bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dependence of aerosol-borne influenza A virus infectivity on relative humidity and aerosol composition
Authors: Motos Ghislain , Schaub Aline , David Shannon C. , Costa Laura , Terrettaz Céline , Kaltsonoudis Christos , Glas Irina , Klein Liviana K. , Bluvshtein Nir , Luo Beiping , Violaki Kalliopi , Pohl Marie O. , Hugentobler Walter , Krieger Ulrich K. , Pandis Spyros N. , Stertz Silke , Peter Thomas , Kohn Tamar , Nenes Athanasios 
Published: May 2024

AbstractWe describe a novel biosafety aerosol chamber equipped with state-of-the-art instrumentation for bubble-bursting aerosol generation, size distribution measurement, and condensation-growth collection to minimize sampling artifacts when measuring virus infectivity in aerosol particles. Using this facility, we investigated the effect of relative humidity (RH) in very clean air without trace gases (except ∼400 ppm CO2) on the preservation of influenza A virus (IAV) infectivity in saline aerosol particles. We characterized infectivity in terms of 99%-inactivation time,t99, a metric we consider most relevant to airborne virus transmission. The viruses remained infectious for a long time, namelyt99> 5 h, if RH < 30% and the particles effloresced. Under intermediate conditions of humidity (40% < RH < 70%), the loss of infectivity was the most rapid (t99≈ 15-20 min, and up tot99≈ 35 min at 95% RH). This is more than an order of magnitude faster than suggested by many previous studies of aerosol-borne IAV, possibly due to the use of matrices containing organic molecules, such as proteins, with protective effects for the virus. We tested this hypothesis by adding sucrose to our aerosolization medium and, indeed, observed protection of IAV at intermediate RH (55 %). Interestingly, thet99of our measurements are also systematically lower than those in 1-μL droplet measurements of organic-free saline solutions, which cannot be explained by particle size effects alone.
Activity-Based Protein Profiling IdentifiesKlebsiella pneumoniaeSerine Hydrolases with Potential Roles in Host-Pathogen Interactions
Authors: Uddin Md Jalal , Randall George , Zhu Jiyun , Upadhyay Tulsi , van Eijk Laura , Stege Paul B. , Masson Frerich M. , Viveen Marco C. , Bogyo Matthew , Fellner Matthias , de Zoete Marcel R. , Johannessen Mona , Lentz Christian S. 
Published: May 2024

AbstractKlebsiella pneumoniaeis a normal resident of the human gastro-intestinal tract and an opportunistic, critical priority pathogen that can cause a variety of severe systemic infections. Due to emerging multi-drug resistance of this pathogen, the discovery and validation of novel targets for the development of new treatment options is an urgent priority. Here, we explored the family of serine hydrolases, a highly druggable and functionally diverse enzyme family which is uncharacterized inK. pneumoniae. Using functionalized covalent fluorophosphonate inhibitors as activity-based probes we identified 10 serine hydrolases by mass spectrometry-based activity-based protein profiling, 7 of which were previously uncharacterized. Functional validation using transposon mutants deficient in either of the putative lysophospholipase PldB, esterase YjfP and patatin-like phospholipase YchK revealed severe growth defects in human colonic organoid co-culture models and reduced virulence duringGalleria mellonellainfection. Mutants deficient in the PldB and YjfP, but not YchK show increased susceptibility to killing by complement and the antimicrobial peptide antibiotic polymyxin B, suggesting a role in maintaining cell envelope integrity. Biochemical characterization and structural analysis of recombinant YjfP suggest this protein is a deacetylase. This study gives important insights into the molecular mechanisms underlying virulence and cell physiology ofK. pneumoniaeat the host-pathogen interface and it positions PldB, YjfP and YchK as potential antimicrobial or anti-virulence target candidates, inhibition of which might synergize with existing antibiotics and human immune defenses.
Deficiency of the histone lysine demethylase KDM5B causes autism-like phenotypes via increased NMDAR signalling
Authors: Pérez-Sisqués Leticia , Bhatt Shail U. , Caruso Angela , Ahmed Mohi U. , Gileadi Talia E. , Spring Shoshana , Hendy Eleanor , Taylor-Papadimitriou Joyce , Cash Diana , Clifton Nicholas , Ellegood Jacob , Andreae Laura C. , Lerch Jason P. , Scattoni Maria Luisa , Giese K. Peter , Fernandes Cathy , Basson M. Albert 
Published: May 2024

AbstractLoss-of-function mutations in genes encoding lysine methyltransferases (KMTs) and demethylases (KDMs) responsible for regulating the trimethylation of histone 3 on lysine 4 (H3K4me3) are associated with neurodevelopmental conditions, including autism spectrum disorder and intellectual disability. To study the specific role of H3K4me3 demethylation, we investigated neurodevelopmental phenotypes in mice without KDM5B demethylase activity. These mice exhibited autism-like behaviours and increased brain size. H3K4me3 levels and the expression of neurodevelopmental genes were increased in the developingKdm5bmutant neocortex. These included elevated expression ofGrin2d. TheGrin2dgene product NMDAR2D was increased in synaptosomes isolated from theKdm5b-deficient neocortex and treating mice with the NMDAR antagonist memantine rescued deficits in ultrasonic vocalisations and reduced repetitive digging behaviours. These findings suggest that increased H3K4me3 levels and associatedGrin2dgene upregulation disrupt brain development and function, leading to socio-communication deficits and repetitive behaviours, and identify a potential therapeutic target for neurodevelopmental disorders associated with KDM5B deficiency.
ActiveE. coliheteromeric acetyl-CoA carboxylase forms polymorphic helical tubular filaments
Authors: Xu Xueyong , Silva de Sousa Amanda , Boram Trevor J. , Jiang Wen , Lohman Jeremy R. 
Published: May 2024

AbstractTheEscherichia coliheteromeric acetyl-CoA carboxylase (ACC) has four subunits assumed to form an elusive catalytic complex and are involved in allosteric and transcriptional regulation. TheE. coliACC represents almost all ACCs from pathogenic bacteria making it a key antibiotic development target to fight growing antibiotic resistance. Furthermore, it is a model for cyanobacterial and plant plastid ACCs as biofuel engineering targets. Here we report the catalyticE. coliACC complex surprisingly forms tubes rather than dispersed particles. The cryo-EM structure reveals key protein-protein interactions underpinning efficient catalysis and how transcriptional regulatory roles are masked during catalysis. Discovering the protein-protein interaction interfaces that facilitate catalysis, allosteric and transcriptional regulation provides new routes to engineering catalytic activity and new targets for drug discovery.One-Sentence SummaryBacterial heteromeric acetyl-CoA carboxylase forms tubes to promote efficient catalysis and mask transcriptional regulation.
High-resolution 2D Solid-State NMR provides insights into Nontuberculous Mycobacteria
Authors: Byeon Chang-Hyeock , Hansen Kasper Holst , DePas William , Akbey Ümit 
Published: May 2024

AbstractWe present a high-resolution magic-angle spinning (MAS) solid-state NMR (ssNMR) study to characterize native nontuberculous mycobacteria (NTM). We studied two different NTM strains,Mycobacterium smegmatis, a model, non-pathogenic strain, andMycobacterium abscessus, an emerging and important human pathogen. Native hydrated NTM samples were studied at natural abundance without isotope-labelling and any chemical or physical modification. We utilized 1D13C and 2D1H-13C ssNMR spectra and peak deconvolution to identify NTM cell-wall chemical sites. More than ∼100 distinct13C signals were identified in the ssNMR spectra. The signals originating from both the flexible and rigid fractions of the native bacteria samples were selectively analyzed by utilizing either CP or INEPT based13C ssNMR spectra. CP buildup curves provide insights into the dynamical similarity of the cell-wall components for NTM strains. Signals from peptidoglycan, arabinogalactan and mycolic acid were identified. We also provide tentative assignments for ∼30 polysaccharides by using well resolved1H/13C chemical shifts from the 2D INEPT-based1H-13C ssNMR spectrum. As an orthogonal way of characterizing the bacteria, electron microscopy (EM) was used to provide spatial characterization. ssNMR and EM data suggest thatM. abscessuscell-wall is composed of a smaller peptidoglycan layer which is more flexible compared toM. smegmatis, which may be related to its higher pathogenicity. Here in this work, we used high-resolution 2D ssNMR first time to characterize native NTM strains and identified chemical sites. These results will aid the development of structure-based approaches to combat NTM infections.
Piezo1 ion channels are capable of conformational signaling
Authors: Lewis Amanda H. , Cronin Marie E. , Grandl Jörg 
Published: May 2024

SummaryPiezo1 is a mechanically activated ion channel that senses forces with short latency and high sensitivity. Piezos undergo large conformational changes, induce far-reaching deformation onto the membrane, and modulate the function of two-pore potassium (K2P) channels. Taken together, this led us to hypothesize that Piezos may be able to signal their conformational state to other nearby proteins. Here, we use chemical control to acutely restrict Piezo1 conformational flexibility and show that Piezo1 conformational changes, but not ion permeation through it, are required for modulating the K2P channel TREK1. Super-resolution imaging and stochastic simulations further reveal that both channels do not co-localize, which implies that modulation is not mediated through direct binding interactions; however, at high Piezo1 densities, most TREK1 channels are within the predicted Piezo1 membrane footprint, suggesting the footprint may underlie conformational signaling. We speculate that physiological roles originally attributed to Piezo1 ionotropic function could, alternatively, involve conformational signaling.
Detection of neutralizing antibodies against arboviruses from liver homogenates
Authors: Costa Thais Alkifeles , Arruda Matheus Soares , Oliveira Gabriela Fernanda Garcia , de Sousa Reis Erik Vinicius , Guimarães Anna Catarina Dias Soares , Moreira Gabriel Dias , Arias Nidia Esther Colquehuanca , do Vale Beirão Marina , Vasilakis Nikos , Hanley Kathryn A. , Drumond Betânia Paiva 
Published: May 2024

ABSTRACTYellow fever virus (YFV) circulates in a sylvatic cycle between non-human primates (NHPs) and arboreal mosquitoes in Brazil. Passive monitoring of ill or deceased NHPs is a key component of the Brazilian yellow fever (YF) surveillance program. Samples from NHPs carcasses are usually suitable for molecular tests but not for serological assays. As an alternative to the conventional plaque reduction neutralization test (PRNT) based on sera, we tested the utility of liver homogenates from experimentally infected (YFV, Mayaro virus [MAYV], chikungunya virus [CHIKV], or mock) mice to quantify PRNTs. Although homogenates from mock-infected mice showed a low level of nonspecific virus neutralization against YFV, MAYV or CHIKV, homogenates from YFV-, MAYV- and CHIKV-infected mice demonstrated significantly higher levels of virus neutralization compared to controls. Receiver operating characteristic (ROC) curves analyses were performed using the median neutralization values of three technical replicates for each infected group separately or collectively. Results showed scores ≥0.97 (95% CI ≥ 0.89-1.0) for the area under the curve at dilutions 1:20 to 1:80, suggesting that median virus neutralization values effectively differentiated YFV-, MAYV-, or CHIKV-infected groups from controls. Liver homogenates obtained from 25 NHPs carcasses (collected during the 2017 YF outbreak in Brazil) were also tested using the adapted PRNT as well as rapid anti-YFV IgM immunochromatographic tests. Neutralization activity was detected in six NHPs samples that were also positive by PCR and anti-YFV IgM tests and one sample that tested negative by PCR and IgM test. Our results demonstrate the feasibility of using liver homogenates as an alternative approach for serological investigation in viral epidemiologic surveillance.
Quantifying acyl-chain diversity in isobaric compound lipids containing monomethyl branched-chain fatty acids
Authors: Green CR , Kolar MJ , McGregor GH , Nelson AT , Wallace M , Metallo CM 
Published: May 2024

AbstractCompound lipids comprise a diverse group of metabolites present in living systems, and metabolic- and environmentally-driven structural distinctions across this family is increasingly linked to biological function. However, methods for deconvoluting these often isobaric lipid species are lacking or require specialized instrumentation. Notably, acyl-chain diversity within cells may be influenced by nutritional states, metabolic dysregulation, or genetic alterations. Therefore, a reliable, validated method of quantifying structurally similar even-, odd-, and branched-chain acyl groups within intact compound lipids will be invaluable for gaining molecular insights into their biological functions. Here we demonstrate the chromatographic resolution of isobaric lipids containing distinct combinations of straight-chain and branched-chain acyl groups via ultra-high-pressure liquid chromatography (UHPLC)-mass spectrometry (MS) using a C30 liquid chromatography column. Using metabolically-engineered adipocytes lacking branched-keto acid dehydrogenase A (Bckdha), we validate this approach through a combination of fatty acid supplementation and metabolic tracing using monomethyl branched-chain fatty acids and valine. We observe resolution of numerous isobaric triacylglycerols and other compound lipids, demonstrating the resolving utility of this method. This approach strengthens our ability to quantify and characterize the inherent diversity of acyl chains across the lipidome.
Predicted mechanistic impacts of human protein missense variants
Authors: Jänes Jürgen , Müller Marc , Selvaraj Senthil , Manoel Diogo , Stephenson James , Gonçalves Catarina , Lafita Aleix , Polacco Benjamin , Obernier Kirsten , Alasoo Kaur , Lemos Manuel C. , Krogan Nevan , Martin Maria , Saraiva Luis R. , Burke David , Beltrao Pedro 
Published: May 2024

AbstractGenome sequencing efforts have led to the discovery of tens of millions of protein missense variants found in the human population with the majority of these having no annotated role and some likely contributing to trait variation and disease. Sequence-based artificial intelligence approaches have become highly accurate at predicting variants that are detrimental to the function of proteins but they do not inform on mechanisms of disruption. Here we combined sequence and structure-based methods to perform proteome-wide prediction of deleterious variants with information on their impact on protein stability, protein-protein interactions and small-molecule binding pockets. AlphaFold2 structures were used to predict approximately 100,000 small-molecule binding pockets and stability changes for over 200 million variants. To inform on protein-protein interfaces we used AlphaFold2 to predict structures for nearly 500,000 protein complexes. We illustrate the value of mechanism-aware variant effect predictions to study the relation between protein stability and abundance and the structural properties of interfaces underlyingtransprotein quantitative trait loci (pQTLs). We characterised the distribution of mechanistic impacts of protein variants found in patients and experimentally studied example disease linked variants in FGFR1.
The genusCortinariusshould not (yet) be split
Authors: Gallone Brigida , Kuyper Thomas W. , Nuytinck Jorinde 
Published: May 2024

AbstractThe genusCortinarius(Pers.) Gray (Agaricales, Basidiomycota) is one of the most species-rich fungal genera with thousands of species reported.Cortinariusspecies are important ectomycorrhizal fungi and form associations with many vascular plants globally. Until recentlyCortinariuswas the single genus of theCortinariaceaefamily, despite several attempts to provide a workable, lower-rank hierarchical structure based on subgenera and sections. The first phylogenomic study for this group elevated the old genusCortinariusto family level and the family was split into ten genera, of which seven were described as new. Here, by careful re-examination of the recently published phylogenomic dataset, we detected extensive gene-tree/species-tree conflicts using both concatenation and multispecies coalescent (MSC) approaches. Our analyses demonstrate that theCortinariusphylogeny remains unresolved and the resulting phylogenomic hypotheses suffer from very short and unsupported branches in the backbone. We can confirm monophyly of only four out of ten suggested new genera, leaving uncertain the relationships between each other and the general branching order. Thorough exploration of the tree space demonstrated that the topology on whichCortinariusrevised classification relies on does not represent the best phylogenetic hypothesis and should not be used as constrained topology to include additional species.For this reason, we argue that based on available evidence the genusCortinariusshould not (yet) be split.Moreover, considering that phylogenetic uncertainty translates to taxonomic uncertainty, we advise for careful evaluation of phylogenomic datasets before proposing radical taxonomic and nomenclatural changes.
The dual actions of the host miRNA-16a in restricting Bovine coronavirus (BCoV) replication through targeting host cell Furin and in enhancing the host immune response
Authors: Shah Abid Ullah , Hemida Maged Gomaa 
Published: May 2024

1.AbstractThe roles of host cell miRNAs have not been studied well in the context of BCoV replication and immune regulation. The main aim of this study was to identify some miRNA candidates that regulate essential host genes involved in BCoV replication, tissue tropism, and immune regulation. To achieve these goals, we used two isolates of BCoV (enteric and respiratory) to infect the bovine endothelial cells (BEC) and Madine Darby Bovine Kidney (MDBK) cells. This is in addition to the ex vivo model using the peripheral bovine blood mononuclear cells (PBMC). We determined the miRNA expression profiles in these cells after BCoV infection. miRA-16a is one of the differentially altered during BCoV infection. Our data shows that miRNA-16a is a significantly downregulated miRNA in both in vitro andex vivomodels. We confirmed the miRNA-16a expression profile by the qRT-PCR. Overexpression of the pre-miRNA-16a in BEC and MDBK cell lines resulted in marked inhibition of BCoV infection based on the viral genome copy numbers measured by qRT-PCR, the viral protein expression (S and N) measured by Western blot, and the virus infectivity using plaque assay. Our bioinformatic prediction showed that Furin is a potential target for the miRNA-16a. We checked the Furin protein expression level in the pre-miRNA-16a transfected/BCoV infected cells compared to the pre-miRNA scrambled to validate that. Our data shows marked inhibition of the Furin expression levels on the mRNA levels by qRT-PCR and the protein level by Western blot. The BCoV-S protein expression was markedly inhibited on both the mRNA and protein levels. To further confirm the impacts of the downregulation of the Furin enzyme on the replication of BCoV, we used transfected cells with specific Furin-siRNA parallel to the scrambled siRNA. A marked inhibition of BCoV replication was observed in the Furin-siRNA-treated group. To further validate Furin as a novel target for miRNA-16a, we cloned the 3’UTR of the bovine Furin carrying the seed region of the miRNA-16a in the dual luciferase vector. Our data shows luciferase activity in the pre-miRNA-16a transfected cells decreased by more than 50% compared to the cells transfected with the construct carrying the mutated Furin seed region. Our data confirms miRNA-16a inhibits BCoV replication by targeting the host cell Furin and the BCoV-S glycoprotein. It will also enhance the host immune response, which contributes to the inhibition of viral replication. To our knowledge, this is the first study to confirm that Furin is a valid target for the miRNA-16a. Our findings highlight the clinical applications of the host miRNA-16a as a potential miRNA-based vaccine/antiviral therapy.
Real-time correlators in
3+1D
thermal lattice gauge theory
Authors: Boguslavski Kirill , Hotzy Paul , Müller David I. 
Published: May 2024

We present the first direct computation of unequal-time correlation functions in non-Abelian lattice gauge theory. We demonstrate nontrivial consistency relations among correlators, time-translation invariance, and agreement with Monte Carlo results for thermal equilibrium in 3+1 dimensions by employing our stabilized complex Langevin method. Our work sets the stage to extract real-time observables, relevant to quark-gluon plasma physics within a first-principles real-time framework.

Published by the American Physical Society
2024
FinTech and financial development: the role of traditional financial institutions
Authors: Emuron Abraham , van der Nest D.P. , Coffie Cephas Paa Kwasi 
Published: May 2024

PurposeThis paper employs data from the World Bank to examine the effect of traditional banks on FinTech and financial development in the Southern African Development Community (SADC) region.Design/methodology/approachThe study employs the Generalized Method of Moments (GMM) as the primary data analysis method.FindingsThe findings of the study demonstrate a bi-directional relationship between traditional financial institutions and FinTech. Traditional financial institutions are observed to facilitate the adoption of FinTech solutions, whilst the disruptive effects of FinTech incentivize traditional banks to adapt to the changing financial landscape and tailor their service and product offerings to reflect recent technological advancements. Consequently, there exists a positive relationship between traditional financial institutions and financial development in the SADC region.Practical implicationsOur findings suggest the need for market liberalization and enhanced institutional quality controls for policymakers. Traditional banks must adapt their business models and incorporate FinTech solutions to remain competitive and relevant. Collaborative partnerships between traditional banks and FinTech firms have emerged as a practical approach to leverage the strengths of both sectors.Originality/valueThis is one of the first studies to examine the role of traditional financial institutions in FinTech and financial development using GMM in the SADC region.