bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of different synonymous codon substitution strategies on SARS-CoV-2 nucleocapsid protein expression inEscherichia coli
Authors: Bello Adebayo J. , Omotuyi Ayomide O. , Oladapo Olajumoke B. , Adekunle Adegbayi A. , Udechime Kingsley U. , Akinwande Abdulzamad B. , Odewale Adeyemi F. , Davis Eban , Adamson Olawale , Folarin Onikepe , Okpuzor Joy , Minari Joseph B. 
Published: November 2024

AbstractSARS-CoV-2 is an enveloped, positive-strand RNA virus. The virus nucleocapsid (N) protein is stable, conserved, highly immunogenic, and less prone to mutation during infection, making it a key antigen inin vitrodiagnosis, vaccine development, immunological and structural studies. synonymous codon substitution, a gene engineering method in synthetic biology is the approach to improve the codon composition of a recombinant gene based on various criteria without altering the amino acid sequence. We analyzed the influence of different synonymous codon substitution strategies on SARS-CoV-2 N-protein expression inE. coli. Using JCat and Genewiz codon optimization tools, and a codon harmonization (CH) tool, we predicted and compared how different parameters such as GC content, Codon Adaptation Index, codon quality and number of rare codons present in these sequences affect the N-protein expression. Our prediction also shows that Minimum Free Energy (MFE) and RNA structure of N-term and C-tail of the N-protein coding sequence influence protein folding. We also demonstrated that the SR-rich region of the N-protein may contribute to slowing down the elongation rate during translation. In general, Genewiz optimization shows better result from our analysis. This work presents a fundamental analysis of how different optimization tools affect SARS-CoV-2 N-protein expression and folding and suggests a basic approach to choosing the best strategy for optimal expression and folding of the protein for further studies.Key pointsCodon substitution affects SARS-CoV-2 nucleocapsid protein expression.Parameters of different synonymous substitution tools impact variation the SARS-CoV-2 protein expression.RNA structures of the nucleocapsid N-term and C-tail impact the RNA stability, protein expression and folding.The SR-rich region of the nucleocapsid protein may slow down elongation rate during translation.The synonymous codon substitution predicts variation in elongation rhythm pattern.
Single-cell atlas of the human immune system reveals sex-specific dynamics of immunosenescence
Authors: Sopena-Rios Maria , Ripoll-Cladellas Aida , Omidi Fatemeh , Ballouz Sara , Hernandez Jose Alquicira- , Oelen Roy , Franke Lude , van der Wijst Monique G.P. , Powell Joseph E. , Melé Marta 
Published: November 2024

AbstractImmunosenescence, the gradual deterioration of the immune system with age, leads to an increased susceptibility to a range of diseases associated with immune dysfunction. Notably, sex is an important variable underlying how immune aging unfolds, as, for instance, autoimmunity develops with aging differently between males and females. Even though some clinical and molecular differences have been identified between male and female immunosenescence, it is not known to what extent sex affects the dynamic composition of immune cells over time. Here, we analyze a large single-cell RNA-sequencing dataset of peripheral blood mononuclear cells from a sex-balanced cohort of 982 human donors providing novel transcriptional and cellular insights into immune aging at an unprecedented resolution. We uncover that aging induces cell type-dependent and sex-specific transcriptional shifts that translate into a differential abundance of distinct immune cell subpopulations. These shifts predominantly involve translation-related genes, indicating a strong link between transcriptional and translational throughput with cell function and consequent immune cell composition. This sexual dimorphism overlaps known autoimmune disease-related genetic variants and results in the differential enrichment of functionally distinct immune populations. Specifically, we uncover that a cytotoxic CD8+ T effector memory subpopulation with an NK-like phenotype accumulates with age only in females and identify a distinct B cell subpopulation that expands with age exclusively in males. These cell subpopulations represent novel sex-specific hallmarks of immune aging. Our findings underscore the hidden complexity of immune aging and demonstrate the value of high-resolution, single-cell analyses in large population cohorts. This research paves the way for future sex-specific interventions targeting immunosenescence to ultimately promote a personalized approach to foster healthy aging.
Metaproteomic profiling of the secretome of a granule-formingCa. Accumulibacter enrichment
Authors: van Olst Berdien , Eerden Simon A. , Eštok Nella A. , Roy Samarpita , Abbas Ben , Lin Yuemei , van Loosdrecht Mark C.M. , Pabst Martin 
Published: November 2024

ABSTRACTExtracellular proteins are supposed to play crucial roles in the formation and structure of biofilms and aggregates. However, often little is known about these proteins, in particular for microbial communities. Here, we use two advanced metaproteomic approaches to study the extracellular proteome in a granularCandidatusAccumulibacter enrichment as a proxy for microbial communities that form solid microbial granules, such as used in biological wastewater treatment. Limited proteolysis of whole granules and metaproteome isolation from the culture’s supernatant successfully identified over 50% of the protein biomass to be secreted. Moreover, structural and sequence-based classification identified 387 proteins, corresponding to over 50% of the secreted biomass, with characteristics that could aid the formation of aggregates, including filamentous, beta-barrel containing, and cell surface proteins. However, while most filamentous proteins originated fromCa. Accumulibacter, among others cell surface proteins did not. This suggests that not only a range of different proteins, but also multiple organisms contribute to granular biofilm formation. Therefore, the obtained extracellular metaproteome data from the granularCa. Accumulibacter enrichment provides a resource for exploring proteins that potentially support the formation and stability of granular biofilms, whereas the demonstrated approaches can be applied to explore biofilms of microbial communities in general.SIGNIFICANCEBiofilm-forming microbial communities are widespread and pose both challenges and opportunities in various settings in life. Structure-providing, extracellular proteins likely play a crucial role in the formation of the biofilm matrix, but these proteins are challenging to characterise due to the dynamic and complex nature of these communities. We used two advanced metaproteomic approaches to enrich for the extracellular proteins in a granule-formingCandidatusAccumulibacter enrichment culture as a proxy for granule-forming communities present in wastewater treatment plants. The extracellular proteins were additionally classified using structure and sequence-based annotation tools, which identified multiple different protein categories that potentially aid in granule formation, but also may provide structure to the biofilm matrix. Interestingly, although the granules were highly enriched forCa. Accumulibacter, several structure-providing protein categories originated from other organisms. The obtained metaproteomic data contribute to the understanding of proteins and processes that are potentially involved in granule formation. This could further help to optimise processes involving granular biofilms and identify candidates for the recovery of novel biopolymers for biotechnological applications.
Speech-in-noise perception across the lifespan: A comparative study in Mongolian gerbils and humans
Authors: Jüchter Carolin , Chi Chieh-Ju , Beutelmann Rainer , Klump Georg Martin 
Published: November 2024

AbstractMany elderly listeners have difficulties with speech-in-noise perception, even if auditory thresholds in quiet are normal. The mechanisms underlying this compromised speech perception with age are still not understood. For identifying the physiological causes of these age-related speech perception difficulties, an appropriate animal model is needed enabling the use of invasive methods. In a comparative behavioral study, we used young-adult and quiet-aged Mongolian gerbils as well as young and elderly human subjects to investigate the age-related changes in speech-in-noise perception evaluating whether gerbils are an appropriate animal model for the age-related decline in speech-in-noise processing of human listeners.Gerbils and human subjects had to report a deviant consonant-vowel-consonant combination (CVC) or vowel-consonant-vowel combination (VCV) in a sequence of CVC or VCV standards, respectively. The logatomes were spoken by different speakers and masked by a steady-state speech-shaped noise. Response latencies were measured to generate perceptual maps employing multidimensional scaling, visualizing the subjects’ internal representation of the sounds. By analyzing response latencies for different types of vowels and consonants, we investigated whether aging had similar effects on speech-in-noise perception in gerbils compared to humans. For evaluating peripheral auditory function, auditory brainstem responses and audiograms were measured in gerbils and human subjects, respectively.We found that the overall phoneme discriminability in gerbils was independent of age, whereas consonant discriminability was declined in humans with age. Response latencies were generally longer in aged than in young gerbils and humans, respectively. Response latency patterns for the discrimination of different vowel or consonant types were different between species, but both gerbils and humans made use of the same articulatory features for phoneme discrimination. The species-specific response latency patterns were mostly unaffected by age across vowel types, while there were differential aging effects on the species-specific response latency patterns of different consonant types.
Bacterial warfare is associated with virulence and antimicrobial resistance
Authors: Sharp Connor , Foster Kevin 
Published: November 2024

AbstractBacteria have evolved a diverse array of mechanisms to inhibit and kill competitors, commonly known as bacterial weapons. However, why some bacteria carry weapons while others do not remains poorly understood. Here we explore this question using the bacteriocins ofE. colias a model system, which are both well studied and have large well-annotated genomic resources. While bacteriocins are found widely acrossE. colistrains, we find that carriage is particularly associated with pathogenic extra-intestinal (ExPEC) strains, including many clinically-important pandemic strains. These pathogenic strains commonly carry large plasmids that encode the bacteriocins but also virulence factors, including siderophores, and antimicrobial resistance mechanisms. Across allE. colistrains, we find many orphan immunity proteins, which protect against bacteriocins and suggest that bacterial warfare is important in nature. We also present evidence that bacteriocin toxins readily move between strains via plasmid transfer and even between plasmids via transposons. Finally, we show that severalE. colibacteriocins are widely shared with the pathogenSalmonella enterica, further cementing the link to virulence. Our work suggests that the bacteriocins ofE. coliare important antibacterial weapons for dangerous antimicrobial-resistant strains.
AI-Augmented Physics-Based Docking for Antibody-Antigen Complex Prediction
Authors: Gaudreault Francis , Sulea Traian , Corbeil Christopher R. 
Published: November 2024

AbstractPredicting the structure of antibody-antigen complexes is a challenging task with significant implications for the design of better antibody therapeutics. However, the levels of success have remained dauntingly low, particularly when high standards for model quality are required, a necessity for efficient antibody design. Artificial intelligence (AI) has significantly impacted the landscape of structure prediction for antibodies, both alone and in complex with their antigens. We utilized AI-guided antibody modeling tools to generate ensembles displaying diversity in the complementarity-determining region (CDR) and integrated those into our previously published AlphaFold2-rescored docking pipeline, a strategy called AI-augmented physics-based docking. We highlight that the quality of the ensemble is crucial for docking performance, that including too many models can be detrimental and that prioritization of models is essential for achieving good performance. In this study, we also compare docking performance with AlphaFold, the new benchmark in the field. We distinguish between two types of success tailored to specific downstream applications: 1) criteria sufficient for epitope mapping, where gross quality is adequate and can complement experimental techniques, and 2) criteria for producing higher-quality models suitable for engineering purposes. Our results robustly demonstrate the advantages of AI-augmented docking over AlphaFold2, further accentuated when higher standards in quality are imposed. Docking performance is noticeably lower than the one of AlphaFold3 in both epitope mapping and antibody design. While we observe a strong dependence on CDR-H3 length for physics-based tools on their ability to successfully predict, this helps define an applicability range where physics-based docking can be competitive to AlphaFold3.
Use of Hypochlorous Acid in Infections: Bibliometric Analysis of Scientific Literature
Authors: Ateş Fatih M. 
Published: November 2024

AbstractBackgroundHistorically, chemicals such as alcohols, aldehydes, chlorinated compounds and hypochlorous acid have been used to eliminate or inactivate infectious agents. Since bibliometrics is a powerful tool for uncovering scientific literature, we decided to conduct a bibliometric analysis of the literature on the use of hypochlorous acid in infections. Emerging trends and common patterns in research were explored, collaborations and networks were monitored and future directions were predicted.MethodsThe Scopus database was searched for documents published between 1982 and 2024 using the keywords “hypochlorous acid”, “infection” and “use”. Data analysis was performed using R-Studio 2024.09.0 Build 375 software with a machine learning bibliometric method based on the bibliometrix R package. The most relevant authors were measured by the number and fractional number of documents written. Author productivity was analyzed with Lotka’s law. Bradford’s law was applied to identify the core of journals focusing on the topic under consideration. The field of mainstream themes included isolated topics (niche themes), new topics (emerging themes), hot topics (engine themes) and core topics (core themes).ResultsA total of 574 documents were found, the vast majority of which were original articles (74%). The annual growth rate was 5.08%. Overall, 424 journals published more than one document. Most of the corresponding authors work in the United States. Neutrophils, animals and hydrogen peroxide are emerging themes, while hypochlorous acid, human, article represent the basic themes.Conclusions/Applications for PracticeThe interests of infection specialists have diversified over time and metabolism, reactive oxygen metabolites, anti-infective agents have been added.
Topoisomerase IIb binding underlies frequently mutated elements in cancer genomes
Authors: Uusküla-Reimand Liis , Lee Christian A. , Oh Robin H. , Klein Zoe P. , Adler Nina , Alvi Sana Akhtar , Langille Ellen , Pasini Elisa , Cheng Kevin C. L. , Abd-Rabbo Diala , Hou Huayun , Tsai Ricky , Bhat Mamatha , Schramek Daniel , Wilson Michael D. , Reimand Jüri 
Published: November 2024

ABSTRACTType-II topoisomerases resolve topological stress in DNA through controlled double-strand breaks. While TOP2A is a chemotherapy target in proliferating cells, the ubiquitously expressed TOP2B is a potential off-target. Here we explore roles of TOP2B in mutagenesis by generating DNA-binding maps of TOP2B, CTCF, and RAD21 in human cancer samples and analysing these maps for driver mutations and mutational processes in 6500 whole cancer genomes. TOP2B-CTCF-RAD21 and TOP2B-RAD21 sites are enriched in somatic mutations and structural variants (SVs), especially at evolutionary conserved sites displaying high transcription and long-range chromatin interactions. TOP2B binding underlies SVs and hotspot mutations in cancer-driving genes such asTP53,MYC,FOXA1, andVHL, and many cis-regulatory elements. We show that the TOP2B-bound mutational hotspot atRMRPdrives tumor initiation and growthin vivo. These data highlight TOP2B as a protector of the genome from topological challenges whose aberrant activity promotes driver and passenger mutations in cancer genomes.
Multi-dimensional social relationships shape social attention in monkeys
Authors: Liu Sainan , Huang Jiepin , Chen Suhao , Platt Michael , Yang Yan 
Published: November 2024

AbstractSocial relationships guide individual behavior and ultimately shape the fabric of society. Primates exhibit particularly complex, differentiated, and multidimensional social relationships, which form interwoven social networks, reflecting both individual social tendencies and specific dyadic interactions. How the patterns of behavior that underlie these social relationships emerge from moment-to-moment patterns of social information processing remains unclear. Here, we assess social relationships among a group of four monkeys, focusing on aggression, grooming, and proximity. We show that individual differences in social attention vary with individual differences in patterns of general social tendencies and patterns of individual engagement with specific partners. Oxytocin administration altered social attention and its relationship to both social tendencies and dyadic relationships, particularly grooming and aggression. Our findings link the dynamics of visual information sampling to the dynamics of primate social networks.
Engineered HMGB1 construct with tandem HMG B domains promotes tissue regeneration without potential for deleterious inflammation or thrombosis
Authors: Viñals Guitart Álvaro , Lee Carl , Espírito Santo de Fonseca Ana , Ruan Jia-Ling , Redfield Christina , Yue Wyatt , Burgess-Brown Nicola , Fedorov Oleg , Nanchahal Jagdeep 
Published: November 2024

AbstractHigh Mobility Group Box 1 protein in its fully-reduced state (FR-HMGB1) binds to CXC Ligand 12 (CXCL12) and signals through CXC Receptor 4 (CXCR4) to transition stem and progenitor cells from the quiescent G0state to GAlert. On exposure to tissue activating factors, cells in GAlertreadily enter G1to effect tissue repair. However, conversion of FR-HMGB1 to the disulfide form may result in deleterious inflammation through signaling via Toll-Like Receptors 2 (TLR-2) and 4 (TLR-4), and the Receptor for Advanced Glycation End products (RAGE). Using peptide arrays, biolayer interferometry and nuclear magnetic resonance, we mapped the residues and motifs of HMGB1 that interact with CXCL12, TLR-2, TLR-4, and RAGE. Identification of repeating sequences across the Box A and Box B domains that interact with CXCL12 enabled us to design a construct comprising two HMG B Boxes in tandem (dBB12L), which promotes tissue repair as effectively as wild type FR-HMGB1 but is unable to signal through TLR-2, TLR-4 or RAGE.
Uttroside B, a US-FDA-Designated Orphan Drug Against Hepatocellular Carcinoma (HCC), Impedes Non-alcoholic Steatohepatitis (NASH) and NASH -Induced HCC
Authors: Rayginia Tennyson P , Keerthana Chenicheri K. , Aiswarya Sreekumar U. , Shifana Sadiq C. , Jannet S , Varma Sanjay Suresh , Maria Joy P , Swetha Mundanattu , Retnakumary Archana Payickattu , Nath Lekshmi R. , Kalimuthu Kalishwaralal , Jaikumar Vishnu Sunil , Sundaram Sankar , Anto Nikhil Ponnoor , Isakov Noah , Harikumar Kuzhuvelil B. , Lankalapalli Ravi S. , Anto Ruby John 
Published: November 2024

AbstractIntroductionNon-alcoholic steatohepatitis (NASH) is characterized by excessive accumulation of fat, accompanied by inflammation and liver injury. NASH can lead to chronic conditions like fibrosis and cirrhosis, and has an elevated risk of progressing to hepatocellular carcinoma (HCC). Currently there are no FDA-approved drugs for the treatment of NASH.ObjectivesOur discovery of Uttroside B (Utt-B), a phytosaponin isolated fromSolanum nigrumLinn., which exhibits remarkable anti-HCC potential, has gained global recognition and is currently a US-FDA-designated ‘orphan drug’ against HCC. The present study highlights Utt-B as an anti-NASH molecule, by utilizing a High-Fat-Diet murine model, and as an inhibitor to the progression of NASH to HCC, using a streptozotocin-induced steatohepatitis-derived HCC animal model, thereby warranting its further validation as a propitious candidate drug molecule against NASH and NASH-induced HCC.MethodsHigh fat diet-induced NASH and streptozotocin-induced steatohepatitis-derived HCC were developed in C57BL/6 mice. Utt-B was administered intraperitoneally. q-PCR, immunoblotting and staining techniques such as Haematoxylin and eosin, Oil Red O, Sirius Red and Masson’s Trichrome, were performed to assess the therapeutic potency of Utt-B against NASH. Nanostring n-Counter analysis was conducted to verify the anti-fibrotic potential of Utt-B in NASH-induced HCC mouse model.ResultsUtt-B ameliorates the pathological features such as, steatosis, hepatocyte ballooning and inflammation associated with NASH. Utt-B up-regulates the expression of autophagy markers ATG7, Beclin-1 and LC-III and down-regulates the expression of α-SMA, the indicator protein for the activation of hepatic stellate cells. Utt-B hinders the development of fibrosis and halts the progression of NASH to HCC in NASH-induced HCC mouse model.ConclusionOur investigation reveals that Utt-B effectively alleviates NASH and abrogates its progression to HCC. As no treatment options are currently available against NASH, our findings are very relevant and strengthen the prospect of developing Utt-B as a potent drug for the treatment of NASH and NASH-induced HCC.Graphical Abstract