bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated Atherogenicity in Long COVID: A Systematic Review and Meta-Analysis
Authors: Almulla Abbas F. , Thipakorn Yanin , Zhang Yingqian , Maes Michael 
Published: January 2025

AbstractBackgroundLong COVID (LC) is a complex, multi-organ syndrome that persists following recovery from the acute phase of coronavirus infection. Cardiovascular involvement is frequently reported in LC, often accompanied by a spectrum of related symptoms. Dysregulated lipid profiles and elevated atherogenic indices have been implicated in LC, yet no comprehensive systematic review and meta-analysis has specifically addressed these biomarkers.ObjectiveThis study aims to systematically evaluate atherogenic indices and lipid-related biomarkers in individuals with LC compared to healthy controls.MethodsA systematic search was conducted in databases including PubMed, Google Scholar, SCOPUS, and SciFinder from September to November 2024. Eligible studies reported lipid biomarker data for LC patients and controls, yielding 44 studies encompassing 8,114 participants (3,353 LC patients and 4,761 controls).ResultsLC patients exhibited significant elevations in Castelli Risk Indexes 1 (standardized mean difference, SMD = 0.199; 95% confidence intervals, CI: 0.087–0.312) and 2 (SMD = 0.202; 95% CI: 0.087–0.318). Atherogenic ratios, including triglyceride (TG)/high-density lipoprotein (HDL) (SMD = 0.294; 95% CI: 0.155–0.433), (TG + low-density lipoprotein, LDL + very low-density lipoprotein, VLDL)/(HDL + apolipoprotein, ApoA) (SMD = 0.264; 95% CI: 0.145–0.383), and ApoB/ApoA (SMD = 0.515; 95% CI: 0.233–0.796), were also significantly elevated. Additionally, LC patients demonstrated increased levels of LDL, total cholesterol, triglycerides, and ApoB, alongside reduced HDL and ApoA levels. Results were free from publication bias.ConclusionLC is associated with a pro-atherogenic lipid profile, marked by increased atherogenic components and decreased protective lipid biomarkers. These findings highlight a potential heightened risk for cardiovascular complications in LC patients, warranting further clinical and mechanistic investigations.
Sequence-dependent co-condensation of Lsr2 with DNA elucidates the mechanism of genome compaction inMycobacterium tuberculosis
Authors: Satheesh Thejas , Singh Rohit Kumar , Gaur Prakshi , Shahu Sneha , Ramakrishnan Saminathan , Srivastava Mansi , Neogi Shreyasi , Choubey Sandeep , Ganji Mahipal 
Published: January 2025

AbstractThe xenogeneic silencer protein Lsr2 fromMycobacterium tuberculosisplays a critical role in its survival and pathogenesis. Lsr2 is a nucleoid-associated protein that interacts with DNAin vivoand regulates many genes. Purified Lsr2 forms nucleoprotein filaments with DNA molecules leading to highly compacted DNA conformations. However, the physical mechanism underlying Lsr2-mediated DNA compaction, resulting in gene regulation, remains elusive. We employed a combination of biochemical assay, single-molecule imaging, and molecular dynamics simulations to investigate the governing principles of Lsr2-mediated DNA compaction. We show that, while Lsr2 alone undergoes phase separation, addition of DNA substantially lowers the required concentration for its phase separation. Strikingly, our single-molecule and simulation data establish that Lsr2 forms condensates with long stretches of AT-rich DNA, providing strong evidence for sequence-dependent co-condensation. This observation is contrary to the classical view of sequence-dependent binding of individual protein molecules to DNA, our findings rather suggest that protein-DNA co-condensates ‘sense’ the average binding energy landscape. We present a physical model for Lsr2-mediated DNA compaction and gene regulation, describing a novel mechanism for NAP-mediated genome organization in bacteria.
Navigating uncertainty: reward location variability induces reorganization of hippocampal spatial representations
Authors: Tessereau Charline , Xuan Feng , Mellor Jack R. , Dayan Peter , Dombeck Daniel 
Published: January 2025

AbstractNavigating uncertainty is crucial for survival, with the location and availability of reward varying in different and unsignalled ways. Hippocampal place cell populations over-represent salient locations in an animal’s environment, including those associated with rewards; however, how the spatial uncertainties impact the cognitive map is unclear. We report a virtual spatial navigation task designed to test the impact of different levels and types of uncertainty about reward on place cell populations. When the reward location changed on a trial-by-trial basis, inducing expected uncertainty, a greater proportion of place cells followed along, and the reward and the track end became anchors of a warped spatial metric. When the reward location then unexpectedly moved, the fraction of reward place cells that followed was greater when starting from a state of expected, compared to low, uncertainty. Overall, we show that different forms of potentially interacting uncertainty generate remapping in parallel, task-relevant, reference frames.
A mechanistic understanding of the effect ofStaphylococcus aureusVraS histidine kinase single point mutation on antibiotic resistance
Authors: Ali Liaqat , Karki Salima , Boorgula Gunavanthi D , Mekakda Amir , Cagle-White Brittnee , Bhattarai Shrijan , Beaudoin Robert , Blakeney Aryanna , Singh Sanjay , Srivastava Shashikant , Abdelaziz May H. 
Published: January 2025

AbstractBacterial genomic mutations inStaphylococcus aureus (S. aureus)have been detected in isolated resistant clinical strains, yet their mechanistic effect on the development of antimicrobial resistance remains unclear. The resistance-associated regulatory systems acquire adaptive mutations under stress conditions that may lead to a gain of function effect and contribute to the resistance phenotype. Here, we investigate the effect of a single-point mutation (T331I) in VraS histidine kinase, part of the VraSR two-component system inS. aureus.VraSR senses and responds to environmental stress signals by upregulating gene expression for cell wall synthesis. A combination of enzyme kinetics, microbiological, and transcriptomic analysis revealed the mechanistic effect of the mutation on VraS andS. aureus. Michaelis Menten’s kinetics show that the VraS mutation caused an increase in the autophosphorylation rate of VraS and enhanced its catalytic efficiency. The introduction of the mutation through recombineering coupled with CRISPR-Cas9 counterselection to the Newman strain wild-type (WT) genome doubled the minimum inhibitory concentration of three cell wall-targeting antibiotics. The mutation caused an enhancedS. aureusgrowth rate at sub-lethal doses of the antibiotics, confirming the causative effect of mutation on bacterial persistence. Transcriptomic analysis showed a genome-wide alteration in gene expression levels and protein-protein interaction network of the mutant compared to the WT strain after exposure to vancomycin. The results suggest thatvraSmutation causes several mechanistic changes at the protein and cellular levels that favor bacterial survival under antibiotic stress and cause the mutation-harboring strains to become the dominant population during infection.ImportanceRising antimicrobial resistance (AMR) is a global health problem. Mutations in the two- component system have been linked to drug- resistance inStaphylococcus aureus, yet the exact mechanism through which these mutations work is understudied. We investigated the T331I mutation in thevraSgene linked to sensing and responding to cell wall stress. The mutation caused changes at the protein level by increasing the catalytic efficiency of VraS kinase activity. Introducing the mutation to the genome of anS. aureusstrain resulted in changes in the phenotypic antibiotic susceptibility, growth kinetics, and genome-wide transcriptomic alterations. By a combination of enzyme kinetics, microbiological, and transcriptomic approaches, we highlight how small genetic changes can significantly impact bacterial physiology and survival under antibiotic stress. Understanding the mechanistic basis of antibiotic resistance is crucial to guide the development of novel therapeutic agents to combat AMR.
Unraveling the plasmidome ofHelicobacter pylori: an unexplored source of potential pathogenicity
Authors: Mendoza-Guido Bradd , Romero-Carpio Juan D. , Molina-Castro Silvia 
Published: January 2025

2.AbstractHelicobacter pyloriis a significant human pathogen associated with gastric diseases, yet the role of plasmids in its pathogenicity remains underexplored. This study provides a comprehensive genomic and functional characterization of theH. pyloriplasmidome using publicly available plasmid sequences. Of 335 plasmids analyzed, 127 non-redundant representatives were selected for downstream analysis. MobMess network and Mash distance-based analyses suggest two major plasmid groups (G1 and G2) with distinct genomic and functional profiles. G1 plasmids were enriched in genes related to the Fic protein family and ABC transporters, potentially contributing to pathogenicity through post-translational modification and antibiotic extrusion, respectively. In contrast, G2 plasmids were predominantly associated with the Type IV Secretion System (T4SS) and conjugative elements, indicating a role in horizontal gene transfer. Notably, compound genes were linked to pathogenic proteins, including ClpP, VapD, and a putative vacuolating cytotoxin-related gene. This study underscores the functional diversity of theH. pyloriplasmidome and highlights the need for experimental validation to clarify its role in pathogenicity, antimicrobial resistance, and adaptability.3.Impact statementAlthoughHelicobacter pyloriis well-studied as the primary etiologic agent of gastric diseases, information about the role of plasmids in this species remains limited. This study contributes to microbial genomics by characterizing the genomic and functional diversity of theH. pyloriplasmidome available in public databases. Our findings highlight the importance of monitoring and conducting experimental assays to better understand the role of plasmids in pathogenic bacteria likeH. pylori, which may harbor genes related to pathogenicity and antimicrobial resistance.4.Data summaryThe authors confirm all supporting data, and protocols have been provided within the article or through supplementary data files. The code employed for bioinformatic analyses can be obtained from the corresponding author upon request.
Improved Identification of Host Cell Proteins in Monoclonal Antibodies by Combining Filter-Aided Sample Preparation and Native Digestion
Authors: Yang Yang , Wu Jing , Wang Fang , Lefers Mark 
Published: January 2025

AbstractHost cell proteins (HCPs) in biotherapeutics can present potential safety risks or compromise product stability at trace levels. Therefore, removal, testing, and characterization of HCPs are critical throughout biotherapeutic process development. While enzyme-linked immunosorbent assay (ELISA) is the gold standard for quantifying HCPs, it does not provide information on HCP identity. As a result, HCP analysis by liquid chromatography-mass spectrometry (LC-MS) has gained prominence for its ability to identifying HCPs. However, compared to ELISA’s parts-per-billion sensitivity, LC-MS is limited by its dynamic range, often unable to cover magnitude difference between HCP and biotherapeutic concentrations. Thus, an effective HCP enrichment method is highly desirable. In this study, we propose a new strategy for HCP identification that combines filter-aided sample preparation (FASP) with native digestion, followed by shotgun proteomics analysis. This approach improves mAb removal compared to standard native digestion, enabling greater HCP enrichment and identification. Our method detects all spiked proteins at 1 ppm and most at 0.5 ppm, ranging from 12 to 470 kDa, demonstrating broad molecular weight coverage of HCPs. A proof-of-concept analysis using the NISTmAb standard demonstrates that our filter-aided native digestion identifies 155 more HCPs than the standard native digestion. When applying this strategy to an in-house antibody with low amounts of HCPs, we can quantify HCPs at levels as low as 0.03 ppm, demonstrating the high sensitivity in HCP characterization.
NMDA-dependent coplasticity in VIP interneuron-driven inhibitory circuits
Authors: Jabłońska Jadwiga , Wiera Grzegorz , Mozrzymas Jerzy W. 
Published: January 2025

AbstractInhibitory plasticity is emerging as a key regulator of excitation/inhibition (E/I) balance, a fundamental determinant of brain network dynamics. While significant progress has been made in understanding inhibitory plasticity at synapses targeting excitatory principal neurons (I→E), the mechanisms and functional implications of plasticity at interneuron-interneuron (I→I) synapses remain largely unexplored. Herein, we investigated the properties and plasticity of inhibitory inputs from vasoactive intestinal peptide (VIP) interneurons ontostratum oriensinterneurons (soINs) in the hippocampal CA1 region. Using optogenetics, patch-clamp electrophysiology, and morphological reconstructions, we characterized the kinetics, short-term plasticity, and NMDA receptor-dependent long-term plasticity at VIP→soIN synapses in two distinctsoIN subtypes: fast-spiking (FS) and oriens-lacunosum moleculare (OLM)/bistratified interneurons. Optogenetically evoked VIP→soIN IPSCs showed faster rise times and slower decay kinetics in FS interneurons compared to OLM/bistratified cells, although both subtypes exhibited similar short-term plasticity profiles. Brief NMDA receptor activation (1 min) induced long-term depression (iLTD) at VIP→OLM/bistratified synapses, but not at VIP→FS synapses, underscoring subtype-specific plasticity. However, prolonged NMDA exposure (2 min) elicited iLTD in both interneuron subtypes. Interestingly, excitatory inputs tosoINs demonstrated NMDA-induced long-term potentiation (E→I LTP) after brief NMDA exposure, but not after prolonged application. Notably, coplasticity analysis in individualsoINs revealed asymmetric co-expression of I→I LTD and E→I LTP in OLM/bistratified interneurons. In contrast, FS interneurons exhibited a duration-dependent transition between asymmetric and symmetric coplasticity. These findings reveal a target-cell-specific landscape of inhibitory I→I plasticity and its co-expression with excitatory plasticity, highlighting VIP interneurons as key modulators of E/I balance within local hippocampal circuits.
Stress, Epigenetic Remodeling and FKBP51: Pathways to Chronic Pain Vulnerability
Authors: Morgan Oakley B. , Singleton Samuel , Hestehave Sara , Sarter Tim , Wozniak Eva , Mein Charles A , Hausch Felix , Bell Christopher G. , Géranton Sandrine M. 
Published: January 2025

AbstractStress is thought to contribute to the persistence of pain and comorbid anxiety, yet the underlying mechanisms remain unclear. In our pre-clinical model, sub-chronic stress exacerbated subsequently induced inflammatory pain and accelerated the development of comorbid anxiety. DNA methylation analysis of spinal cord tissue after stress exposure revealed hypomethylation in theFkbp5promoter site for the canonical FKBP51 transcript and other stress-related genes. However, most epigenetic changes in key regulatory regions did not correlate with changes in gene expression assessed by RNA sequencing, suggesting that stress exposure had remodeled the epigenome without altering gene activity and primed genes for hyper-responsiveness to future challenges. FKBP51 inhibition during stress exposure reduced the exacerbation of inflammatory pain by stress and reversed several stress-induced DNA methylation changes in promoter regions of genes associated with stress and nociception, includingRtn4, Cdk5andNrxn1, but notFkbp5. These results indicate that sub-chronic stress leads to the hypomethylation ofFkbp5and increased susceptibility to chronic pain driven by FKBP51, but reversingFkbp5hypomethylation is not necessary to prevent chronic pain vulnerability, which is likely driven by complex epigenetic regulation of multiple stress-regulated genes.
Ultimate light-shining-through-a-wall experiments to establish QCD axions as the dominant form of dark matter
Authors: Hoof Sebastian , Jaeckel Joerg , Lucente Giuseppe 
Published: January 2025

Establishing the axion as the dark matter (DM) particle after a haloscope discovery typically requires follow-up experiments to break the degeneracy between the axion’s coupling to photons and its local DM abundance. Given that a discovery would justify more significant investments, we explore the prospects of ambitious light-shining-through-a-wall (LSW) setups to probe the QCD axion band. Leveraging the excellent mass determination in haloscopes, we show how to design LSW experiments with lengths on the order of 100 km and suitably aligned magnetic fields with apertures of around 1 m to reach well-motivated axion models across up to four orders of magnitude in mass. Beyond presenting a concrete plan for postdiscovery experimental efforts, we briefly discuss complementary experiments and future directions beyond LSW experiments.

Published by the American Physical Society
2025
Detection of dilute axion stars with stimulated decay
Authors: Di Haoran , Shi Haihao , Yi Zhu 
Published: January 2025

The anomalous orbits of trans-Neptunian objects can be accounted for by the planet 9 hypothesis. One intriguing possibility is that planet 9 could be a dilute axion star captured by the Solar System, with the ratio of the axion star to dark matter being approximately 1/10. Although dilute axion stars can emit monochromatic signals through two-photon decay, the spontaneous decay signal is too weak to be detected by radio telescopes. However, we find that stimulated decay of the dilute axion star, which explains planet 9, can occur by directing a radio beam with a power of 50 MW into the star. The resulting echo can be detected by terrestrial telescopes such as SKA, FAST, ngLOBO, and LOFAR. Therefore, the dilute axion star can be distinguished from other planet 9 candidates, such as a primordial black hole or a free-floating planet captured by the Solar System.

Published by the American Physical Society
2025
Development of the logistics service quality framework for railway transportation in Tanzania
Authors: Taifa Ismail W.R. , Twaha Ibrahim 
Published: January 2025

PurposeThe research proposes a customised framework for improving logistics service quality (LSQ) in Tanzania's railway transportation, focusing on customer engagement and integrating customer-desired services.Design/methodology/approachThe survey method obtained data from railway customers regarding the LSQ offered. Both probability and purposive sampling techniques were used to get the sample size. The open- and closed-ended questionnaires gathered the pertinent data. The data were analysed qualitatively and quantitatively using the IBM® SPSS® 21.0 and AMOS 21.0 software packages, respectively. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed to analyse data and establish relationships between variables.FindingsThis study anticipated that the LSQ framework during the period of reviewing literature included three variables for freight transporting customers (tangible components, ways of fulfilment and information actions) and eight variables for passengers (tangible, reliability, assurance, responsiveness, comfort, empathy, connection and convenience). EFA and CFA dropped some factors. The retained factors were used as inputs to develop a framework. The qualitative analysis also established the improvement of customer’s desired services (CDS) and LSQ, which were the framework's processes for improving the LSQ. Ultimately, the study developed the LSQ framework for railway transportation.Research limitations/implicationsThe study was conducted on Tanzania’s railways, which incorporated challenges in the Tanzanian context. However, many challenges in the developing countries are relatively the same. Therefore, modifications can be made to adopt the developed framework and be used in other countries to cover the geographical and other challenges in particular countries.Originality/valueTanzania’s railway infrastructures are somehow not fully utilised to meet the actual needs of the transportation sector. For example, one of the railway companies has a built capacity of 4 million tonnes carrying capacity per year, but the actual cargo transported by the railway is 200,000 tonnes. This comes from several challenges within the railway companies, including the quality of their services, thus leading to a need to develop a LSQ framework.
Examining the impact of fun in the workplace in hospitality internships
Authors: Tews Michael J. , Hoefnagels Ankie , Pons Sydney , Beaumont-Perez Fanny 
Published: January 2025

PurposeThis study examines the importance of fun in the workplace within the context of hospitality internships. It aims to determine the impact of three dimensions of fun – fun activities, coworker socializing and manager support for fun – on the perceived value of internships and students' commitment to pursuing a career in the hospitality industry.Design/methodology/approachThe study involved a sample of 253 hospitality management students in The Netherlands. Data were collected through an online survey and analyzed using multiple regression to assess the relationships between fun in the workplace, internship value and industry commitment. The study also considered the influence of job characteristics, social support and work-life conflict.FindingsThe results indicated that coworker socializing had a positive relationship with both internship value and industry commitment. Manager support for fun positively influenced internship value but had a negative relationship with industry commitment. Fun activities did not significantly impact either outcome. Additionally, skill variety was found to be crucial for internship value, particularly for operational interns.Practical implicationsThe findings suggest that while fun in the workplace can enhance the internship experience, it should not overshadow other critical factors such as skill variety, supervisor support and the presence of role models. Internship programs should focus on providing diverse and challenging tasks to maximize perceived value and industry commitment among students.Originality/valueThis study extends the research on workplace fun by focusing on its role in the internship experience within the hospitality industry. It provides insights into how different dimensions of fun affect internship outcomes and highlights the importance of balancing fun with other essential aspects of the work environment to foster positive student experiences and career aspirations.