bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global evolutionary patterns ofYersinia pestisand its spread into Africa
Authors: Mas Fiol Guillem , Lemoine Frédéric , Mornico Damien , Bouvier Guillaume , Andrades Valtueña Aida , Duchene Sebastian , Campagne Pascal , Balière Charlotte , Kwasiborski Aurélia , Caro Valérie , Beau Rémi , Savin Cyril , Céspedes Manuel , Rajerison Minoarisoa , Shako Jean-Christophe , Carniel Elisabeth , Slavin Philip , Rascovan Nicolás , Pizarro-Cerdá Javier 
Published: November 2024

AbstractThe zoonotic pathogenYersinia pestis, the etiologic agent of plague, has caused three major pandemics and diversified in different lineages currently established in endemic areas worldwide1–3. However, some regions like continental Africa have been poorly covered within the global diversity and epidemiological history of this pathogen2,4–6. Here, we report the whole-genome sequences of 1,124Y. pestisisolates collected from endemic areas worldwide over 116 years, nearly doubling the available genomic data for the species. By integrating population genomics and historical research, we retrace the introduction of multipleY. pestislineages into continental Africa, revealing the diversity of the 1.ANT lineage, its historical emergence and its spread to and within Africa since the late 17th century. We identify key mechanisms of genome evolution, including signatures of adaptive evolution present in virulence and biofilm-related genes such as RovA, a master virulence regulator, which likely play a role in the pathogen’s adaptation and endemic persistence. Additionally, our findings reveal an increased trajectory of genome degradation and expansion of IS elements in different lineages. This trend appears especially pronounced in 1.ANT genomes, promoting the remarkable genomic variation within this lineage. Taken together, our findings shed light on the introduction and evolutionary history of plague in Africa and provide a comprehensive framework for understanding the global diversity and genome evolution ofY. pestis, revealing potential factors contributing to its long-term adaptation in endemic areas.
A “non-muscle” α-actinin is an intrinsic component of the cardiac Z-disc and regulates sarcomere turnover, contractility, and heart remodeling
Authors: Hayes James B , Ritter Dylan , Neininger-Castro Abigail C , Willet Alaina H , Caplan Leah R , Wang Yu , Liu Xiao , Taneja Nilay , Sanchez Zachary C , Smart Kyra , Reinhart-King Cynthia A , Liu Qi , Tyska Matthew J , Tabdanov Erdem D , Wells Quinn S , Knapik Ela W , Burnette Dylan T 
Published: November 2024

ABSTRACTCardiac sarcomeres generate the fundamental forces behind each heartbeat and are thought to contain only muscle-specific cytoskeletal proteins. We show that a widely expressed actin cross-linking protein, α-actinin 4 (ACTN4), is a sarcomere component of the human and zebrafish heartin vivoand in human iPSC-derived cardiac myocytes (CMs)in vitro. A confluence of biochemical experiments, immunofluorescence, and AI modeling suggest ACTN4 forms a heterodimeric complex with muscle-specific ACTN2 at the cardiac Z-disc, the cardiac sarcomere border. ACTN4 depletion from human iPSC-CMs stabilizes canonical sarcomere proteins and drives contractility-dependent cellular hypertrophy while ACTN4 overexpression destabilizes sarcomeres. ACTN4 depletion from zebrafish embryos specifically increases ventricular contractility which drives atrial enlargement, suggesting biomechanically driven atrial remodeling. ACTN4-associated phenotypes in both model systems lack hallmarks of cardiac disease models and an ACTN4 variant in humans is associated with reduced risk for disease. Our findings suggest a “non-muscle” actinin regulates heart contractility and influences clinical outcomes related to heart failure.
Actin filament assembly driven by distributive polymerases clustered on membrane surfaces
Authors: Mullins R. Dyche , Skruber Kristen 
Published: November 2024

ABSTRACTActin filaments created by the Arp2/3 complex form branched networks, that grow and push against cellular membranes. We employ theory and simulation to describe how membrane surfaces accelerate filament assembly via clustering of proteins that bind actin monomers and/or profilin-actin complexes. Briefly, thermal fluctuations drive filament tips on constrained, two-dimensional random walks across the membrane, where they encounter multiple actin-charged polymerases. At low actin concentrations, filament elongation is limited by delivery of monomers to the membrane surface; at high actin concentrations, elongation depends on how quickly fluctuating filaments search the membrane. Surface-mediated polymerization can outpace solution-mediated elongation, even at high actin concentrations (>200 µM). The finite time required for profilin dissociation decreases the advantage conferred by surface-associated polymerases, but only in the absence of force. Load forces enhance the effect of surface polymerases, which can both accelerate elongation and increase the force required to stall filament assembly.
Cavin1 binding nanobodies reveal structural flexibility and regulated interactions of the N-terminal coiled-coil domain
Authors: Gao Ya , Tillu Vikas A. , Wu Yeping , Rae James , Hall Thomas E. , Chen Kai-en , Weeratunga Saroja , Guo Qian , Livingstone Emma , Tham Wai-Hong , Parton Robert G. , Collins Brett M. 
Published: November 2024

ABSTRACTCaveolae are abundant plasma membrane structures that regulate signalling, membrane homeostasis, and mechanoprotection. Their formation is driven by caveolins and cavins and their coordinated interactions with lipids. We have developed nanobodies against the trimeric HR1 coiled-coil domain of Cavin1. We identify specific nanobodies that do not perturb Cavin1 membrane binding and localise to caveolae when expressed in cells. The crystal structure of a nanobody HR1 complex reveals a symmetric 3:3 architecture as validated by mutagenesis. In this structure, the C-terminal half of the HR1 domain is disordered suggesting the nanobody has stabilised an open conformation previously identified as important for membrane interactions. Mutational analysis of a conserved buried hydrogen-bonded His-Thr pair proximal to this region reveals selective regulation of cavin2/cavin3 association. These studies provide new insights into Cavin domains required for assembly of multiprotein caveolar assemblies and describe new nanobody tools for structural and functional studies of caveolae.
Differential effects of statins on the anti-dyskinetic activity of sub-anesthetic ketamine
Authors: Bartlett Mitchell J. , Stopera Carolyn J. , Cowen Stephen L. , Sherman Scott J. , Falk Torsten 
Published: November 2024

AbstractSub-anesthetic ketamine has been demonstrated to reduce abnormal involuntary movements (AIMs) in preclinical models of L-DOPA-induced dyskinesia (LID) and retrospective Parkinson’s disease case reports. In this study, we examined the effects on L-DOPA-induced dyskinesia of two statins alone and in combination with ketamine in unilateral 6-hydroxydopamine-lesioned male rats, the standard preclinical LID model. Sub-anesthetic ketamine attenuated the development of AIMs, while lovastatin only showed anti-dyskinetic activity at the beginning of the priming but did not prevent the development of LID. The polar pravastatin blocked the long-term anti-dyskinetic effects of ketamine, while the non-polar lovastatin did not. This study shows different classes of statins affect LID differentially, points to an important drug interaction and further supports ongoing clinical testing of sub-anesthetic ketamine to treat LID in individuals with Parkinson’s disease.
Genome-wide association study of frost tolerance inVicia fabareveals syntenic loci in cool-season legumes and highlights relevant candidate genes
Authors: Imbert Baptiste , Kreplak Jonathan , Lejeune-Hénaut Isabelle , Magnin-Robert Jean-Bernard , Boutet Gilles , Marget Pascal , Aubert Grégoire , Burstin Judith , Tayeh Nadim 
Published: November 2024

AbstractCool-season grain legumes are mostly grown over spring and summer due to poor frost tolerance. However, fall-sown varieties often provide higher yields, earlier harvests and avoid late-season drought and heat. Understanding the genetic determinism and molecular basis of frost tolerance is therefore crucial for developing high-performing winter varieties. This study aimed to (1) investigate the genetic architecture of frost tolerance inVicia fabaL. using 247 accessions phenotyped under four field environments, and (2) explore the conservation of frost tolerance loci in cool-season legumes using the OrthoLegKB translational research database. A genome-wide association study identified nineteenV. fabagenomic regions with a high density of markers significantly associated with frost tolerance, on all chromosomes. Mapping of frost tolerance QTL fromV. fabaand related species obtained from the literature onto their respective reference genomes and their integration into OrthoLegKB revealed synteny of major QTL acrossV. faba,Pisum sativum, and/orMedicago truncatula, particularly near clusters ofCBF/DREB1genes. Frost tolerance QTL at theP. sativum Lelocus, which controls internode length, were also syntenic with a frost tolerance QTL inV. faba. Synteny between frost tolerance QTL and those controlling phenology and physiology was found at other loci, suggesting pleiotropy. Finally, expression data fromP. sativumandC. arietinumaccessions grown under low temperature were considered as information source to highlight potential candidate genes underlying the conserved QTL. Overall, these results provide a valuable resource for understanding and improving frost tolerance inV. fabaand other cool-season legumes, including orphan crops by knowledge transfer. The use of OrthoLegKB to explore the genetic and molecular determinism of target traits across species is worth generalising.
SNMF: Integrated Learning of Mutational Signatures and Prediction of DNA Repair Deficiencies
Authors: Goossens Sander , Tepeli Yasin I. , Seale Colm , Gonçalves Joana P. 
Published: November 2024

AbstractMotivationMany tumours show deficiencies in DNA damage response (DDR), which influence tumorigenesis and progression, but also expose vulnerabilities with therapeutic potential. Assessing which patients might benefit from DDR-targeting therapy requires knowledge of tumour DDR deficiency status, with mutational signatures reportedly better predictors than loss of function mutations in select genes. However, signatures are identified independently using unsupervised learning, and therefore not optimised to distinguish between different pathway or gene deficiencies.ResultsWe propose SNMF, a supervised non-negative matrix factorisation that jointly optimises the learning of signatures: (1) shared across samples, and (2) predictive of DDR deficiency. We applied SNMF to mutation profiles of human induced pluripotent cell lines carrying gene knockouts linked to three DDR pathways. The SNMF model achieved high accuracy (0.971) and learned more complete signatures of the DDR status of a sample, further discerning distinct mechanisms within a pathway. Cell line SNMF signatures recapitulated tumour-derived COSMIC signatures and predicted DDR pathway deficiency of TCGA tumours with high recall, suggesting that SNMF-like models can leverage libraries of induced DDR deficiencies to decipher intricate DDR signatures underlying patient tumours.Availabilityhttps://github.com/joanagoncalveslab/SNMF.
Pubertal hormones and the early adolescent female brain: a multimodality brain MRI study
Authors: Khetan Muskan , Vijayakumar Nandita , Tian Ye Ella , Herting Megan M. , Connell Michele O’ , Seal Marc , Whittle Sarah 
Published: November 2024

ABSTRACTPuberty is a critical developmental process that is associated with changes in steroid hormone levels, which are believed to influence adolescent behaviour via their effects on the developing brain. So far, there are limited and inconsistent findings regarding the relationship between steroid hormones and brain structure and function in adolescent females, with many existing studies employing small sample sizes. Thus, in this study, we explored the association between oestradiol (E2), testosterone (Tes) and dehydroepiandrosterone (DHEA) and brain structure (gray matter volume, sulcal depth, cortical thickness and white matter microstructure) and function (resting-state connectivity, emotional n-back task-related function) in 3024 adolescent females (age 8.92 - 13.33 years, mean age (SD) = 10.37 (0.94) years) from the Adolescent Brain Cognitive DevelopmentSM(ABCD®) Study. We used elastic-net regression with cross- validation to investigate associations between hormones and brain phenotypes derived from multiple imaging modalities. We found that structural brain features, including cortical thickness, sulcal depth, and white matter microstructure, were among the most important features associated with hormones. E2 was most strongly associated with prefrontal and premotor regions involved in working memory and emotion processing, while Tes and DHEA were most strongly associated with parietal and occipital regions involved in visuospatial functioning. All three hormones were also associated with prefrontal, temporoparietal junction and insula cortices. Thus, using an advanced methodological approach, this study suggests both unique and overlapping neural correlates of pubertal hormones in adolescent females and sheds light on the mechanisms by which puberty influences adolescent development and behaviour.
A 2022 avian H5N1 influenza A virus from clade 2.3.4.4b attaches to and replicates better in human respiratory epithelium than a 2005 H5N1 virus from clade 2.3.2.1
Authors: Bauer Lisa , Leijten Lonneke , Iervolino Matteo , Chopra Varun , van Dijk Laura , Power Mark , Spronken Monique , Rijnink Willemijn , Funk Mathis , de Vries Rory D. , Richard Mathilde , Kuiken Thijs , van Riel Debby 
Published: November 2024

AbstractBackgroundHighly pathogenic avian influenza (HPAI) H5 viruses of the A/Goose/Guangdong/1/1996 (GsGd) lineage pose significant global risks to wildlife, domestic animals, and humans. Recent cross-species transmission events to mammals, including humans, highlight this risk. Critical determinants for cross-species and intra-species transmission include the ability to attach to and replicate in respiratory epithelial cells. Although these factors have been studied for HPAI H5N1 viruses in the past, limited studies are available for currently circulating strains.MethodsWe compared level of adaptation to human respiratory tract of a HPAI H5N1 clade 2.3.4.4b (H5N12022) virus with those of well characterized HPAI H5N1 clade 2.1.3.2 (H5N12005) and seasonal H3N22003viruses by three methods. First, we compared pattern of virus attachment by virus histochemistry. Second, we compared efficiency of infection and replication, as well as innate immune responses in human respiratory epitheliumin vitro. Lastly, we compared polymerase complex activity in a minigenome assay.FindingsThe H5N12022virus attached more abundantly to and replicated more efficiently in cells of the human respiratory tract compared to H5N12005and H3N2 viruses. This increased replication was not associated with an increased polymerase activity of H5N12022virus compared to H3N22003virus. The efficient replication of H5N12022virus infection induced a robust innate immune response almost comparable to H3N22003.InterpretationThe pattern of virus attachment and replication efficiency of a HPAI H5N12022virus resembled that of H3N22003virus more closely than a HPAI H5N12005. This could contribute to an increased risk for both human infection and virus adaptations to humans.FundingThe Netherlands Organization for Health Research and DevelopmentResearch in contextEvidence before this studyHighly pathogenic avian influenza (HPAI) H5 viruses of the A/Goose/Guangdong/1/1996 (GsGd) lineage (clade 2.3.4.4b) have the ability to spread to a wide range of domesticated and wild mammalian species, including humans. Cross species transmission and transmission among humans requires— among other factors—efficient infection of epithelial cells in the respiratory epithelium of the upper respiratory tract.Added value of this studyIn our study we show that a recent clade 2.3.4.4b HPAI H5N1 virus attached to and replicated more efficiently in respiratory epithelium than a clade 2.1.3.2 H5N1 virus that circulated in 2005.Implications of all the available dataThese data suggest that there might be an increased risk of human infections with the currently circulating 2.3.4.4b HPAI H5N1 viruses, which might facilitate opportunities for human adaptation.
Genomic characterization and functional insights of multidrug-resistantKlebsiella pneumoniaestrain BCSIR-JUMIID
Authors: Faruk Mohammad Omar , Sarkar Md. Murshed Hasan , Hossain MD Ismail , Shabuj Abdullah Al-Mamun , Bhim Manotush , Mehzabin Kaniz , Chowdhury Sanjana Fatema , Naser Showti Raheel , Mumtaz Tabassum , Ahmed Md Firoz 
Published: November 2024

AbstractKlebsiella pneumoniaeis a prominent opportunistic pathogen associated with multidrug resistance (MDR) and high morbidity and mortality rates in healthcare settings. The emergence of strains resistant to last-resort antibiotics, such as colistin and carbapenems, poses significant therapeutic challenges. This study presents the complete genome analysis of the MDR strainK. pneumoniaeBCSIR-JUMIID to elucidate its genetic architecture, resistance mechanisms, and virulence factors. The genome ofK. pneumoniaeBCSIR-JUMIID, isolated from a pharmaceutical wastewater in Dhaka, Bangladesh, was sequenced using next-generation sequencing technologies. Bioinformatics tools were employed for genome assembly, annotation, and functional analysis. Phylogenetic relationships were established through whole-genome comparisons. Antibiotic resistance genes, virulence factors, and mobile genetic elements were identified using the Comprehensive Antibiotic Resistance Database (CARD), ResFinder-4.5.0, Virulence Factors Database (VFDB), and various phage identification tools. The genome ofK. pneumoniaeBCSIR-JUMIID consists of 5,769,218 bp with a G+C content of 56.79%, assembled into 343 contigs. A total of 6,062 coding sequences (CDS), including 1,087 hypothetical proteins, 49 tRNA genes, and 4 rRNA genes, were identified. Key loci involved in capsular polysaccharide and O-antigen biosynthesis (KL150, KL107-D1, O3b) were detected. A diverse array of antibiotic resistance genes was uncovered, including those conferring resistance to beta-lactams, quinolones, and colistin. Phage analysis revealed the presence of multiple dsDNA bacteriophages, and CRISPR-Cas systems indicated robust phage defense mechanisms. The genomic analysis ofK. pneumoniaeBCSIR-JUMIID provides a detailed understanding of its resistance and virulence mechanisms, highlighting its potential for horizontal gene transfer and rapid adaptation. These findings underscore the necessity for continued surveillance and novel therapeutic strategies to combat MDRK. pneumoniaeinfections effectively.
The swarming behaviors of Vorticella
Authors: Tabata Tetsuya , Maeyama Yuko 
Published: November 2024

AbstractTwo Vorticella species undergo a synchronous transition from sessile zooids to motile telotrochs, which swarm enveloped in secreted mucus, subsequently forming dense aggregations on substrates and reverting to the zooid form. This cyclical process recurs on a daily basis. Each species exhibits a unique mode of swarming behavior. We hypothesize that these behaviors may serve to facilitate efficient feeding while concurrently acting as a mechanism for predator avoidance.
RewiringEscherichia colito Transform Formate into Methyl Groups
Authors: Mohr Michael K. F. , Satanowski Ari , Lindner Steffen N. , Erb Tobias J. , Andexer Jennifer N. 
Published: November 2024

AbstractBackgroundBiotechnological applications are steadily growing and have become an important tool to reinvent the synthesis of chemicals and pharmaceuticals for lower dependence on fossil resources. In order to sustain this progression, new feedstocks for biotechnological hosts have to be explored. One-carbon (C1-)compounds, including formate, derived from CO2or organic waste are accessible in large quantities with renewable energy, making them promising candidates. Previous studies showed that introduction of the formate assimilation machinery fromMethylorubrum extorquensintoEscherichia coliallows assimilation of formate into the established biotechnological host. Applying this established route for formate assimilation, we here investigated utilisation of formate for the production of value-added building blocks inE. coli using S-adenosylmethionine (SAM)-dependent methyltransferases.ResultsWe first analysed methylation activity inE. coliBL21with a two-vector system to produce three different methyltransferases together with the formate assimilation machinery.Feeding isotopically labelled formate, products with 51 – 81%13C-labelling could be obtained by maintainingin vivomethylation activity. Focussing on improvement ofin vivomethylation, we analysed two furtherE. colistrains with an engineered C1-metabolism and, following condition optimisation, achieved a doubled methylation activity with a share of more than 70% formate-derived methyl groups.ConclusionsThis study demonstrates the efficient transformation of formate into methyl groups inE. coli. Our findings support that feeding formate can improve the availability of usable C1-compounds and, as a result, increasein vivomethylation activity in engineeredE. coli.
Unexplored Yeast diversity in Seed Microbiota
Authors: Marchi Muriel , Bosc-Bierne Anaïs , Lerenard Thomas , Le Corff Josiane , Aligon Sophie , Rolland Aurélia , Simonin Marie , Marais Coralie , Briand Martial , Cordovez Viviane , Gouka Linda , Guillemette Thomas , Simoneau Philippe , Guschinskaya Natalia 
Published: November 2024

AbstractYeasts are known to be fantastic biotechnological resources for medical, food, and industrial applications, but their potential remains untapped in agriculture, especially for plant biostimulation and biocontrol. In particular, yeasts have been reported as part of the core microbiome of seeds using next generation sequencing methods, but their diversity and functional roles remain largely undescribed. This study aimed to fill this knowledge gap by characterizing the diversity of seed-associated yeasts across nine plant species (crops and non-cultivated species) using culturomics, microscopy, and metabarcoding.Our results show that seed-associated yeasts largely belong to Basidiomycota phylum and more particularly to the Tremellomycetes class. This yeast collection covers 15 genera (2 of Ascomycota and 13 of Basidiomycota). Out of the 219 isolates described, the most frequently isolated yeasts wereHoltermaniella, Vishniacozyma, Filobasidium, NaganishiaandSporobolomyces. The yeasts from these dominant genera were isolated from multiple plant species (4 to 8), except forNaganishiawhich only originated fromSolanum lycopersicum L.. These results are also consistent with the fact that these dominant taxa were recently identified as members of the core seed microbiome, indicating their high prevalence and abundance across diverse plant hosts and environments. Compared to previous plant yeast diversity surveys, the members from Ascomycota are less frequent in seeds and only represented here by theAureobasidiumandTaphrinagenera. Altogether, these results suggest that yeasts are generally well-adapted to the aboveground habitats of plants, but seeds represent a specific habitat that diverse Basidiomycota yeasts can colonize.Take away message219 yeasts isolated from seeds and seedlings of diverse plant speciesMost isolates are Basidiomycota yeasts, especially of the Tremellomycetes classAscomycota yeasts are rarely isolated from the seed environmentThe most frequently isolated yeasts belong toHoltermaniella, Vishniacozyma, FilobasidiumandSporobolomycesgeneraThe collection is representative of taxa found in seed microbiota of multiple plant species