bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting fungal membrane homeostasis with imidazopyrazoindoles impairs azole resistance and biofilm formation
Authors: Revie Nicole M. , Iyer Kali R. , Maxson Michelle E. , Zhang Jiabao , Yan Su , Fernandes Caroline M. , Meyer Kirsten J. , Chen Xuefei , Skulska Iwona , Fogal Meea , Sanchez Hiram , Hossain Saif , Li Sheena , Yashiroda Yoko , Hirano Hiroyuki , Yoshida Minoru , Osada Hiroyuki , Boone Charles , Shapiro Rebecca S. , Andes David R. , Wright Gerard D. , Nodwell Justin R. , Del Poeta Maurizio , Burke Martin D. , Whitesell Luke , Robbins Nicole , Cowen Leah E. 
Published: June 2022

AbstractFungal infections cause more than 1.5 million deaths annually. With an increase in immune-deficient susceptible populations and the emergence of antifungal drug resistance, there is an urgent need for novel strategies to combat these life-threatening infections. Here, we use a combinatorial screening approach to identify an imidazopyrazoindole, NPD827, that synergizes with fluconazole against azole-sensitive and -resistant isolates of Candida albicans. NPD827 interacts with sterols, resulting in profound effects on fungal membrane homeostasis and induction of membrane-associated stress responses. The compound impairs virulence in a Caenorhabditis elegans model of candidiasis, blocks C. albicans filamentation in vitro, and prevents biofilm formation in a rat model of catheter infection by C. albicans. Collectively, this work identifies an imidazopyrazoindole scaffold with a non-protein-targeted mode of action that re-sensitizes the leading human fungal pathogen, C. albicans, to azole antifungals.
Defect-induced monopole injection and manipulation in artificial spin ice
Authors: Puttock Robert , Andersen Ingrid M. , Gatel Christophe , Park Bumsu , Rosamond Mark C. , Snoeck Etienne , Kazakova Olga 
Published: June 2022

AbstractLithographically defined arrays of nanomagnets are well placed for application in areas such as probabilistic computing or reconfigurable magnonics due to their emergent collective dynamics and writable magnetic order. Among them are artificial spin ice (ASI), which are arrays of binary in-plane macrospins exhibiting geometric frustration at the vertex interfaces. Macrospin flips in the arrays create topologically protected magnetic charges, or emergent monopoles, which are bound to an antimonopole to conserve charge. In the absence of controllable pinning, it is difficult to manipulate individual monopoles in the array without also influencing other monopole excitations or the counter-monopole charge. Here, we tailor the local magnetic order of a classic ASI lattice by introducing a ferromagnetic defect with shape anisotropy into the array. This creates monopole injection sites at nucleation fields below the critical lattice switching field. Once formed, the high energy monopoles are fixed to the defect site and may controllably propagate through the lattice under stimulation. Defect programing of bound monopoles within the array allows fine control of the pathways of inverted macrospins. Such control is a necessary prerequisite for the realization of functional devices, e. g. reconfigurable waveguide in nanomagnonic applications.
Mucin induces CRISPR-Cas defense in an opportunistic pathogen
Authors: de Freitas Almeida Gabriel Magno , Hoikkala Ville , Ravantti Janne , Rantanen Noora , Sundberg Lotta-Riina 
Published: June 2022

AbstractParasitism by bacteriophages has led to the evolution of a variety of defense mechanisms in their host bacteria. However, it is unclear what factors lead to specific defenses being deployed upon phage infection. To explore this question, we co-evolved the bacterial fish pathogen Flavobacterium columnare and its virulent phage V156 in presence and absence of a eukaryotic host signal (mucin) for sixteen weeks. The presence of mucin leads to a dramatic increase in CRISPR spacer acquisition, especially in low nutrient conditions where over 60% of colonies obtain at least one new spacer. Additionally, we show that the presence of a competitor bacterium further increases CRISPR spacer acquisition in F. columnare. These results suggest that ecological factors are important in determining defense strategies against phages, and that the phage-bacterium interactions on mucosal surfaces may select for the diversification of bacterial immune systems.
Identification and characterization of a new ensemble of cometary organic molecules
Authors: Hänni N. , Altwegg K. , Combi M. , Fuselier S. A. , De Keyser J. , Rubin M. , Wampfler S. F. 
Published: June 2022

AbstractIn-situ study of comet 1P/Halley during its 1986 apparition revealed a surprising abundance of organic coma species. It remained unclear, whether or not these species originated from polymeric matter. Now, high-resolution mass-spectrometric data collected at comet 67P/Churyumov-Gerasimenko by ESA’s Rosetta mission unveil the chemical structure of complex cometary organics. Here, we identify an ensemble of individual molecules with masses up to 140 Da while demonstrating inconsistency of the data with relevant amounts of polymeric matter. The ensemble has an average composition of C1H1.56O0.134N0.046S0.017, identical to meteoritic soluble organic matter, and includes a plethora of chain-based, cyclic, and aromatic hydrocarbons at an approximate ratio of 6:3:1. Its compositional and structural properties, except for the H/C ratio, resemble those of other Solar System reservoirs of organics—from organic material in the Saturnian ring rain to meteoritic soluble and insoluble organic matter –, which is compatible with a shared prestellar history.
Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution
Authors: Monberg Maria E. , Geiger Heather , Lee Jaewon J. , Sharma Roshan , Semaan Alexander , Bernard Vincent , Wong Justin , Wang Fang , Liang Shaoheng , Swartzlander Daniel B. , Stephens Bret M. , Katz Matthew H. G. , Chen Ken , Robine Nicolas , Guerrero Paola A. , Maitra Anirban 
Published: June 2022

AbstractHeterogeneity is a hallmark of cancer. The advent of single-cell technologies has helped uncover heterogeneity in a high-throughput manner in different cancers across varied contexts. Here we apply single-cell sequencing technologies to reveal inherent heterogeneity in assumptively monoclonal pancreatic cancer (PDAC) cell lines and patient-derived organoids (PDOs). Our findings reveal a high degree of both genomic and transcriptomic polyclonality in monolayer PDAC cell lines, custodial variation induced by growing apparently identical cell lines in different laboratories, and transcriptomic shifts in transitioning from 2D to 3D spheroid growth models. Our findings also call into question the validity of widely available immortalized, non-transformed pancreatic lines as contemporaneous “control” lines in experiments. We confirm these findings using a variety of independent assays, including but not limited to whole exome sequencing, single-cell copy number variation sequencing (scCNVseq), single-nuclei assay for transposase-accessible chromatin with sequencing, fluorescence in-situ hybridization, and single-cell RNA sequencing (scRNAseq). We map scRNA expression data to unique genomic clones identified by orthogonally-gathered scCNVseq data of these same PDAC cell lines. Further, while PDOs are known to reflect the cognate in vivo biology of the parental tumor, we identify transcriptomic shifts during ex vivo passage that might hamper their predictive abilities over time. The impact of these findings on rigor and reproducibility of experimental data generated using established preclinical PDAC models between and across laboratories is uncertain, but a matter of concern.
Assembly dynamics of FtsZ and DamX during infection-related filamentation and division in uropathogenic E. coli
Authors: Söderström Bill , Pittorino Matthew J. , Daley Daniel O. , Duggin Iain G. 
Published: June 2022

AbstractDuring infection of bladder epithelial cells, uropathogenic Escherichia coli (UPEC) can stop dividing and grow into highly filamentous forms. Here, we find that some filaments of E. coli UTI89 released from infected cells grow very rapidly and by more than 100 μm before initiating division, whereas others do not survive, suggesting that infection-related filamentation (IRF) is a stress response that promotes bacterial dispersal. IRF is accompanied by unstable, dynamic repositioning of FtsZ division rings. In contrast, DamX, which is associated with normal cell division and is also essential for IRF, is distributed uniformly around the cell envelope during filamentation. When filaments initiate division to regenerate rod cells, DamX condenses into stable rings prior to division. The DamX rings maintain consistent thickness during constriction and remain at the septum until after membrane fusion. Deletion of damX affects vegetative cell division in UTI89 (but not in the model E. coli K-12), and, during infection, blocks filamentation and reduces bacterial cell integrity. IRF therefore involves DamX distribution throughout the membrane and prevention of FtsZ ring stabilization, leading to cell division arrest. DamX then reassembles into stable division rings for filament division, promoting dispersal and survival during infection.
Emergent properties as by-products of prebiotic evolution of aminoacylation ribozymes
Authors: Janzen Evan , Shen Yuning , Vázquez-Salazar Alberto , Liu Ziwei , Blanco Celia , Kenchel Josh , Chen Irene A. 
Published: June 2022

AbstractSystems of catalytic RNAs presumably gave rise to important evolutionary innovations, such as the genetic code. Such systems may exhibit particular tolerance to errors (error minimization) as well as coding specificity. While often assumed to result from natural selection, error minimization may instead be an emergent by-product. In an RNA world, a system of self-aminoacylating ribozymes could enforce the mapping of amino acids to anticodons. We measured the activity of thousands of ribozyme mutants on alternative substrates (activated analogs for tryptophan, phenylalanine, leucine, isoleucine, valine, and methionine). Related ribozymes exhibited shared preferences for substrates, indicating that adoption of additional amino acids by existing ribozymes would itself lead to error minimization. Furthermore, ribozyme activity was positively correlated with specificity, indicating that selection for increased activity would also lead to increased specificity. These results demonstrate that by-products of ribozyme evolution could lead to adaptive value in specificity and error tolerance.
Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines
Authors: Le Vu Stéphane , Bertrand Marion , Jabagi Marie-Joelle , Botton Jérémie , Drouin Jérôme , Baricault Bérangère , Weill Alain , Dray-Spira Rosemary , Zureik Mahmoud 
Published: June 2022

AbstractCases of myocarditis and pericarditis have been reported following the receipt of Covid-19 mRNA vaccines. As vaccination campaigns are still to be extended, we aimed to provide a comprehensive assessment of the association, by vaccine and across sex and age groups. Using nationwide hospital discharge and vaccine data, we analysed all 1612 cases of myocarditis and 1613 cases of pericarditis that occurred in France in the period from May 12, 2021 to October 31, 2021. We perform matched case-control studies and find increased risks of myocarditis and pericarditis during the first week following vaccination, and particularly after the second dose, with adjusted odds ratios of myocarditis of 8.1 (95% confidence interval [CI], 6.7 to 9.9) for the BNT162b2 and 30 (95% CI, 21 to 43) for the mRNA-1273 vaccine. The largest associations are observed for myocarditis following mRNA-1273 vaccination in persons aged 18 to 24 years. Estimates of excess cases attributable to vaccination also reveal a substantial burden of both myocarditis and pericarditis across other age groups and in both males and females.
COVID-19 disease severity in US Veterans infected during Omicron and Delta variant predominant periods
Authors: Mayr Florian B. , Talisa Victor B. , Castro Alexander D. , Shaikh Obaid S. , Omer Saad B. , Butt Adeel A. 
Published: June 2022

AbstractThe SARS-CoV-2 Omicron variant is thought to cause less severe disease among the general population, but disease severity among at-risk populations is unknown. We performed a retrospective analysis using a matched cohort of United States veterans to compare the disease severity of subjects infected during Omicron and Delta predominant periods within 14 days of initial diagnosis. We identified 22,841 matched pairs for both periods. During the Omicron period, 20,681 (90.5%) veterans had mild, 1308 (5.7%) moderate, and 852 (3.7%) severe disease. During the Delta predominant period, 19,356 (84.7%) had mild, 1467 (6.4%) moderate, and 2018 (8.8%) severe disease. Moderate or severe disease was less likely during the Omicron period and more common among older subjects and those with more comorbidities. Here we show that infection with the Omicron variant is associated with less severe disease than the Delta variant in a high-risk older veteran population, and vaccinations provide protection against severe or critical disease.
FANCM promotes class I interfering crossovers and suppresses class II non-interfering crossovers in wheat meiosis
Authors: Desjardins Stuart D. , Simmonds James , Guterman Inna , Kanyuka Kostya , Burridge Amanda J. , Tock Andrew J. , Sanchez-Moran Eugenio , Franklin F. Chris H. , Henderson Ian R. , Edwards Keith J. , Uauy Cristobal , Higgins James D. 
Published: June 2022

AbstractFANCM suppresses crossovers in plants by unwinding recombination intermediates. In wheat, crossovers are skewed toward the chromosome ends, thus limiting generation of novel allelic combinations. Here, we observe that FANCM maintains the obligate crossover in tetraploid and hexaploid wheat, thus ensuring that every chromosome pair exhibits at least one crossover, by localizing class I crossover protein HEI10 at pachytene. FANCM also suppresses class II crossovers that increased 2.6-fold in fancm msh5 quadruple mutants. These data are consistent with a role for FANCM in second-end capture of class I designated crossover sites, whilst FANCM is also required to promote formation of non-crossovers. In hexaploid wheat, genetic mapping reveals that crossovers increase by 31% in fancm compared to wild type, indicating that fancm could be an effective tool to accelerate breeding. Crossover rate differences in fancm correlate with wild type crossover distributions, suggesting that chromatin may influence the recombination landscape in similar ways in both wild type and fancm.
Existing function in primary visual cortex is not perturbed by new skill acquisition of a non-matched sensory task
Authors: Jeon Brian B. , Fuchs Thomas , Chase Steven M. , Kuhlman Sandra J. 
Published: June 2022

AbstractAcquisition of new skills has the potential to disturb existing network function. To directly assess whether previously acquired cortical function is altered during learning, mice were trained in an abstract task in which selected activity patterns were rewarded using an optical brain-computer interface device coupled to primary visual cortex (V1) neurons. Excitatory neurons were longitudinally recorded using 2-photon calcium imaging. Despite significant changes in local neural activity during task performance, tuning properties and stimulus encoding assessed outside of the trained context were not perturbed. Similarly, stimulus tuning was stable in neurons that remained responsive following a different, visual discrimination training task. However, visual discrimination training increased the rate of representational drift. Our results indicate that while some forms of perceptual learning may modify the contribution of individual neurons to stimulus encoding, new skill learning is not inherently disruptive to the quality of stimulus representation in adult V1.
Large Scale Genome-Centric Metagenomic Data from the Gut Microbiome of Food-Producing Animals and Humans
Authors: Lemos Leandro Nascimento , de Carvalho Fabíola Marques , Santos Fernanda Fernandes , Valiatti Tiago Barcelos , Corsi Dandara Cassu , de Oliveira Silveira Alessandro Conrado , Gerber Alexandra , Guimarães Ana Paula C. , de Oliveira Souza Cintya , Brasiliense Danielle Murici , Maia Castelo-Branco Débora de Souza Collares , Anzai Eleine Kuroki , Bessa-Neto Francisco Ozório , de Melo Gláucia Morgana , de Souza Gleyce Hellen , Ferraz Lúcio Fábio Caldas , de Nazaré Miranda Bahia Márcia , Mattos Márcia Soares , da Silva Ramon Giovani Brandão , Veiga Ruanita , Simionatto Simone , Monteiro Walter Aparecido Pimentel , de Oliveira Lima William Alencar , Kiffer Carlos Roberto Veiga , Cayô Rodrigo , Gales Ana Cristina , de Vasconcelos Ana Tereza Ribeiro 
Published: June 2022

AbstractThe One Health concept is a global strategy to study the relationship between human and animal health and the transfer of pathogenic and non-pathogenic species between these systems. However, to the best of our knowledge, no data based on One Health genome-centric metagenomics are available in public repositories. Here, we present a dataset based on a pilot-study of 2,915 metagenome-assembled genomes (MAGs) of 107 samples from the human (N = 34), cattle (N = 28), swine (N = 15) and poultry (N = 30) gut microbiomes. Samples were collected from the five Brazilian geographical regions. Of the draft genomes, 1,273 were high-quality drafts (≥90% of completeness and ≤5% of contamination), and 1,642 were medium-quality drafts (≥50% of completeness and ≤10% of contamination). Taxonomic predictions were based on the alignment and concatenation of single-marker genes, and the most representative phyla were Bacteroidota, Firmicutes, and Proteobacteria. Many of these species represent potential pathogens that have already been described or potential new families, genera, and species with potential biotechnological applications. Analyses of this dataset will highlight discoveries about the ecology and functional role of pathogens and uncultivated Archaea and Bacteria from food-producing animals and humans. Furthermore, it also represents an opportunity to describe new species from underrepresented taxonomic groups.
Optimizing process-based models to predict current and future soil organic carbon stocks at high-resolution
Authors: Pierson Derek , Lohse Kathleen A. , Wieder William R. , Patton Nicholas R. , Facer Jeremy , de Graaff Marie-Anne , Georgiou Katerina , Seyfried Mark S. , Flerchinger Gerald , Will Ryan 
Published: June 2022

AbstractFrom hillslope to small catchment scales (< 50 km2), soil carbon management and mitigation policies rely on estimates and projections of soil organic carbon (SOC) stocks. Here we apply a process-based modeling approach that parameterizes the MIcrobial-MIneral Carbon Stabilization (MIMICS) model with SOC measurements and remotely sensed environmental data from the Reynolds Creek Experimental Watershed in SW Idaho, USA. Calibrating model parameters reduced error between simulated and observed SOC stocks by 25%, relative to the initial parameter estimates and better captured local gradients in climate and productivity. The calibrated parameter ensemble was used to produce spatially continuous, high-resolution (10 m2) estimates of stocks and associated uncertainties of litter, microbial biomass, particulate, and protected SOC pools across the complex landscape. Subsequent projections of SOC response to idealized environmental disturbances illustrate the spatial complexity of potential SOC vulnerabilities across the watershed. Parametric uncertainty generated physicochemically protected soil C stocks that varied by a mean factor of 4.4 × across individual locations in the watershed and a − 14.9 to + 20.4% range in potential SOC stock response to idealized disturbances, illustrating the need for additional measurements of soil carbon fractions and their turnover time to improve confidence in the MIMICS simulations of SOC dynamics.
Baseline conditions and nutritional state upon hospitalization are the greatest risks for mortality for cardiovascular diseases and for several classes of diseases: a retrospective study
Authors: Loreggian Lara , Giorgini Filippo , Zakaria Ahmed S. , Fanchini Marco , Veronelli Annamaria , Pontiroli Antonio E. , Tagliabue Elena 
Published: June 2022

AbstractThe aim of this retrospective study was to evaluate risk factors for 3-years mortality after hospital discharge in all inpatients admitted to a general hospital in Milano, Italy. A total of 2580 consecutive patients admitted to Ospedale San Paolo, July 1 to December 31, 2012, for several classes of diseases (internal medicine, cancer, infectious diseases, trauma and surgery, pneumonia, and heart diseases) were studied. Age, total disease, type of admission, length of admission, age-adjusted Charlson index, prognostic nutritional index (PNI), and full blood count were evaluated. Univariate Cox models were used to evaluate the association between variables and death. Of the 2580 consecutive patients (age 66.8 ± 19.36 years, mean ± SD), 920 died within 3 years after discharge. At univariate analysis, all investigated variables, except sex and lymphocytes, were associated with patient death. Stepwise regression analyses revealed that the age-adjusted Charlson index or age plus total diseases, type of admission, number of admissions, and PNI were significant risk factors in the whole sample and in some classes of disease. Results were superimposable when considering death from date of admission instead of date of discharge, meaning that in-hospital death was not relevant to the total death count (115 out of 902). Seriousness of baseline conditions represents the major risk factor for mortality in most classes of disease, and possibly influences other predictors, such as type of admission and length of stay. This suggests that the current model of hospital admission might be improved, for instance, through comprehensive care at home, instead of hospital admission, or before admission.
The first long-read nuclear genome assembly of Oryza australiensis, a wild rice from northern Australia
Authors: Phillips Aaron L. , Ferguson Scott , Watson-Haigh Nathan S. , Jones Ashley W. , Borevitz Justin O. , Burton Rachel A. , Atwell Brian J. 
Published: June 2022

AbstractOryza australiensisis a wild rice native to monsoonal northern Australia. The InternationalOryzaMap Alignment Project emphasises its significance as the sole representative of the EE genome clade. Assembly of theO. australiensisgenome has previously been challenging due to its high Long Terminal Repeat (LTR) retrotransposon (RT) content. Oxford Nanopore long reads were combined with Illumina short reads to generate a high-quality ~ 858 Mbp genome assembly within 850 contigs with 46× long read coverage. Reference-guided scaffolding increased genome contiguity, placing 88.2% of contigs into 12 pseudomolecules. After alignment to theOryza sativacv. Nipponbare genome, we observed several structural variations. PacBio Iso-Seq data were generated for five distinct tissues to improve the functional annotation of 34,587 protein-coding genes and 42,329 transcripts. We also report SNV numbers for three additionalO. australiensisgenotypes based on Illumina re-sequencing. Although genetic similarity reflected geographical separation, the density of SNVs also correlated with our previous report on variations in salinity tolerance. This genome re-confirms the genetic remoteness of theO. australiensislineage within theO. officinalisgenome complex. Assembly of a high-quality genome forO. australiensisprovides an important resource for the discovery of critical genes involved in development and stress tolerance.