bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying genomic surveillance gaps in Africa for the global public health response to West Nile Virus
Authors: Moir Monika , Sitharam Nikita , Hofstra Marije , Dor Graeme , Mwanyika Gaspary , Ramphal Yajna , Reichmuth Martina L. , James San Emmanuel , Gifford Robert , Wilkinson Eduan , Tshiabuila Derek , Preiser Wolfgang , Konou Abla Ahouefa , Bitew Molalegne , Onoja Bernard Anyebe , Paganotti Giacomo Maria , Abera Adugna , Maror James Ayei , Kayiwa John , Abuelmaali Sara , Lusamaki Eddy Kinganda ,   CLIMADE Consortium, Venter Marietjie , Burt Felicity , Baxter Cheryl , Lessells Richard , de Oliveira Tulio , Tegally Houriiyah 
Published: January 2025

SummaryBackgroundWest Nile Virus (WNV) is a zoonotic flavivirus of significant One Health relevance and is classified as a priority pathogen with a high-risk of causing public health emergencies of global concern. WNV is endemic to Africa; however, the availability of genomic sequences from the continent remains limited.MethodsWe review the extent of polymerase chain reaction testing and genomic sequencing of WNV conducted across Africa. Using phylogeographic methods, we map the spatiotemporal spread of the virus across the continent and globally.FindingsOur study shows that WNV has been detected in 39 African countries (including Comoros, Seychelles, and Mauritius), the Canary Islands, and Réunion Island. Publications including molecular data originate from 24 countries; however, genomic sequences are publicly available for only 16 countries. We identify regions with detected viral circulation but lacking molecular surveillance. Further, we list such regions that overlap with Key Biodiversity Areas (sites harbouring significant bird diversity) as they may host high viral circulation, and high human population density that may be susceptible to spillover.InterpretationWe recognise significant knowledge gaps on the true disease burden, molecular epidemiology, and distribution of WNV in Africa. Addressing these gaps requires an integrated One Health surveillance approach which is challenging to establish. We propose three key surveillance needs as potential starting points to improve our understanding of the virus in Africa to strengthen the global public health response to this disease.FundingRockefeller Foundation, the National Institute of Health USA, Institute of Human Virology Nigeria, Global Health EDCTP3 Joint Undertaking, the Health Emergency Preparedness and Response Umbrella Program, managed by the World Bank Group, the Medical Research Foundation, and the Wellcome Trust.
Molecular and evolutionary determinants for protein interaction within a class II aldolase/Adducin domain
Authors: Seheon Marina E. , Parra Amalia S. , Johnston Christopher A. 
Published: January 2025

ABSTRACTThe appearance of modular protein interaction domains represents a crucial step in the evolution of multicellularity. For example, the class II aldolase domain (ALDODOM) found within the Adducin gene family shares sequence and structural homology to a glycolytic aldolase enzyme found in many evolutionarily ancient phyla. ALDODOMis best known for direct binding to actin filaments through a tetrameric assembly. Molecular details for additional ALDODOMinteractions have not been resolved, nor have the sequence changes underlying the dramatic functional switch in the aldolase protein fold. Here we explore the molecular basis for the interaction between ALDODOMof Hts (DrosophilaAdducin) and the mitotic spindle regulator, Mud. Our results suggest a distinct mode of interaction, as conserved actin-contacting residues on the tetramer surface were found dispensable for Mud binding. Instead, we identify a critical role for the ALDODOMC-terminal helix (CThelix), along with residues from the adjacent protomer that occur at a tetrameric interface conserved among domains and a subgroup of aldolase enzymes (ALDOENZs). Truncation of the CThelix from bacterial ALDOENZ, or chimeric fusion with that from Hts, confers ALDODOM-like Mud binding. Sequence database analyses suggest ALDODOMfunction may have arisen in the primitive metazoan phylum,Placozoa, which contain both an aldolase enzyme and domain capable of Mud binding. Finally, we identify a single, conserved arginine-to-glycine change that also permits Mud binding within the bacterial ALDOENZ. Our work provides molecular and evolutionary insights into the function of a conserved protein-binding domain within multicellular organisms.
Synergizing Network Pharmacology and Pan-Cancer Analysis in TCM Repositioning for Tumor Therapy
Authors: Yang Dongli , Hu Xiyun , Liu Yong , Liao Yong , Fahira Aamir , Wang Lishan , Shahab Muhammad , Ouyang Defang , Kuang Weihong , Huang Zunnan 
Published: January 2025

AbstractBackgroundRepositioning Traditional Chinese Medicine (TCM) for cancer treatment, addressing heterogeneity through synergistic effects, aligns with the evolving trend of combination therapy. However, the complexity of TCM and the lack of methodology hinders the elucidation of TCM treatment mechanisms and potential indications. The research aims to construct develop a comprehensive method combining network pharmacology and pan-cancer analysis (NetPharm-PanCan) for TCM repositioning, exemplified by the Astragali Radix-Curcumae Rhizoma (ARCR) herb pair.MethodThe TCM-component-gene network was constructed using Cytoscape3.7.2 with gene screening based on components from TCMSP and targets predicted via the Swiss Target Prediction database. The core gene set of the ARCR (CGSARCR) was identified by analyzing network via the dual algorithm, namely Degree and MCODE followed by GO and KEGG enrichment analyses. The pan-cancer analysis encompassing Gene Set Variation Analysis (GSVA), immune infiltration correlation, cancer pathway analysis, and Gene Set Enrichment Analysis (GSEA) was unveiled to identify the potential indications. Multivariate cox regression analysis was employed for identifying prognostic genes, followed by the modeling for potential therapeutic indications using the R software. The Metescape database was harnessed to reveal similarities and differences in the mechanisms for prognostic genes associated with potential indications. The XGBoost algorithm was used to construct an indication prediction system according to the analysis results above.ResultThe CGSARCRcomprises 28 genes targeting all ARCR components. The pan-cancer analysis revealed that the CGSARCR showed significantly higher tumor scores than normal tissue scores across nine different types of cancer, including THCA, KIRC, LUAD, COAD, BRCA, STAD, ESCA, and others. The CGSARCRcorrelated strongly with cancer-related pathways and the immune microenvironment. Prognostic models evaluate the potential of these indications as follows: THCA> KIRC> LUAD> COAD> BRCA> STAD> ESCA, with enrichment analysis suggesting KIRC and LUAD as the most potential indications of ARCR. The XGBoost-based system achieved high predictive accuracy (training AUC: 0.985, testing AUC: 0.96, training logloss: 0.21, testing logloss: 0.25).ConclusionThe NetPharm-PanCan method provides a robust, network-based pan-cancer analysis framework for TCM repositioning in cancer research. It provides theoretical foundations and practical tools for TCM-based drug development, with potential applicability to broader drug repurposing efforts.
Proteomic profiling of advanced hepatocellular carcinoma identifies predictive signatures of response to treatments
Authors: Delamarre Adèle , Decraecker Marie , Blanc Jean-Frédéric , Tommaso Sylvaine Di , Dourthe Cyril , Dupuy Jean-William , Moreau Mélanie , Allain Nathalie , Mahouche Isabelle , Giraud Julie , Bénard Giovanni , Lalou Claude , Pinson Benoît , Bioulac-Sage Paulette , Toulouse Caroline , Morisset Audrey , Boursier Jérôme , Bail Brigitte Le , Raymond Anne-Aurélie , Saltel Frédéric 
Published: January 2025

AbstractPurposeHepatocellular carcinoma (HCC) is the most common form of liver cancer with a bad prognosis in case of advanced HCC, only eligible for palliative systemic therapies. After a decade of exclusive sorafenib monotherapy, with a response rate of <10%, the advent of immunotherapies represents a revolution in HCC. The combination of atezolizumab/bevacizumab is recommended as the first-line systemic treatment, with a response rate around 30%. However, there are currently no predictive factors for response to these treatment options.Experimental DesignWe profiled, by high-resolution mass spectrometry-based proteomics combined with machine learning analysis, a selected cohort of fixed biopsies of advanced HCC. We grouped subjects according to their objective response to treatments, corresponded to a tumor regression vs tumor progression at 4 months after treatment.ResultsWe generated a proteome database of 50 selected HCC samples. We compared the relative protein abundance between tumoral and non-tumoral liver tissues from advanced HCC patients treated. The clear distinction of these two groups for each treatment is based on deregulation for 141 protein or 87 for atezolizumab/bevacizumab and sorafenib treatment, respectively. These specific proteomic signatures were sufficient to predict the response to treatment, and revealed biological pathways involved in treatment’s resistance. Particularly, we validated a shift in tumor cell metabolism with an immunosuppressive environment involved in the resistance to atezolizumab/bevacizumab combination.ConclusionsWe performed an in-depth analysis of quantitative proteomic data from HCC biopsies to predict the treatment response to advanced HCC giving the ability to optimize patient management.
ORP2 regulates free cholesterol accumulation in hepatocytes during MASH
Authors: Wu Jin , Zhao Yudi , Qiu Liwen , Liang Yan , Chen Qiaoli , Wang Xiaowei , Gu Jingwen , Wang Hong-Yu , Liu Yang , Wu Xiaoqin , Chen Shuai , Chen Feng-Jung , Gao Mingming , Yang Hongyuan 
Published: January 2025

AbstractBackgroundCholesterol crystals in hepatocytes are known to strongly associate with human Metabolic Dysfunction-Associated Steatohepatitis (MASH). However, it remains unclear which molecular pathway(s) regulates free cholesterol accumulation, and therefore the formation of cholesterol crystals in hepatocytes. In cultured cell lines, oxysterol-binding protein-related protein 2 (ORP2) functions to deliver cholesterol to the plasma membrane from internal organelles.MethodsHere, we generated liver-specific ORP2 knockout (ORP2-LKO) mice and characterized their metabolic phenotypes on chow and high fat diet.ResultsThe ORP2-LKO mice developed much more severe hepatic steatosis than wild type mice after high-fat diet feeding. They also demonstrated more severe liver inflammation and damage. Notably, free but not esterified cholesterol, as well as cholesterol crystals accumulated in ORP2-LKO liver. The expression of Cyp7a1 was significantly upregulated in ORP2-LKO liver, accompanied with accumulation of taurocholic acid. Our results thus unveil an importantin vivofunction of ORP2 in preventing free cholesterol from accumulating in mouse liver.Conclusionsour results suggest that impaired cholesterol trafficking may enhance the deposition of cholesterol crystals in hepatocytes, promoting the development of MASH.
Biofilm Forming Capacity, Sanitizer Tolerance, and Genetic Characterization of Persistent and Non-PersistentListeria monocytogenesfrom Artisanal Cheese Processing Environments
Authors: Aboagye Eurydice , Forauer Emily , Gilmour Aislinn , Blackwell Hannah B. , Cushman Lara , Herren Calleigh , Denaro Sophia , Felten Lily , Ballard McKenzie , Etter Andrea 
Published: January 2025

AbstractListeria monocytogenesis known to colonize food production environments and cross-contaminate finished foods. We investigated 30L. monocytogenescollected from artisan cheese production facilities in Vermont from 2006-2008 for sanitizer tolerance, biofilm formation capacity, biofilm architecture, and tolerance to sanitizers of mature biofilms. Sixteen of these isolates represented a putatively persistent ribotype (DUP-1042B) found in one facility over two years. Isolates of the putatively persistent ribotype all aligned into ST191 and were 0-6 SNPs different, confirming they represented a persistent strain. We found no significant differences in sanitizer tolerance or crystal assay-based attachment capacity between persistent and non-persistent strains. However, using scanning electron microscopy, we found that isolates FML-10 and FML-19 formed substantially denser biofilms after 10 days on stainless steel. Ten-day old biofilms were highly resistant to sanitizers; neither quaternary ammonium nor sodium hypochlorite-based sanitizers achieved an EPA-recommended 6-log reduction. More EPS was found in low-nutrient biofilm conditions; thus, non-food contact surfaces in cheese environments may induce formation of biofilms with high sanitizer tolerance. Our results highlight the importance of regular environmental testing and strain typing for rapid detection ofL. monocytogenescolonization attempts while they can still be removed without major renovations or equipment replacement.HighlightsIsolates from persistent ribotype DUP-1042B/ST191 were within 6 SNPs of each otherTwo isolates from ST191 made dense biofilms in nutrient rich conditionsMore EPS was produced in nutrient-poor conditionsMature biofilms of all isolates were highly resistant to QAC and SH sanitizersImportanceThis study identifies strategies used by a set of persistently colonizingL. monocytogenesisolated from an artisanal cheese producer in Vermont, finding that some persistently colonizing isolates had high biofilm forming capacity, which may have contributed to their persistence.
A Novel Silver-Ruthenium-Based Antimicrobial Kills Gram-Negative Bacteria Through Oxidative Stress-Induced Macromolecular Damage
Authors: Tawiah Patrick Ofori , Gaessler Luca Finn , Anderson Greg M. , Oladokun Emmanuel Parkay , Dahl Jan-Ulrik 
Published: January 2025

ABSTRACTAmplified by the decline in antibiotic discovery, the rise of antibiotic resistance has become a significant global challenge in infectious disease control. ExtraintestinalEscherichia coli(ExPEC), known to be the most common instigators of urinary tract infections (UTIs), represent such global threat. Novel strategies for more efficient treatments are therefore desperately needed. These include silver nanoparticles, which have been used as antimicrobial surface-coatings on catheters to eliminate biofilm-forming uropathogens and reduce the risk of nosocomial infections. AGXX® is a promising silver coating that presumably kills bacteria through the generation of reactive oxygen species (ROS) but is more potent than silver. However, neither is AGXX®’s mode of action fully understood, nor have its effects on Gram-negative bacteria or bacterial response and defense mechanisms towards AGXX® been studied in detail. Here, we report that the bactericidal effects of AGXX® are primarily based on ROS formation, as supplementation of the media with a ROS scavenger completely abolished AGXX®-induced killing. We further show that AGXX® impairs the integrity of the bacterial cell envelope and causes substantial protein aggregation and DNA damage already at sublethal concentrations. ExPEC strains appear to be more resistant to the proteotoxic effects of AGXX® compared to non-pathogenicE. coli,indicating improved defense capabilities of the uropathogen. Global transcriptomic studies of AGXX®-stressed ExPEC revealed a strong oxidative stress response, perturbations in metal homeostasis, as well as the activation of heat shock and DNA damage responses. Finally, we present evidence that ExPEC counter AGXX® damage through the production of the chaperone polyphosphate.
An Entropy-Based Approach to Model Selection with Application to Single-Cell Time-Stamped Snapshot Data
Authors: Stewart William CL , Jayaprakash Ciriyam , Das Jayajit 
Published: January 2025

AbstractRecent single-cell experiments that measure copy numbers of over 40 proteins in individual cells at different time points [time-stamped snapshot (TSS) data] exhibit cell-to-cell variability. Because the same cells cannot be tracked over time, TSS data provide key information about the time-evolution of protein abundances that could yield mechanisms that underlie signaling kinetics. We recently developed a generalized method of moments (GMM) based approach that estimates parameters of mechanistic models using TSS data. However, when multiple mechanistic models potentially explain the same TSS data, selecting the best model (i.e., model selection) is often challenging. Popular approaches like Kullback-Leibler divergence and Akaike’s Information Criterion are difficult to implement because the distribution that gave rise to the “noisy” data is only known numerically and approximately. To perform model selection in this situation, we introduce an entropy-based approach that incorporates our GMM based parameter estimation and commonly used estimators in kernel density estimation. Using simulated TSS data, we show that our approach can select the “ground truth” from a set of competing mechanistic models. Furthermore, we use a bootstrap procedure to compute model selection probabilities, which can be useful when measuring the relative support of a candidate model.
Emergence of a contrast-invariant representation of naturalistic texture in macaque visual cortex
Authors: Lee Gerick M. , Majaj Najib J. , Deliz C. L. Rodríguez , Kiorpes Lynne , Movshon J. Anthony 
Published: January 2025

ABSTRACTSensory stimuli vary across a variety of dimensions, like contrast, orientation, or texture. The brain must rely on population representations to disentangle changes in one dimension from changes in another. To understand how the visual system might extract separable stimulus representations, we recorded multiunit neuronal responses to texture images varying along two dimensions: contrast, a property represented as early as the retina, and naturalistic statistical structure, a property that modulates neuronal responses in V2 and V4, but not in V1. We measured how sites in these 3 cortical areas responded to variation in both dimensions. Contrast modulated responses in all areas. In V2 and V4, the presence of naturalistic structure both modulated responses and increased contrast sensitivity. Tuning for naturalistic structure was strongest in V4; tuning in both dimensions was most heterogeneous in V4. We measured how well populations in each area could support the linear readout of both dimensions. Populations in V2 and V4 could support the linear readout of naturalistic structure, but only in V4 did we find evidence for a robust representation that was contrast-invariant.Significance StatementSingle neurons in visual cortex respond selectively to multiple stimulus dimensions, so signals from single neurons cannot distinguish changes in one dimension from changes in another. We measured responses from simultaneously recorded neural populations in three hierarchically linked visual areas – V1, V2, and V4 – using texture stimuli that varied in two dimensions, contrast and naturalistic image structure. We used linear decoding methods to extract information about each dimension. In all three areas, contrast could be decoded independently of image structure. Only in V4, however, could image structure be decoded independently of contrast. The reason is that selectivity for texture and contrast in V4 was much more diverse than in V1 or V2. This heterogeneity allows V4 to faithfully represent naturalistic image structure independent of contrast.
Parenteral Vaccination with recombinant EtpA glycoprotein impairs enterotoxigenicE. colicolonization
Authors: Vickers Tim J , Buckley David , Khatoon Nazia , Sheikh Alaullah , Setu Bipul , Berndsen Zachary T. , Fleckenstein James M. 
Published: January 2025

abstractEnterotoxigenicE. coli(ETEC) cause hundreds of millions of cases of acute diarrheal illness in low-middle income regions, disproportionately in young children. To date there is no licensed, broadly protective vaccine to protect against these common but antigenically heterogeneous pathogens. One of the more highly conserved antigens of ETEC, EtpA, is an extracellular glycoprotein adhesin that preferentially binds to blood group A glycans on intestinal epithelia. EtpA contributes to increased severity of illness in blood group A individuals, elicits robust serologic and fecal antibody responses following infection, and has been associated with protection against subsequent infection. However, its utility as a protective antigen needs further examination. In the present studies we examined whether parenteral vaccination with recombinant EtpA (rEtpA) could afford protection against intestinal colonization in a murine model of ETEC infection. Here, we demonstrate that intramuscular vaccination with rEtpA when adjuvanted with double mutant LT (dmLT) primes IgG predominant mucosal antibody responses to ETEC challenge. Notably, however, both antibody levels and avidity, as well as protection were dependent on vaccination schedule. Likewise, by electron microscopy polyclonal epitope mapping (EMPEM) we observed a greater diversity of epitopes targeted by antibodies after a more protracted vaccination schedule. Next, we explored the utility of IM immunization with alum-adjuvanted rEtpA. This elicited strong serologic and fecal IgG responses. Although accompanied by negligible IgA mucosal responses, EtpA alum-adjuvanted IM vaccination nevertheless protected against ETEC intestinal colonization. Collectively, these data suggest that EtpA could expand the portfolio of antigens targeted in ETEC subunit vaccine development.