bluuebunny/crossref_metadata_2025_split huggingface dataset:
Four chromosomally clustered class-C β-lactamases (blaAmpH1/2/3/4) control the cephalosporin hydrolysis inMycobacterium tuberculosisand similar genetic loci appeared as pseudogenes inMycobacterium leprae
Authors: Chakraborty Asit Kumar 
Published: September 2023

SummaryMycobacterium tuberculosis(Mt) chromosomal ten PBPs and one class-A β-lactamase (blaC) were implicated in multi-drug resistance against penicillin, cephalosporin and carbapenem drugs. TheE. coliClass-A PBP1A and PBP1B proteins referred as PonA1 and PonA2 inMtwith 34% homologies whereas Class-B PBP2 referred as PbpA and PbpB sub-class proteins with 27% homologies. The class-C PBPs were, PBP4, MecA_N, DacB1, DacB2 and AmpH1- AmpH4. During database search, we found that manyMtPbp4 had no homology toE. coliPBP4 and such enzyme were found to be AmpH class with AmpC, ACC, DHA and GES β- lactamases similarities although one of such enzymes suggested as AmpH but the other referred as DacB or PBP5 in the literature. We investigated theMtwhole genomes (accession nos. AL123456, CP001642, CP054013, CP001641, CP025597) to get authentic PBP4 inMtstrain FDAARGOS_757 genome (protein id. AUP69687, 34% homology toE. coliPBP4) which was designated as conserved protein in chromosomes ofMtstrains H37Rv, H37Rv-1, GG-36-11 and CCDC5180 making confusion in data analysis. Similarly, we BLASTP homology searched with plasmid-mediated 24 β-lactamases suggested that fourblaAmpH genes, (AmpH1, AmpH2, AmpH3andAmpH4) predominantly control the degradation of cephalosporins inM. tuberculosisbut such genes were found as pseudogenes inM. leprae. TheMtAmpH1/2/3/4 enzymes had better homologies withV. parahaemolyticusandYersinia pekkaneniiAmpH enzyme as well as withE. coliAmpH enzyme. The DacB1 (PBP6) and DacB2 (PBP7) enzymes had blaTEM similarity but no AmpH similarity indicating blaC and DacB1/B2 controlled the Penicillin hydrolysis inMt. The blaC enzyme had 30% homology toS. aureusblaZ β-lactamase but such enzyme was also missing inM. leprae. Homology search suggested that carbapenem hydrolysis by blaOXA-23/51-like PBPA/B enzymes and blaOXA-58 related MecA_N domain β-lactamase which has 21% similarity toS. aureusmecA enzyme. The PonA1/A2 had no homology to 24 classes of β-lactamases but still were popular enzymes implicated for better penicillin hydrolysis. We designed primers forMtPBPs to check transcription of individual genes by RT-PCR as well as to check chromosomal locus by BLASTN search after WGS. TheE. coligenome had no similarities toblaAmpH1/2/3/4 genes but a 17nt (5’- CCTTGGTGCCGTCGACC-3’) sequence found in pKEC-a3c plasmid ofC. fruendiiwith homology toblaAmpH4 gene (nt. 1236-1252) and shared a homology with IS1182-like ISKpn6 transposase of plasmids. The oligonucleotides selected manyMtchromosomes and located conserved blaAmpH4 protein in all cases. However, D435E and F495V mutations in theMtstrain 5521 blaAmpH4 were evident and frameshift deletions located inMtstain FDAARGOS_756blaAmpH4 gene with no protein was made. Thus, mutations, deletions and rearrangements mediated by IS-elements were the driving force to make newAmpHgenes inM. tuberculosis.
Influenza A virus H1N1-derived circNP37 positively regulates viral replication by sponging host miR-361-5p
Authors: Zhu Chunyu , Wang Jingyu , Du Yalan , Li Chunli , Hao Mengchan , Zhang Yu , Zhang Xiaoqing , Guan Yiwei , Zheng Fangliang , Zhang Yuan , Chen Jianjun 
Published: September 2023

SummaryRNA viruses, such as respiratory syncytial virus and SARS-CoV-2, can generate viral circular RNAs (circRNAs), which may play important roles during viral infection. However, whether influenza A viruses have this ability to generate viral circRNAs remains unknown. In this study, we discovered that the negative-strand RNA of the H1N1 nucleoprotein (NP) gene can generate a circRNA, designated circNP37. Furthermore, we demonstrated that circNP37 positively regulated viral replication by competitively sponging host miR-361-5p which inhibited polymerase basic protein 2 (PB2) expression. These results were confirmed using in vivo experiments. Compared with wild-type virus, infection with circNP37 knockout virus resulted in a reduced viral load in the lungs. This study demonstrates, for the first time, the existence and biological function of H1N1-derived circNP37. These findings help us better understand the mechanisms of influenza virus replication and pathogenicity.HighlightsNegative-strand RNA of the H1N1 nucleoprotein gene can generate a circRNACircNP37 plays important roles in viral replication and viral-host interactionsCircNP37 positively regulates replication by competitively sponging host miR-361-5peTOC BlurbIn this study, we found that influenza A virus H1N1 infection can generate virus-derived circRNA, circNP37. We also demonstrated that circNP37 positively regulate viral PB2 gene expression and viral replication via sponge host miR-361-5p during viral infection.
The impact of chemical pollution across major life transitions: a meta-analysis on oxidative stress in amphibians
Authors: Martin Colette , Capilla-Lasheras Pablo , Monaghan Pat , Burraco Pablo 
Published: September 2023

AbstractAmong human actions threatening biodiversity, the release of anthropogenic chemical pollutants -which have become ubiquitous in the environment- is a major concern. Chemical pollution can induce oxidative stress and damage by causing the overproduction of reactive oxygen species (ROS), and affecting the antioxidant system. In species undergoing metamorphosis (∼80% of all extant animal species), antioxidant responses to chemical pollution may differ between pre- and post-metamorphic stages. Here, we meta-analysed (N = 86 studies, k = 2,012 estimates) the impact of chemical pollution on the redox balance across the three major amphibian life stages (embryo, larva, adult). Before metamorphosis, embryos and larvae activate their antioxidant pathways and do not show increased oxidative damage. In contrast, post-metamorphic individuals show unnoticeable antioxidant responses, and a marked oxidative damage in lipids. Also, type of pollutant (i.e., organic vs inorganic) promotes contrasting effects across amphibian life stages. Our findings show a divergent evolution of the redox balance in response to pollutants across life transitions of metamorphosing amphibians, likely linked to the characteristics of each life stage. Further comparative mechanistic approaches to wildlife responses to global changes will improve our understanding of these eco-evo-devo processes.
A new T Cell Receptor in Squamata Reptiles
Authors: Gambón-Deza Francisco 
Published: September 2023

AbstractSquamata exhibit a loss of genes for the gamma/delta T-lymphocyte receptor chains and a significant decrease in the number of V genes at the TRBV locus. Through genome analysis, I have discovered a new locus that contains V, J, C, and TM genes that have a similar structure to the classical TCR chains. This gene is viable, as demonstrated by the presence of messenger RNAs in the transcriptomes. Analyses using the AlphaFold2 program indicate that the deduced protein chain is associated with the alpha chain of the TCR. I have named this new chain “epsilon,” and it forms a new TCR alpha/epsilon. Evolutionarily, the epsilon chain arose from a duplication of the beta chain gene at the time of the divergence of amphibians and reptiles and has since been specifically maintained in Squamata.
Schizosaccharomyces versatilisrepresents a distinct evolutionary lineage
Authors: Etherington Graham J , Gil Elisa Gomez , Haerty Wilfried , Oliferenko Snezhana , Nieduszynski Conrad A. 
Published: September 2023

AbstractThe fission yeast speciesSchizosaccharomyces japonicusis currently divided into two varieties –S. japonicusvar.japonicusandS. japonicusvar.versatilis. Here we examine the var.versatilisisolate CBS5679. The CBS5679 genome shows 88% coding sequence identity to the reference genome ofS. japonicusvar.japonicusat the coding sequence level, with phylogenetic analyses suggesting that it has split from theS. japonicuslineage 25 million years ago. The CBS5679 genome contains a reciprocal translocation between chromosomes 1 and 2, together with several large inversions. The products of genes linked to the major translocation are associated with “metabolism” and “cellular assembly” ontology terms. We further show that CBS5679 does not generate viable progeny with the reference strain ofS. japonicus. Although CBS5679 shares closer similarity to the “type” strain of var.versatilisas compared to S.japonicus, it is not identical to the type strain, suggesting population structure within var.versatilis. We recommend that the taxonomic status ofS. japonicusvar.versatilisis raised, with it being treated as a separate species,Schizosaccharomyces versatilis.Take-awayThe taxonomic status ofSchizosaccharomyces versatilisis addressed.S. versatilisdiverged fromS. japonicusaround 25 million years ago.S. versatilisdoes not produce viable progeny in crosses withS. japonicus.S. versatilishas a reciprocal translocation between chromosomes 1 and 2.The Gene Ontology terms for genes in the translocations are enriched for terms connected to “metabolism” and “cellular assembly”.
Difference in Differences analysis evaluates the effects of the Badger Control Policy on Bovine Tuberculosis in England
Authors: Birch Colin P.D. , Bakrania Mayur , Prosser Alison , Brown Dan , Withenshaw Susan M. , Downs Sara H. 
Published: September 2023

AbstractPersistent tuberculosis (TB) in cattle populations in England has been associated with an exchange of infection with badgers(Meles meles). A badger control policy (BCP) commenced in 2013. Its aim was to decrease TB in cattle by reducing the badger population available to provide a wildlife reservoir for bovine TB. Monitoring data from 52 BCP intervention areas 200-1600 km2in size, starting over several years, were used to estimate the change in TB incidence rate in cattle herds, which was associated with time since the start of the BCP in each area. A Difference in Differences analysis addressed the non-random selection and starting sequence of the areas. Herd incidence rate of TB reduced by 56% (95% Confidence Interval 43-67%) up to the fourth year of BCP interventions, with the largest reductions in the second and third years. There was insufficient evidence to judge whether incidence rate reduced further beyond four years. These estimates are the most precise for the timing of decline in cattle TB associated with interventions primarily targeting badgers. They are within the range of previous estimates from England and Ireland. This analysis indicates the importance of reducing transmission from badgers to reduce the incidence of TB in cattle, noting that vaccination of badgers, fertility control and on farm biosecurity may also achieve this effect.
Telomere-to-telomereSchizosaccharomyces japonicusgenome assembly reveals hitherto unknown genome features
Authors: Etherington Graham J , Wu Pei-Shang , Oliferenko Snezhana , Uhlmann Frank , Nieduszynski Conrad A. 
Published: September 2023

AbstractSchizosaccharomyces japonicusbelongs to the single-genus class Schizosaccharomycetes, otherwise known as ‘fission yeasts’. As part of a composite model system with its widely studiedS. pombesister species,S. japonicushas provided critical insights into the workings and the evolution of cell biological mechanisms. Furthermore, its divergent biology makesS. japonicusa valuable model organism in its own right. However, the currently available short-read genome assembly contains gaps and has been unable to resolve centromeres and other repeat-rich chromosomal regions. Here we present a telomere-to-telomere long-read genome assembly of theS japonicusgenome. This includes the three megabase-length chromosomes, with centromeres hundreds of kilobases long, rich in 5S ribosomal RNAs, transfer RNAs, long terminal repeats, and short repeats. We identify a gene-sparse region on chromosome 2 that resembles a 331 kb centromeric duplication. We revise the genome size ofS. japonicusto at least 16.6 Mb and possibly up to 18.12 Mb, at least 30% larger than previous estimates. Our whole genome assembly will support the growingS. japonicusresearch community and facilitate research in new directions, including centromere and DNA repeat evolution, and yeast comparative genomics.Take-awayA telomere-to-telomere genome assembly of the fission yeastS. japonicusChromosome 2 harbours a previously unknown second centromere-like regionThe estimated genome size ofS. japonicusmay be up to 18.12 Mb
Suppressor of Cytokine Signaling 3 Derived Peptide as a Therapeutic for Inflammatory, and Oxidative Stress Induced Damage to the Retina
Authors: Ahmed Chulbul M. , Patel Anil P. , Johnson Howard M. , Ildefonso Cristhian J. , Lewin Alfred S. 
Published: September 2023

AbstractPurposeInflammation and oxidative stress are contributing factors to age-related macular degeneration (AMD) and other retinal diseases. We tested a cell penetrating peptide from the kinase inhibitory region of intracellular checkpoint inhibitor Suppressor of Cytokine Signaling 3 (R9-SOCS3-KIR) peptide for its ability to blunt the inflammatory or oxidative pathways leading to AMD.MethodsWe used Anaphylatoxin C5a to mimic the effect of activated complement, lipopolysaccharide (LPS) and TNFα to stimulate inflammation, and paraquat to induce mitochondrial oxidative stress. We used a human RPE cell line (ARPE-19) as proliferating cells and a mouse macrophage cell line (J774A.1) to follow cell propagation by microscopy or cell titer assays. We evaluated inflammatory pathways by monitoring nuclear translocation of NF-κB p65 and MAP kinase p38, and we used qRT-PCR and Western blots to evaluate induction of inflammatory markers. In differentiated ARPE-19 monolayers, we evaluated the integrity of tight junction proteins by microscopy and measurement of transepithelial electrical resistance. We used intraperitoneal injection of sodium iodate to test the ability of R9-SOC3-KIR to prevent RPE and retinal injury as assessed by fundoscopy, Optical Coherence Tomography (OCT) and histology.ResultsR9-SOCS3-KIR treatment suppressed C5a-induced nuclear translocation of the NF-kB activation domain p65 in undifferentiated ARPE-19 cells. TNF-mediated damage to tight junction proteins in RPE and the loss of transepithelial electrical resistance were prevented in the presence of R9-SOCS3-KIR. R9-SOCS3-KIR prevented the increased expression of genes related to inflammation in response to C5a treatment. R9-SOCS3-KIR also blocked lipopolysaccharide (LPS) induction of cyclooxygenase and inflammatory markers including IL-6, MCP1, COX-1 and IL-1β. R9-SOCS3-KIR prevented paraquat mediated cell death and enhanced the levels of antioxidant effectors. Daily eye drop instillation of R9-SOCS3-KIR protected against retinal injury caused by i.p. administration of sodium iodate.ConclusionR9-SOCS3-KIR blocks the induction of inflammatory signaling in cell culture and reduces retinal damage in a widely used model of RPE/retina oxidative injury. Since this peptide can be administered by corneal instillation, this treatment may offer a convenient way to slow the progression of ocular diseases arising from inflammation and chronic oxidative stress.
CATHI: An interactive platform for comparative genomics and homolog identification
Authors: Becker Lukas , Spohr Philipp , Klau Gunnar W. , Axmann Ilka M. , Fraune Sebastian , Schmelling Nicolas M. 
Published: September 2023

AbstractBioinformatics has established itself as a central pillar of modern biology. Specifically, comparative genomics enables scientists to study a vast number of genomes efficiently. These comparative analyses shed light on the evolution and potential function of genomes and genes, but are also increasingly used as a key tool for metabolic engineering and synthetic biology by identifying appropriate targets for modification. While numerous sophisticated tools for comparative genomics and homolog identification exist, those tools predominantly target highly skilled bioinformatics users. Consequently, many biologists either defer such analyses to their more versed bioinformatic collaborators or resort to suboptimal tools. Here, we present an intuitive solution available on all major operating systems, easily accessed through common web browsers. CATHI – Comparative Analysis Tool for Homolog Identification – integrates a suite of best-practice bioinformatic tools, encompassing BLAST for homology searches, MAFFT for multiple sequence alignment, FastTree2 for phylogeny reconstruction, and clinker for synteny analysis. Specifically tailored to biologists, CATHI orchestrates predefined settings and automated pipelines, obviating the need for programming expertise. This platform empowers researchers to confidently engage in detailed comparative genomics studies by streamlining the analytical process. The interactive framework provides users with a plethora of options. This includes real-time execution and progress monitoring, facilitates dynamic result tracking, and a set of search functions across NCBI databases like CDD or ProtFam. Users can interactively engage in data exploration, filtering, and visualization through CATHI’s intuitive interface. Furthermore, the seamless export of project data in standard formats (FASTA, Newick, CSV, and HTML) facilitates the integration with further third-party tools such as TreeViewer and Jalview. To benchmark CATHI, we revisited the comparative analysis of cyanobacterial circadian clock proteins conducted by Schmelling et al. in 2017, revealing consistent global patterns among identified homologs, while also highlighting individual variations attributed to the expansion of available databases.
Discovery of Natural Bispecific Antibodies: Is Psoriasis Induced by a ToxigenicCorynebacterium simulansand Maintained by CIDAMPs as Autoantigens?
Authors: Schröder Jens-Michael 
Published: September 2023

AbstractThe high abundance ofCorynebacterium simulansin psoriasis skin suggests a contribution to the psoriasis etiology via cell envelope components, which may cause skin inflammation and immune responses. This hypothesis was tested in an exploratory study, where Western Blot (WB) analyses with extracts of heat-treatedC. simulansand psoriasis serum-derived IgG exhibited a single 16 kDa- WB-band. Proteomic analyses revealed, among others, ribosomal proteins as candidateC. s.-antigens. A peptidomic analysis unexpectedly showed that psoriasis-serum-derived IgG already contained 31 immunopeptides originating fromCorynebacteria ssp., suggesting the presence of natural bispecific antibodies (BsAbs). Moreover, peptidomic analyses revealed 372 “DECOY”-peptides with similarity to virus- and phage proteins, includingCorynebacterium diphtheriae phage, and similarity to diphtheria toxin. Strikingly, upon a peptidomic analysis for peptides of human origin, 64 epitopes of major psoriasis autoantigens were identified, which originated from the spacer region of filaggrin, from hornerin repeats, SPINK9, keratin 9, caspase 14, desmoplakin, suprabasin, keratin 2, keratin1, keratin 6C, apolipoprotein A1, a Selene-binding protein, H1.8 linker histone, and the transcription factor BCLAF3. Most identified antigens represent potential “Cationic Intrinsically Disordered Antimicrobial Peptides (CIDAMPs)”, which are generated within the fully differentiated epidermis. These may form complexes with bacterial disordered protein regions, representing chimeric antigens containing discontinuous epitopes. In addition, among 128 low-abundance immunopeptides, 48 are putatively psoriasis-relevant such as epitopes of IL-12, and the receptors of PGE2, vitamin D3, and IL-10. Further, 47 immunopeptides originated from tumor antigens such as CT47A, SDCCAG3, BRCA2, MAGEA6, RNASE4, and the endogenous retrovirus HERV-K. I propose that persistent infection with a toxigenicC. simulansinitiates psoriasis, which is exacerbated as an autoimmune disease by CIDAMPs as autoantigens. The discovery of natural BsAbs allows the identification of antigen epitopes from microbes, viruses, autoantigens, and tumor-antigens, and may help to develop epitope- specific peptide-vaccines and therapeutic approaches with antigen-specific regulatory T cells to improve immune tolerance in an autoimmune disease-specific-manner.
DropBlot: single-cell western blotting of chemically fixed cancer cells
Authors: Liu Yang , Herr Amy E. 
Published: September 2023

AbstractTo further realize proteomics of archived tissues for translational research, we introduce a hybrid microfluidic platform for high-specificity, high-sensitivity protein detection from individual chemically fixed cells. To streamline processing-to-analysis workflows and minimize signal loss, DropBlot serially integrates sample preparation using droplet-based antigen retrieval from single fixed cells with unified analysis-on-a-chip comprising microwell-based antigen extraction followed by chip-based single-cell western blotting. A water-in-oil droplet formulation proves robust to the harsh chemical (SDS, 6M urea) and thermal conditions (98°C, 1-2 hr.) required for sufficient antigen retrieval, and the electromechanical conditions required for electrotransfer of retrieved antigen from microwell-encapsulated droplets to single-cell electrophoresis. Protein-target retrieval was demonstrated for unfixed, paraformaldehyde-(PFA), and methanol-fixed cells. We observed higher protein electrophoresis separation resolution from PFA-fixed cells with sufficient immunoreactivity confirmed for key targets (HER2, GAPDH, EpCAM, Vimentin) from both fixation chemistries. Multiple forms of EpCAM and Vimentin were detected, a hallmark strength of western-blot analysis. DropBlot of PFA-fixed human-derived breast tumor specimens (n = 5) showed antigen retrieval from cells archived frozen for 6 yrs. DropBlot could provide a precision integrated workflow for single-cell resolution protein-biomarker mining of precious biospecimen repositories.
Clusters of multiple long-term conditions in three UK datasets: a latent class analysis
Authors: Steell Lewis , Krauth Stefanie J. , Ahmed Sayem , Dibben Grace , McIntosh Emma , Hanlon Peter , Lewsey Jim , Nicholl Barbara I. , McAllister David , Taylor Rod S. , Singh Sally J. , Mair Frances S. , Jani Bhautesh D. 
Published: September 2023

AbstractIntroductionLatent class analysis (LCA) can be used to identify subgroups within populations based on unobserved variables. LCA can be used to explore whether certain long-term conditions (LTC) occur together more frequently than others in patients with multiple-long term conditions. In this manuscript we present findings from applying LCA in three large-scale UK databanks.MethodsWe applied LCA to three different UK databanks: Secure Anonymised Information Linkage databank [SAIL], UK Biobank, and Understanding Society: the UK Household Longitudinal Study [UKHLS] and four different age groups: 18-36, 37-54, 55-73, and 74+ years. The optimal number of classes in each LCA was determined using maximum likelihood. Sample size adjusted Bayesian Information Criterion (aBIC) was used to assess model fit and elbow plots and model entropy were used to assess the best number of latent classes in each model.ResultsBetween three to six clusters were identified in the different datasets and age groups. Although different in detail, similar types of clusters were identified between datasets and age groups which combine disorders around similar systems incl. Cardiometabolic clusters, Pulmonary clusters, Mental health clusters, Painful conditions clusters, and cancer clusters.