bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropathologically-directed profiling ofPRNPsomatic and germline variants in sporadic human prion disease
Authors: McDonough Gannon A. , Cheng Yuchen , Morillo Katherine , Doan Ryan N. , Kenny Connor J. , Foutz Aaron , Kim Chae , Cohen Mark L. , Appleby Brian S. , Walsh Christopher A. , Safar Jiri G. , Huang August Yue , Miller Michael B. 
Published: June 2024

AbstractCreutzfeldt-Jakob Disease (CJD), the most common human prion disease, is associated with pathologic misfolding of the prion protein (PrP), encoded by thePRNPgene. Of human prion disease cases, ∼1% were transmitted by misfolded PrP, ∼15% are inherited, and ∼85% are sporadic (sCJD). While familial cases are inherited through germline mutations inPRNP, the cause of sCJD is unknown. Somatic mutations have been hypothesized as a cause of sCJD, and recent studies have revealed that somatic mutations accumulate in neurons during aging. To investigate the hypothesis that somatic mutations inPRNPmay underlie sCJD, we performed deep DNA sequencing ofPRNPin 205 sCJD cases and 170 age-matched non-disease controls. We included 5 cases of Heidenhain variant sporadic CJD (H-sCJD), where visual symptomatology and neuropathology implicate focal initiation of prion formation, and examined multiple regions across the brain including in the affected occipital cortex. We employed Multiple Independent Primer PCR Sequencing (MIPP-Seq) with a median depth of >5,000X across thePRNPcoding region and analyzed for variants using MosaicHunter. An allele mixing experiment showed positive detection of variants in bulk DNA at a variant allele fraction (VAF) as low as 0.2%. We observed multiple polymorphic germline variants among individuals in our cohort. However, we did not identify bona fide somatic variants in sCJD, including across multiple affected regions in H-sCJD, nor in control individuals. Beyond our stringent variant-identification pipeline, we also analyzed VAFs from raw sequencing data, and observed no evidence of prion disease enrichment for the known germline pathogenic variants P102L, D178N, and E200K. The lack ofPRNPpathogenic somatic mutations in H-sCJD or the broader cohort of sCJD suggests that clonal somatic mutations may not play a major role in sporadic prion disease. With H-sCJD representing a focal presentation of neurodegeneration, this serves as a test of the potential role of clonal somatic mutations in genes known to cause familial neurodegeneration.
Dual roles of histone H3 lysine-4 in antagonizing Polycomb group function and promoting target gene expression
Authors: Anyetei-Anum Cyril S. , Leatham-Jensen Mary P. , Fox Geoffrey C. , Smith B. Rutledge , Krajewski Krzysztof , Strahl Brian D. , Dowen Jill M. , Matera A. Gregory , Duronio Robert J. , McKay Daniel J. 
Published: June 2024

AbstractTight control over cell identity gene expression is necessary for proper adult form and function. The opposing activities of Polycomb and trithorax complexes determine the ON/OFF state of targets like the Hox genes. Trithorax encodes a methyltransferase specific to histone H3 lysine-4 (H3K4). However, there is no direct evidence that H3K4 regulates Polycomb group target genesin vivo. Here, we demonstrate two key roles for replication-dependent histone H3.2K4 in target control. We find that H3.2K4 antagonizes Polycomb group catalytic activity and that it is required for proper target gene activation. We conclude that H3.2K4 directly regulates expression of Polycomb targets.
Polyommatine blue butterflies reveal unexpected integrity of the W sex chromosome amid extensive chromosome fragmentation
Authors: Hospodářská Monika , Chung Voleníková Anna , Koutecký Petr , Vila Roger , Talavera Gerard , Provazníková Irena , Dalíková Martina , Nguyen Petr 
Published: June 2024

AbstractChromosomal rearrangements are crucial in speciation, acting as barriers to gene flow. Holocentric chromosomes, such as those in Lepidoptera, can facilitate karyotype changes. Despite chromosome fusions being more common, speciation events are mostly linked to fissions. Notable karyotypic variation is observed in three clades of the subfamily Polyommatinae (Lycaenidae), with chromosome numbers ranging from n = 10 to n = 225. This study used flow cytometry and molecular cytogenetic analyses to investigate genome sizes and karyotypes in several species of the generaPolyommatusandLysandrawith derived and modal chromosome numbers. The findings show no support for polyploidy, supporting karyotypic diversification via fragmentation of chromosomes. Species with high chromosome numbers have larger genomes, which indicates a potential role of mobile elements but contradicts the hypothesis of holocentric drive. Telomeric signals were detected at the ends of fragmented chromosomes. No interstitial telomeric sequences were detected on autosomes. Interstitial telomeric signals on sex chromosomes, however, revealed multiple sex chromosome systems inPolyommatus dorylasandPolyommatus icarus, with two karyotype races differing in sex chromosome constitution in the latter. Pool-seq and coverage analyses indicated shared fusion of sex chromosomes with an autosome bearing the rDNA locus, followed by a fusion with chromosome 20 in the Czech population. Notably, the W chromosome resists fragmentation, likely due to epigenetic silencing protecting it from activity of mobile elements.
Matching Habitat Choice and the Evolution of a Species’ Range
Authors: Shirani Farshad , Miller Judith R. 
Published: June 2024

AbstractNatural selection is not the only mechanism that promotes adaptation of an organism to its environment. Another mechanism is matching habitat choice, in which individuals sense and disperse toward habitat best suited to their phenotype. This can in principle facilitate rapid adaptation, enhance range expansion, and promote genetic differentiation, reproductive isolation, and speciation. However, empirical evidence that confirms the evolution of matching habitat choice in nature is limited. Here we obtain theoretical evidence that phenotype-optimal dispersal, a particular form of matching habitat choice, is likely to evolve only in the presence of a steep environmental gradient. Such a gradient may be steeper than the gradient the majority of species typically experience in nature, adding to the collection of possible explanations for the scarcity of evidence for matching habitat choice. We draw this conclusion from numerical solutions of a system of deterministic partial differential equations for a population’s density along with the mean and variance of a fitness-related quantitative phenotypic trait such as body size. In steep gradients, we find that phenotype-optimal dispersal facilitates rapid adaptation on single-generation time scales, reduces within-population trait variation, increases range expansion speed, and enhances the chance of survival in rapidly changing environments. Moreover, it creates a directed gene flow that compensates for the maladaptive core-to-edge effects of random gene flow caused by random movements. These results suggest that adaptive gene flow to range margins, together with substantially reduced trait variation at central populations, may be hallmarks of phenotype-optimal dispersal in natural populations. Further, slowly-growing species under strong natural selection may particularly benefit from evolving phenotype-optimal dispersal.
The Naïve Bayes Classifier++ for Metagenomic Taxonomic Classification – Query Evaluation
Authors: Duan Haozhe (Neil) , Hearne Gavin , Polikar Robi , Rosen Gail 
Published: June 2024

AbstractThis study examines the query performance of the NBC++ (Incremental Naive Bayes Classifier) program for variations in canonicality, kmer size, databases, and input sample data size. NBC++ can successfully assess a wide range of superkingdoms using a small training database. We demonstrate that NBC++ and Kraken2 are affected by database depth with macro measures increasing with depth but that the full diversity of life, especially viruses, is still a challenge for these classifiers. NBC++ spends less time training but at the cost of long querying time. The major enhancements are to accommodate canonicalkmer storage (with major storage savings), adaptable and optimized memory allocation that quickens the query analysis and allows the classifier to be run on almost any system, and enables output of the log-likelihood values against each training genome which provides users with valualbe confidence information.
Cytokinin-inducibleDIRIGENT13involved in lignan synthesis and ROS accumulation promotes root growth and abiotic stress tolerance inArabidopsis
Authors: Melnikava Alesia , Perreau François , Paniagua Candelas , Cheng Sy-Chyi , Huang Li-Min , Ubogoeva Elena , Zemlyanskaya Elena , Yang Yu-Liang , Mouille Grégory , Arnaud Dominique , Hejatko Jan 
Published: June 2024

AbstractDirigent (DIR) proteins mediate regio- and stereoselectivity of phenoxy radical coupling of monolignols for (neo)lignan or lignin synthesis. However, the role of DIR proteins and lignans in plant development and response to environmental stresses remains elusive. Here, we provide a functional characterization of the cytokinin-responsiveDIRIGENT13(DIR13) inArabidopsis thaliana. DIR13 was localized to the root endodermis and at the margins of lateral root primordia and lateral roots. While not necessary for Casparian strip formation, DIR13 promoted both main and lateral root growth. Untargeted metabolomics and imaging mass spectrometry analyses unveiled the role of DIR13 in facilitating (neo)lignan synthesis in primary and lateral roots. Interestingly, DIR13 activated the production of putative oxomatairesinol and matairesinol-cysteine which are oxidative derivatives of the lignan matairesinol. Our data also identified DIR13 as an enhancer of salt and drought tolerance. Particularly,DIR13attenuated salt stress-mediated inhibition of germination and root growth. Moreover, DIR13 activated reactive oxygen species (ROS) accumulation both under control and salt stress conditions, and cytokinin further enhanced the salt-induced ROS production specifically in theDIR13overexpressing line. Our results uncover a role for DIR13-produced lignans in the priming of ROS accumulation, mediating both abiotic stress tolerance and the control of root architecture.
APax3lineage gives rise to transient haematopoietic progenitors
Authors: Canu Giovanni , Correra Rosamaria , Díez Pinel Guillermo , Castellan Raphaël F. P. , Denti Laura , Fantin Alessandro , Ruhrberg Christiana 
Published: June 2024

ABSTRACTDuring embryonic development, muscle tissues, skin, and a subset of vascular endothelial cells arise fromPax3-expressing embryonic progenitors defined as paraxial mesoderm. By contrast, haemogenic potential is well established for extra-embryonic mesoderm and intra-embryonic lateral plate mesoderm which do not expressPax3. To date, it is not known whether the haematopoietic system also containsPax3lineage cells. Here, we show that the mouse foetal liver and foetal circulation contain a transient population ofPax3lineage cells with hallmarks of haematopoietic progenitors and the potential to generate both myeloid and erythroid cells. We propose thatPax3lineage haematopoietic cells should be investigated to better understand normal haematopoietic development from different mesodermal derivatives. Further, genetic alterations ofPax3lineage haematopoietic cells should be investigated for their potential to cause haematopoietic malignancies.
Transient inhibition of type I interferon enhances CD8+T cell stemness and vaccine protection
Authors: Broomfield Benjamin J. , Tan Chin Wee , Qin Raymond Z. , Duckworth Brigette C. , Alvarado Carolina , Dalit Lennard , Chen Jinjin , Mackiewicz Liana , Muramatsu Hiromi , Pellegrini Marc , Rogers Kelly L. , Moon Woohyun J. , Nutt Stephen L. , Davis Melissa J. , Pardi Norbert , Wimmer Verena C. , Groom Joanna R. 
Published: June 2024

SUMMARYDeveloping vaccines that promote CD8+T cell memory is a challenge for infectious disease and cancer immunotherapy. TCF-1+stem cell-like memory T (TSCM) cells are important determinants of long-lived memory. Yet, the developmental requirements for TSCMformation are unclear. Here, we identify the temporal window for type I interferon (IFN-I) receptor (IFNAR) blockade to drive TSCMcell generation. TSCMcells were transcriptionally distinct and emerged from a transitional precursor of exhausted (TPEX) cellular state concomitant with viral clearance. TSCMdifferentiation correlated with T cell retention within the lymph node paracortex, due to increased CXCR3 chemokine abundance which disrupted gradient formation. These affects were due a counterintuitive increase in IFNψ, which controlled cell location. Combining IFNAR inhibition with mRNA-LNP vaccination promoted specific TSCMdifferentiation and enhanced protection against chronic infection. These finding propose a new approach to vaccine design whereby modulation of inflammation promotes memory formation and function.HIGHLIGHTSEarly, transient inhibition of the type I interferon (IFN) receptor (IFNAR) during acute viral infection promotes stem cell-like memory T (TSCM) cell differentiation without establishing chronic infection.TSCMand precursor of exhausted (TPEX) cellular states are distinguished transcriptionally and by cell surface markers.Developmentally, TSCMcell differentiation occurs via a transition from a TPEXstate coinciding with viral clearance.Transient IFNAR blockade increases IFNψ production to modulate the ligands of CXCR3 and couple TSCMdifferentiation to cell retention within the T cell paracortex of the lymph node.Specific promotion of TSCMcell differentiation with nucleoside-modified mRNA-LNP vaccination elicits enhanced protection against chronic viral challenge.
Identification of a mimotope of a complex gp41 Human Immunodeficiency VIrus epitope related to a non-structural protein ofHepaciviruspreviously implicated in Kawasaki disease
Authors: Sojar Hakimuddin , Baron Sarah , Hicar Mark D 
Published: June 2024

AbstractBackgroundWe have previously isolated a highly mutated VH1-02 antibody termed group C 76-Q13-6F5 (6F5) that targets a conformational epitope on gp41. 6F5 has the capacity to mediate Ab dependent cell cytotoxicity (ADCC). When the VH1-02 group C 76 antibodies variable chain sequence was reverted to germline (76Canc), this still retained ADCC activity. Due to this ability for the 76Canc germline antibody to functionally target this epitope, we sought to identify a protein target for vaccine development.MethodsInitially, we interrogated peptide targeting by screening a microarray containing 29,127 linear peptides. Western blot and ELISAs were used to confirm binding and explore human serum targeting. Autoimmune targeting was further interrogated on a yeast-displayed human protein microarray.Results76Canc specifically recognized a number of acidic peptides. Meme analysis identified a peptide sequence similar to a non-structural protein ofHepaciviruspreviously implicated in Kawasaki disease (KD). Binding was confirmed to top peptides, including theHepacivirus-related and KD-related peptide. On serum competitions studies using samples from children with KD compared to controls, targeting of this epitope showed no specific correlation to having KD. Human protein autoantigen screening was also reassuring.ConclusionsThis study identifies a peptide that can mimic the gp41 epitope targeted by 76C group antibodies (i.e.a mimotope). We show little risk of autoimmune targeting including any inflammation similar to KD, implying non-specific targeting of this peptide during KD. Development of such peptides as the basis for vaccination should proceed cautiously.
Farmed crickets raised with dermestids suffer from reduced and delayed growth, but not enough to explain reports of dramatic yield loss
Authors: Muzzatti MJ , Ritchie MW , Bess EC , Bertram SM , MacMillan HA 
Published: June 2024

AbstractThe mass production of crickets for food and feed is an expanding North American industry. Facilities that mass rear insects are at risk of pest infestations because the optimal environmental conditions for rearing beneficial species may also support the development of pest species. Here, we present the first recorded results detailing the interactions between dermestids and farmed crickets. Cricket farms have reported extremely low harvest yield during heavy dermestid infestations, but the exact reasons for this low yield are unknown. Many dermestid larvae are covered in dense, detachable, barbed setae called hastisetae, which are used by the larvae as an active trapping system against arthropod predators. We designed a series of experiments to test the hypotheses that dermestids (Dermestes aterDeGeer) may be directly impacting cricket (Gryllodes sigillatusWalker) yield through the physical effects of hastisetae ingestion and/or indirectly impacting cricket yield through competition for fishmeal, a primary source of protein in conventional cricket feed. Our predictions that cricket life history and survival would be negatively affected by dermestids were largely refuted. Females fed infested diets grew less mass, but not smaller body size, compared to females fed uninfested diets. We also found that while crickets experienced delayed growth early in life after living with dermestids, they were able to tolerate living with, and consuming, dermestid larvae. We discuss how these findings have led to new hypotheses concerning how dermestid infestations drive reductions in cricket farm yield.
Sublethal insecticide exposure of larvae affects the blood-feeding behaviour of adult mosquitoes
Authors: Zeferino Tiago G. , Acerbi Gwendoline , Koella Jacob C. 
Published: June 2024

AbstractBecause of their widespread use for the control of disease vectors and agricultural pests, insecticides have become ubiquitous in the environment, including in water bodies harbouring mosquito larvae. These are therefore continuously exposed to sublethal doses. Since this has long-lasting effects on the mosquitoes’ physiology and life-history, we expected that it may also affect behaviours that underlie the mosquitoes’ population dynamics and disease epidemiology, such as egg-laying preference, blood-feeding motivation, and host-seeking behaviour. Using an insecticide-sensitive and a resistant strain ofAnopheles gambiae, an important malaria vector, we evaluated the effects of sublethal exposure to permethrin throughout larval development on the resistance to the insecticide in adults, on host-seeking behaviour, on the motivation to blood-feed, and on egg-laying behaviour. Resistance, assessed by rates of knock-down and mortality, were similar between exposed and unexposed mosquitoes. However, exposure to sublethal doses of insecticide caused female mosquitoes to split their egg clutches into two parts and increased the motivation of mosquitoes to seek blood meals through permethrin-treated nets, regardless of their sensitivity to the insecticide. Furthermore, it enhanced the natural preference of resistant strains for permethrin-treated nets and increased their blood-meal size. Our results thus suggest that sublethal insecticide concentrations in larval breeding sites have important epidemiological implications.
Susceptibility Patterns of Multiple Antibiotic-Resistant Bacteria from Wound and Urine Samples to the Extract ofSpondias Mombin(Linn)
Authors: Okiti AF , Oladunmoye MK , Ogundare AO 
Published: June 2024

ABSTRACTThis study evaluates the antibacterial activity ofSpondias mombinL. against multiple antibiotic-resistant bacteria isolated from wound and urine samples of patients attending five (5) selected hospitals in Akure, Ondo State, Nigeria. A total of 313 bacterial isolates were isolated from 353 samples of wound and urine using standard bacteriological procedures, withPseudomonas aeruginosaandStaphylococcus aureusbeing the most predominant in urine and wound samples, respectively. The methanolic extract ofS. mombinwas the most effective against wound isolates, while the aqueous extract was the most effective against urine isolates. The results showed that the methanol extract ofS. mombinhad a zone of inhibition of 24.00±0.00, 30.67±0.33 and 19.33±0.33 mm respectively, againstS. aureus, S. epidermidisandP. aeruginosaat 100 mg/ml. The aqueous extract had a zone of inhibition of 24.67±0.33, 27.33±0.33, 18.67±0.33, 24.67±0.33, 23.67±0.33, 21.33±0.33 and 21.67±0.33 mm againstEscherichia coli, Klebsiella pneumoniae, P. aeruginosa, Proteus mirabilis, S. aureus, S. saprophyticusandTrichomonas vaginalisrespectively, at 100 mg/ml. The phytochemical constituents of the extracts include alkaloids, anthraquinones, cardiac glycosides, flavonoids, phenols, saponins, steroids and tannins. These compounds may be responsible for the antibacterial activity ofS. mombinagainst the multiple antibiotic-resistant bacterial isolates. The findings of this study demonstrates the potential ofS. mombinas an alternative treatment for multiple antibiotic-resistant bacteria from wound and urine.
Candida albicansenhanceStaphylococcus aureusvirulence by progressive generation of new phenotypes
Authors: Arévalo-Jaimes Betsy Verónica , Torrents Eduard 
Published: June 2024

AbstractCandida albicansandStaphylococcus aureushave been co-isolated from several biofilm- associated diseases, including those related to medical devices. This association confers advantages to both microorganisms, resulting in detrimental effects on the host. To elucidate this phenomenon, the present study investigated colony changes derived from non-physical interactions betweenC. albicansandS. aureus. We performed proximity assays by confronting colonies of the yeast and the bacteria on agar plates at six different distances for 9 days. We found that colony variants ofS. aureusoriginated progressively after prolonged exposure toC. albicansproximity, specifically in response to pH neutralization of the media by the fungi. The new phenotypes ofS. aureuswere more virulent in aGalleria mellonellalarvae model compared to colonies grown withoutC. albicansinfluence. This event was associated with an upregulation ofRNAIIIandAgrAexpression, suggesting a role for α-toxin. Our findings indicate thatC. albicansenhancesS. aureusvirulence by inducing the formation of more aggressive colonies.ImportanceFor decades, it has been known thatC. albicansincreaseS. aureusvirulence, resulting in a “lethal synergism”. However, it was only recently identified that this outcome is driven by the sustained activation of the staphylococcalagrsystem in response toC. albicansenvironmental modifications. Our experimental design allowed us to observe individual changes over time caused by the proximity of both microorganisms. As a result, we report for first time thatC. albicansexposure induces the generation and favors the growth ofS. aureuscolony variants with increased expression of virulence factors. Our findings highlight the importance to understanding the intricate connection between environmental responses, virulence and fitness inS. aureuspathogenesis.