgery (HSS) scores (p = 0.04). To analyse outcomes between studies that used different PROMs, a grouped analysis approach was utilised, which showed ‘excellent’ outcomes associated with cohorts in which higher rates of successful reduction were achieved when compared to ‘good’ outcomes (p = 0.04).

Conclusions

Achieving higher rates of articular reduction increases the likelihood of excellent patient-reported outcomes. Additionally, studies in which a larger proportion of the cohort achieved reduction reported significantly higher PROMs compared to those with fewer patients achieving anatomical reduction. This study also introduces a novel method to standardise the reporting of different PROMs in a meta-analysis, enabling comparison of heterogeneous data.
Longitudinal Measures of Cardiovascular Risk Factors Are Associated with Subfertility in the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Kim Catherine , Appiah Duke , Yin Zhe , Schreiner Pamela J. , Lewis Cora E. , McLaughlin Megan M. , Dula Adrienne N. , Siscovick David S. , Huddleston Heather
Published: January 2025

Introduction

Previous reports have noted associations between subfertility in women and increased risk of cardiovascular disease (CVD) events in later life. However, reports conflict regarding the associations between subfertility and CVD risk factors. Using data from a population-based cohort of Black and White women, we examined the association between longitudinal assessments of CVD risk factors and subfertility.

Methods

The Coronary Artery Risk Development in Young Adults (CARDIA) study is a prospective cohort of Black and White women who have undergone repeated assessment of CVD risk factors beginning at study baseline (1985-1986). Risk factors included cigarette smoking, body mass index (BMI), blood pressure, lipid levels, glucose, and C-reactive protein. At approximately 40 years of age, an ancillary study assessed histories of subfertility. We used generalized estimating equations with a logit link model to examine associations between subfertility (dependent variable) and repeated CVD risk factors (independent variables), with adjustment for age, race, center, and education level in 1107 women.

Results

Cigarette use and higher levels of BMI, glucose, and triglycerides and lower levels of high-density lipoprotein cholesterol (HDL) were associated with subfertility after adjustment for age, race, and education. In multivariable models which included all of these risk factors, cigarette use (odds ratio [OR] 1.004, 95% confidence interval [CI] 1.002, 1.006, p<0.0001) and HDL (OR 0.99, 95% CI 0.99, 0.995, p=0.046) were still associated with subfertility, but associations with BMI, glucose, and triglycerides were no longer significant.

Conclusions

Women with subfertility histories have adverse CVD risk factors across the reproductive lifespan. Cigarette use is a strong risk factor for infertility.
A New Interpretation for Oxygen Atom-Transfer Reactions for the Berg-Holm Oxo-Molybdenum Enzyme Model: Evidence for a Highly Active Oxygen Atom Transfer Acceptor
Authors: Berg Jeremy M.
Published: January 2025

In 1984, a synthetic model system for certain molybdenum oxotransferase enzymes was reported. These reports claimed that an oxygen atom could be extracted from a designed dioxomolybdenum(VI) complex to produce a monoxomolybdenum(IV) complex without the formation of an oxo-bridged molybdenum(V) binuclear species. The reduced product was shown to accept oxygen atoms from substrates such as dimethylsulfoxide with substrate saturation kinetics. Fifteen years later, it was demonstrated that the reduced product was, in fact, the oxo-bridged molybdenum(V) binuclear species. Here, it is shown that the kinetic data can be reinterpreted in terms of rate-limiting disproportionation of the oxo-bridged molybdenum(V) binuclear species to form a highly reactive monoxomolybdenum(IV) complex. The second order rate constant for oxygen atom transfer from dimethyl sulfoxide to this complex is more than 100,000 times higher than those reported for other monoxomolybdenum(IV) complexes. The five-coordinate molybdenum sites in the dioxomolybdenum(VI) and presumed monoxomolybdenum(IV) complexes are quite similar to those observed for eukaryotic nitrate reductase enzymes and this model system shows relatively rapid reduction of nitrate through a similar mechanistic scheme.
Trace metals availability controls terminal electron acceptor utilization inEscherichia coli
Authors: Ricciardelli Annarita , de Pins Benoit , Brusca Jacopo , Correggia Monica , Di Iorio Luciano , Cascone Martina , Giardina Marco , Castaldi Stefany , Isticato Rachele , Iacono Roberta , Moracci Marco , Nappi Nunzia , Pollio Antonino , Vetriani Costantino , Leone Serena , Cordone Angelina , Giovannelli Donato
Published: January 2025

Trace metals play an essential role in the metabolism of all living organisms and many metal-containing enzymes contribute to key physiological and ecological processes such as aerobic and anaerobic respiration, photosynthesis, carbon and nitrogen fixation. Despite this, trace metals’ potential to control microbial functional diversity and metabolic shifts is unknown. Here we demonstrate that the availability of trace metals controls electron acceptors utilization inEscherichia coli. Physiological and proteomic data show that trace metals depleted cultures have significantly reduced growth, start fermentation and increase energy expenditure for metal homeostasis even when more energetically favourable electron acceptors are present. Overall these results suggest how evolutionary and competitive pressures arising from changes in biological trace metals availability in deep time have contributed to shaping evolution and competition.
Extracellular vesicles of a phytobeneficial bacterium trigger distinct systemic response in plant
Authors: Zannis-Peyrot Timothée , Degusseau Lucas , Dugas Pierre-Yves , Bastian Fabiola , Gaucher Matthieu , Gaillard Vincent , Comte Gilles , Wisniewski-Dye Florence , Kerzaon Isabelle , Lavire Céline , Vial Ludovic
Published: January 2025

Bacterial extracellular vesicles (EVs) are lipidic shuttles that play roles in virulence, inter-species competition, and in the induction of the host immune response. While they have primarily been investigated in animal-bacteria interactions, knowledge regarding phytobacterial EVs remains limited. Recent findings revealed that various biotic factors like hydroxycinnamic acids can regulate EVs production. Hydroxycinnamic acids, such as ferulic acid, are lignin components abundantly released in the plant environment, where they impact the ecology of numerous phytobacteria.Azospirillumsp. B510, a phytobeneficial bacterium, induces the accumulation of hydroxycinnamic acid derivatives in the plant and can metabolize them as carbon sources. We hypothesized that the presence of ferulic acid in the environment ofAzospirillumsp. B510 would influence its EVs production in terms of size, quantity, and cargo. Conversely, we also proposed that EVs from this phytobacterium would influence plant metabolites and defense gene expression. Our results show both that ferulic acid (mimicking the plant environment) influences the content of EVs released byAzospirillumsp. B510 and that bacterial EVs also impact plant physiology at a systemic level according to their cargoes. This research provides the first evidence of a global effect of bacterial EVs on the plant and highlights the dynamics of plant-bacteria interactions mediated by EVs.
The spinal premotor network driving scratching flexor and extensor alternation
Authors: Yao Mingchen , Nagamori Akira , Azim Eiman , Sharpee Tatyana , Goulding Martyn , Golomb David , Gatto Graziana
Published: January 2025

Rhythmic motor behaviors are generated by neural networks termed central pattern generators (CPGs). Although locomotor CPGs have been extensively characterized, it remains unknown how the neuronal populations composing them interact to generate adaptive rhythms. We explored the non-linear cooperation dynamics among the three main populations of ipsilaterally projecting spinal CPG neurons – V1, V2a, V2b neurons – in scratch reflex rhythmogenesis. Ablation of all three neuronal subtypes reduced the oscillation frequency. Activation of excitatory V2a neurons enhanced the oscillation frequency, while activating inhibitory V1 neurons caused atonia. These findings required the development of a novel neuromechanical model that consists of flexor and extensor modules coupled via inhibition, in which rhythm in each module is generated by self-bursting excitatory populations and accelerated by intra-module inhibition. Inter-module inhibition coordinates the phases of flexor and extensor activity and slows the oscillations, while facilitation mechanisms in excitatory neurons explain the V2a activation-driven increase in frequency.
Resting State connectivity patterns associated with trait anxiety in adolescence
Authors: Baggio Teresa , Grecucci Alessandro , Crivello Fabrice , Joliot Marc , Tzourio Christophe
Published: January 2025

Anxiety symptoms can vary across different life stages, with a higher frequency during adolescence and early adulthood, increasing the risk of developing future anxiety disorders. To date, neuroscientific research on anxiety has primarily focused on adulthood, thus limiting our understanding of how anxiety may characterize earlier stages of life, and employing mostly univariate approaches, thus discounting large-scale alterations of the brain. One intriguing hypothesis is that adolescents with trait anxiety may display similar abnormalities shown by adults in brain regions ascribed to the Default Mode Network (DMN) associated with self-referential thinking, awareness, and rumination-related processes. The present study aims to expand our previous knowledge on this topic using a large sample of young individuals to uncover the resting-state connectivity patterns associated with trait anxiety in a network approach. To test our hypotheses, we analyzed the rs-fMRI images of 1263 adolescents (mean age 20.55 years) as well as their scores on anxiety trait. A significant association between trait anxiety and resting-state functional connectivity in two networks was found, with some regions overlapping with the Default Mode Network. The first network included regions such as the cingulate gyrus and the middle temporal gyri known to be involved in self-referential processing and emotional perception and control, both altered in anxiety disorders. The second network included the precuneus, possibly related to rumination that characterizes anxiety. Of note, the higher the trait anxiety, the lower the connectivity within both networks, suggesting abnormal self-referential processing, awareness, and emotion regulation abilities in adolescents with high anxiety trait. These findings provided a better understanding of the association between trait anxiety and brain rs-functional connectivity, and may pave the way for the development of potential biomarkers in adolescents with anxiety.
Functional Equivalence of the Proneural GenesNeurog1andNeurog2in the Developing Dorsal Root Ganglia Highlights the Importance of Timing of Neurogenesis in Biasing Somatosensory Precursor Fates
Authors: Desiderio Simon , Cabochette Pauline , Venteo Stephanie , Tejedor Gautier , Djouad Farida , Carroll Patrick , Ango Fabrice , Pattyn Alexandre
Published: January 2025

Distinct subfamilies of proneural bHLH transcription factors (TFs) control neurogenesis and influence neuronal fate specification throughout the developing nervous system. While members of different subfamilies generally display divergent expression and functions, those within the same subfamily are often co-expressed, raising questions about their respective roles. Here, we assess the functional equivalence of the two paralogous proneural TFs Neurog1 and Neurog2, focusing on neurons of the dorsal root ganglia (DRG) which underlie our ability to process somatosensory information. During development, distinct classes of DRG neurons -classified as mechano/proprioceptors or thermo/nociceptors-are generated during two successive neurogenic phases, which are respectively controlled by Neurog2 and Neurog1, in line with their dynamic and complementary spatiotemporal expression patterns. Therefore, in this system, each TF appears to play unique roles in regulating neurogenesis and specifying distinct neuronal identities. Yet, using a gene replacement strategyin vivo, we show that, despite subtle divergences masked by dose-compensation effects, Neurog1 and Neurog2 are essentially functionally interchangeable in all aspects of DRG development, indicating that their apparent functional discrepancies primarily stem from divergent evolution of their gene regulatory regions, rather than of their respective biochemical properties. Notably, we definitively establish that neither TF directly specifies specific somatosensory neuron identities. This result, combined with : (i) a new series of birth-dating experiments supporting that most mechano/proprioceptive and thermo/nociceptive subtypes are predominantly born during successive time-windows; and (ii) analyses of complementary transgenic mouse models in which opposite temporal shifts of neurogenesis -either delayed onset or premature arrest-have predictable opposite impacts on their DRG content, highlight that the fate choice of somatosensory precursors toward the mechano/proprioceptive or thermo/nociceptive lineages critically depends on the timing of their birth.
Temporal recurrence as a general mechanism to explain neural responses in the auditory system
Authors: Rançon Ulysse , Masquelier Timothée , Cottereau Benoit R
Published: January 2025

Computational models of neural processing in the auditory cortex usually ignore that neurons have an internal memory: they characterize their responses from simple convolutions with a finite temporal window of arbitrary duration. To circumvent this limitation, we propose here a new, simple and fully recurrent neural network (RNN) architecture incorporating cutting-edge computational blocks from the deep learning community and constituting the first attempt to model auditory responses with deep RNNs. We evaluated the ability of this approach to fit neural responses from 8 publicly available datasets, spanning 3 animal species and 6 auditory brain areas, representing the largest compilation of this kind. Our recurrent models significantly outperform previous methods and a new Transformer-based architecture of our design on this task, suggesting that temporal recurrence is the key to explain auditory responses. Finally, we developed a novel interpretation technique to reverse-engineer any pretrained model, regardless of their stateful or stateless nature. Largely inspired by works from explainable artificial intelligence (xAI), our method suggests that auditory neurons have much longer memory (several seconds) than indicated by current STRF techniques. Together, these results highly motivate the use of deep RNNs within computational models of sensory neurons, as protean building blocks capable of assuming any function.
Structure of mycobacterial NDH-2 bound to a 2-mercapto-quinazolinone inhibitor
Authors: Liang Yingke , Bueler Stephanie A. , Cook Gregory M. , Rubinstein John L.
Published: January 2025

The mycobacterial type II NADH dehydrogenase (NDH-2) is a promising drug target because of its central role in energy metabolism inMycobacterium tuberculosisand other pathogens, and because it lacks a known mammalian homologue. However, the absence of structural information on how the enzyme binds inhibitors has made optimization of lead compounds challenging. We used electron cryomicroscopy (cryo-EM) to determine the structure of NDH-2 fromMycobacterium smegmatis, a fast-growing non-pathogenic model for respiration inM. tuberculosis, both alone and in complex with a 2-mercapto-quinazolinone inhibitor. The structure shows that active mycobacterial NDH-2 is dimeric, with the dimerization interface stabilized by an extended C-terminal α helix not found in NDH-2 from other bacterial genera.

The arrangement of monomers in the dimer differs from the arrangement described for other prokaryotic NDH-2 dimers, instead resembling dimers formed by NDH-2 in eukaryotes. Density for the 2-mercapto-quinazolinone in the menaquinone-binding site shows that the inhibitor blocks menaquinone reduction through direct interaction with the flavin adenine dinucleotide cofactor. These results reveal structural elements of NDH-2 that could be used to design specific inhibitors of the mycobacterial enzyme.
Pseudopaline-mediated zinc uptake byPseudomonas aeruginosadetermines specific clinically relevant phenotypes and infection outcome
Authors: Bosc L , Sécher T , Ball G , Le Pennec D , Tribout M , Ba M , Bai Y , Ouerdane L , Arnoux P , Denis Y , Lei X , Bordi C , Heuzé-Vourc’h N , Häussler S , Gomez NO , Voulhoux R
Published: January 2025

AUTHOR SUMMARY

The host-pathogen interface is a biological niche in which two entities competes for essential resources. The host’s nutritional immunity restrict access to metals, while a successful pathogen overcomes these restrictions using dedicated uptake pathways. Pseudopaline is a high-affinity metallophore allowingPseudomonas aeruginosato acquire zinc in chelated environments. We demonstrate that this pathway is the last-resort solution to acquire zinc for this dreadful pathogen. The capacity to provide this metal to zinc-metalloproteins drives clinically relevant phenotypes, such as the capacity to form a mature and antibiotic-tolerant biofilm, or to affect the outcome of an infection. These results place pseudopaline as a potential drug target for blockingP. aeruginosapathogenic capacity and resensitizing established biofilm to classic antibiotic treatment.

Biological metals are essential trace elements which are required by metalloproteins, involved in virtually every cellular, structural and catalytic function of the bacterial cell. Bacterial pathogenesis involves a tug-of-war between the host nutritional immunity, sequestering essential metals and the invading pathogens that deploy high-metal affinity uptake strategies in order to overcome these defence mechanisms. Metallophores are high-affinity, low-molecular mass metal chelators produced and secreted by bacteria to access chelated metals from the environment. Pseudopaline is a metallophore produced and secreted byPseudomonas aeruginosato acquire zinc when the bioavailability of this metal is severely restricted, as in the presence of a strong metal chelator such as EDTA, or during infections when the nutritional immunity of the host is active, in mammals through the production of the zing binding protein calprotectin. We show that under the conditions of metal deprivation, a pseudopaline-deficientP. aeruginosastrain exhibit a severe intracellular zinc deficiency, establishing that the pseudopaline pathway is the last-resort and unique pathway for the bacteria to acquire zinc under these restricted growth conditions. The present study explores the pleiotropic role of pseudopaline-mediated zinc acquisition on several clinically relevant phenotypes and its capacity to drive infection outcomes, placing this machinery as a promising therapeutic target forP. aeruginosa’s infection, acting synergistically as a pathogenicity determinant as well as an adaptative trait allowing the establishment of a mature and antibiotic resistance biofilm necessary for recalcitrant chronic infections.
Ensemble priming via competitive inhibition: local mechanisms of sensory context storage and deviance detection in the neocortical column
Authors: Thorpe Ryan V. , Moore Christopher I. , Jones Stephanie R.
Published: January 2025

The process by which neocortical neurons and circuits amplify their response to an unexpected change in stimulus, often referred to as deviance detection (DD), has long been thought to be the product of specialized cell types and/or routing between mesoscopic brain areas. Here, we explore a different theory, whereby DD emerges from local network-level interactions within a neocortical column. We propose that deviance-driven neural dynamics can emerge through interactions between ensembles of neurons that have a fundamental inhibitory motif: competitive inhibition between reciprocally connected ensembles under modulation from feed-forward selective (dis)inhibition. Using this framework, we were able to simulate a variety of phenomena pertaining to the experimentally observed shifts in neural tuning across neurons, time, and stimulus history. Anchoring our approach in a variety of experimentally observed phenomena, we used computation modeling in two types of neural networks of vastly different levels of biophysical detail to test hypotheses on emergent dynamics and explore the robustness of underlying connectivity parameters. With a number of corollary predictions that can be tested in future in vivo studies, we show that ensemble priming via competitive inhibition under modulation from selective (dis)inhibition acts as a local mechanism for sensory context storage and that DD does not require specialized input from other brain areas—a novel theoretical paradigm that resolves previously confounding aspects of sensory encoding and predictive processing in the neocortex.
Starshipgiant transposons dominate plastic genomic regions in a fungal plant pathogen and drive virulence evolution
Authors: Sato Yukiyo , Bex Roos , van den Berg Grardy C. M. , Höfte Monica , Seidl Michael F. , Thomma Bart P.H.J.
Published: January 2025

Starshipsform a recently discovered superfamily of giant transposons in Pezizomycotina fungi, implicated in mediating horizontal transfer of diverse cargo genes between fungal genomes. Their elusive nature has long obscured their significance, and their impact on genome evolution remains poorly understood. Here, we reveal a surprising abundance and diversity ofStarshipsin the phytopathogenic fungusVerticillium dahliae. Remarkably,Starshipsdominate the plastic genomic compartments involved in host colonization, are enriched in virulence-associated genes, and exhibit genetic and epigenetic characteristics associated with adaptive genome evolution. We further uncover extensive horizontal transfer ofStarshipsbetweenVerticilliumspecies and, strikingly, from distantly relatedFusariumfungi. Finally, we demonstrate howStarshipactivity facilitated thede novoformation of a novel virulence gene. Our findings illuminate the profound influence ofStarshipdynamics on fungal genome evolution and the development of virulence.
Probing electron-photon entanglement using a quantum eraser
Authors: Henke Jan-Wilke , Jeng Hao , Ropers Claus
Published: January 2025

We propose a tangible experimental scheme for demonstrating quantum entanglement between swift electrons and light, relying on coherent cathodoluminescence for photon generation in a transmission electron microscope, and a quantum eraser setup for formation and verification of entanglement. The entanglement of free electrons with light is key to developing free-electron quantum optics and its potential applications such as quantum sensing, novel photonic and electron state generation, and entanglement between free electrons.

Published by the American Physical Society
2025
Distinct creep regimes of methane hydrates predicted by a monatomic water model
Authors: Sveinsson Henrik Andersen , Cao Pinqiang
Published: January 2025

The power-law creep properties of methane hydrates were measured experimentally two decades ago, but their microscopic explanation is still missing. Here we show, using molecular dynamics simulations spanning almost 2 orders of magnitude of stresses and 3 orders of magnitude of strain rates, that such power-law creep emerges in molecular dynamics simulations of polycrystalline methane hydrates using a monatomic water model, suggesting that only simplified molecular interactions and the concept of a hydrate polycrystal are needed for such power-law creep behavior to emerge. Damage patterns post-creep suggest that hydrates are strong because damage only occurs on crystal surfaces.

Published by the American Physical Society
2025
Crystallographic analysis of the Escherichia coli tRNA seleno-modification enzyme in complex with tRNA
Authors: Usui Takuya , Ono Sayaka , Nakamura Akiyoshi , Kato Koji , Ose Toyoyuki , Yao Min
Published: January 2025

The bacterial enzyme tRNA 2-selenouridine synthase (SelU) catalyzes the conversion of 5-substituted 2-thiouridine (R5S2U) to 5-substituted 2-selenouridine (R5Se2U) at the wobble positions of several tRNAs. Seleno-modification potentially regulates translation efficiency in response to selenium availability. Notably, SelU uses the 2-geranylthiouridine (R5geS2U) intermediate for sulfur removal, and this geranylthiol (geS) is a unique leaving group among tRNA-maturation enzymes. However, the underlying sequence of the SelU reaction remains unclear. Here, a crystallographic study of the Escherichia coli SelU–tRNA complex is reported. Robust and well formed SelU–tRNA crystals were obtained after several optimizations, including co-expression with tRNA and additive screening. Diffraction data were collected at a resolution of 3.10 Å using a wavelength of 1.0000 Å. The crystals belonged to space group C2, and the phase was determined by molecular replacement using the AlphaFold2-predicted SelU structure as a search model. Electron-density mapping revealed the presence of two SelU–tRNA complexes in the asymmetric unit.
Symmetric 3-periodic polycatenanes: catenated rings, polyhedra and rods
Authors: O'Keeffe Michael , Treacy Michael M. J.
Published: January 2025

We report symmetric (vertex- and arc-transitive) embeddings of catenated rings, polyhedra and rods. Linked triangles form infinite families of structures, and we limit this report to only structures with each ring linked to three or six others. For linked squares, hexagons, tetrahedra, octahedra, cubes and rods, only a small number of symmetric structures were found, and all are reported.
Corrosion behavior of Cu-containing 3Ni steel in simulated marine environments with different NaCl concentrations
Authors: Ke Weipeng , Kang Yiyao , Dong Baojun , Liao Wei , Ji Xiaolong , He Jianchao , Leng Xuesong , Chen Hongsheng
Published: January 2025

Purpose

This study aims to investigate the corrosion behavior of Cu-containing 3Ni steel in simulated marine environments and to provide basic guidance for improving the corrosion resistance of marine high-strength steels.

Design/methodology/approach

The corrosion properties of Cu-containing 3Ni steel were evaluated in five different NaCl concentrations by alternating wet and dry cycling method. The corrosion behavior was investigated by electrochemical impedance spectroscopy, scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The mechanism of the influence of Cl ion concentrations on the corrosion behavior of Cu-containing 3Ni steel in marine environments was analyzed.

Findings

The results showed that the corrosion resistance of Cu-containing 3Ni steel decreased with NaCl concentration increasing. With the increase of NaCl concentration, the number of FeOOH particles decreased and their size increased, resulting in an increase in the porosity and a decrease in the density of corrosion products. High NaCl concentration could inhibit the formation of NiFe2O4 and disrupt the electronegativity of the inner film of corrosion products, which further weakened the enrichment of Ni and Cu, and enhanced the permeability of Cl ions.

Originality/value

The influence of NaCl concentrations on the corrosion behavior of Cu-containing 3Ni steel was systematically studied and the influence laws of corrosion behavior were obtained in this paper, providing basic data for the optimal design of Cu-containing 3Ni steels.
AI avatars and co-creation in the metaverse
Authors: Ramadan Zahy , Ramadan Jad
Published: January 2025

Purpose

While the fields of artificial intelligence (AI) and avatars are growing at a very fast pace, studies are still scarce. This study aims to fill the gap in the literature relating to the implications of highly realistic avatars as well as the consequences of AI-led co-creation on hospitality services in the Metaverse.

Design/methodology/approach

The authors adopted an exploratory qualitative methodology to study the role of AI avatars in the Metaverse within the hospitality context. The study involved interviews with both elite figures and consumers as primary data and also incorporated secondary data sourced from comments on a YouTube video related to avatars.

Findings

Based on data triangulation, the extracted themes dealt with four key areas: (1) avatars’ relational encounters in hospitality, (2) avatars’ realism, (3) self-representation and self-perception skewness and (4) AI co-creation. The findings show that while avatars’ realism would increase the authenticity of virtual social connections, engagement and monetization, the issue of a self-misrepresentation will diminish the effect of virtual encounters. That avatars will be AI led and will digitally cocreate reviews and recommendations further accentuates the findings.

Originality/value

This research advances the field by addressing the literature gap on AI-led avatar realism and co-creation in hospitality services within the Metaverse. It explores the nuanced ways that highly realistic avatars can enhance engagement and self-representation while simultaneously posing challenges related to authenticity and trust. The study provides a foundation for further exploration of AI’s transformative potential in virtual hospitality contexts.
The curvilinear and contingent effect of ethical climate on salesperson performance
Authors: Johnson Jeff S. , Friend Scott B.
Published: January 2025

Purpose

The purpose of this paper is to provide empirical understanding germane to ethical climate’s contingent, nonlinear relationship with salesperson performance. While research shows a positive relationship between a firm’s ethical climate and salesperson performance, current examinations of this effect have been limited to linear hypothesizing and testing. The job demands-resource model, however, suggests that the relationship between ethical climate and salesperson performance is nonlinear.

Design/methodology/approach

To test the theorized nonlinear and moderated nonlinear relationships, the authors use a sample of 485 business-to-business salespeople and structural equations path modeling.

Findings

Results reveal an increasing incremental threshold effect between ethical climate and salesperson performance. Findings further support postulations that conditions which increase (e.g. competitive intensity) or decrease (e.g. role autonomy) the extent to which the sales environment is challenging correspondingly increase or decrease the magnitude of the nonlinearity.

Research limitations/implications

Because the study required variance in environmental-level (e.g. competitive intensity) and organizational-level (e.g. role autonomy) moderators, data used to test the hypotheses came from a cross-sectional, self-reported survey.

Practical implications

The results produce the managerial insight that there are increasing returns to salesperson performance as the ethical climate increases. Insights from the analysis of moderating conditions further inform managers that in highly competitive industries they should be especially attuned to their ethical climate.

Originality/value

To the best of the authors’ knowledge, the findings are the first to advance insight into ethical climate’s curvilinear and contingent salesperson performance implications. Furthermore, this study advances moderated nonlinear relationships suggested by theory.
Understanding project cost contingency estimation: a holistic risk perspective
Authors: Zhang Liting , Li Yadi , Sun Ning , Ning Yan
Published: January 2025

Purpose

Cost contingency is widely employed to address project risks. This systematic literature review aims to develop a framework for understanding risks in project cost contingency estimation.

Design/methodology/approach

A systematic literature review of 859 abstracts and 67 full articles was conducted using a framework synthesis method.

Findings

The study establishes a six-element risk framework for project cost contingency estimation, encompassing event, consequence, uncertainty, probability, knowledge, and mitigation. Twelve risk dimensions in the project cost contingency estimation are further developed.

Originality/value

This study contributes to the project management literature by constructing a framework for understanding risks in project cost contingency estimation. This framework provides guidance for enhancing the accuracy of project cost contingency estimation.
Global value chains, trade facilitation and the use of environmental management practices in SMEs
Authors: Ranasinghe Udish Chalana , Ennis Sean Forrest , Monteiro Januario , Malagueño Ricardo
Published: January 2025

Purpose

This study investigates the relationship between small and medium-sized enterprises' (SMEs) participation in global value chains (GVCs) and the use of environmental management practices. The study examines the role of national governments in shaping this relationship, specifically exploring the role of trade facilitation. The emphasis lies on understanding the extent to which GVCs and governmental policy interaction relate to improved environmental management practices among SMEs.

Design/methodology/approach

The study builds on several publicly available data sources, including the World Bank’s Archival Enterprise Surveys and the Organisation for Economic Cooperation and Development Trade Facilitation Indicator. The sample includes 1,462 SMEs in 18 countries. To test our hypotheses, we use regression analysis employing bootstrapping techniques for rigorous testing of direct and indirect associations.

Findings

Results indicate that SMEs tend to use environmental management practices when entering GVCs but not after exiting. Moreover, the study suggests that a non-linear feature of trade facilitation plays an important role in mitigating the relationship between SMEs exit from GVCs and SMEs abandonment of environmental management practices.

Originality/value

The relationship between SMEs entering and exiting GVCs and environmental management practices is not well understood. It is still unclear whether the external pressures and governmental policies to stimulate trade contribute to improving the sustainability behaviour of SMEs. This study adds to the operations management literature by relating government policies with the use of environmental management practices, providing insights on the relationship between deglobalisation and SMEs sustainability activities.