bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying SARS-CoV-2 regional introductions and transmission clusters in real time
Authors: McBroome Jakob , Martin Jennifer , de Bernardi Schneider Adriano , Turakhia Yatish , Corbett-Detig Russell 
Published: January 2022

AbstractThe unprecedented SARS-CoV-2 global sequencing effort has suffered from an analytical bottleneck. Many existing methods for phylogenetic analysis are designed for sparse, static datasets and are too computationally expensive to apply to densely sampled, rapidly expanding datasets when results are needed immediately to inform public health action. For example, public health is often concerned with identifying clusters of closely related samples, but the sheer scale of the data prevents manual inspection and the current computational models are often too expensive in time and resources. Even when results are available, intuitive data exploration tools are of critical importance to effective public health interpretation and action. To help address this need, we present a phylogenetic summary statistic which quickly and efficiently identifies newly introduced strains in a region, resulting clusters of infected individuals, and their putative geographic origins. We show that this approach performs well on simulated data and is congruent with a more sophisticated analysis performed during the pandemic. We also introduce Cluster Tracker (https://clustertracker.gi.ucsc.edu/), a novel interactive web-based tool to facilitate effective and intuitive SARS-CoV-2 geographic data exploration and visualization. Cluster-Tracker is updated daily and automatically identifies and highlights groups of closely related SARS-CoV-2 infections resulting from inter-regional transmission across the United States, streamlining public health tracking of local viral diversity and emerging infection clusters. The combination of these open-source tools will empower detailed investigations of the geographic origins and spread of SARS-CoV-2 and other densely-sampled pathogens.
Effectiveness of mRNA-1273 against SARS-CoV-2 omicron and delta variants
Authors: Tseng Hung Fu , Ackerson Bradley K. , Luo Yi , Sy Lina S. , Talarico Carla A. , Tian Yun , Bruxvoort Katia J. , Tubert Julia E. , Florea Ana , Ku Jennifer H. , Lee Gina S. , Choi Soon Kyu , Takhar Harpreet S. , Aragones Michael , Qian Lei 
Published: January 2022

AbstractSARS-CoV-2 omicron (B.1.1.529) variant is highly transmissible with potential immune escape. We conducted a test-negative case-control study to evaluate mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with omicron or delta. The large, diverse study population included 26,683 SARS-CoV-2 test-positive cases with variant determined by spike gene status (16% delta, 84% omicron). The 2-dose VE against omicron infection at 14-90 days was 44.0% (95% CI, 35.1–51.6%) but declined quickly. The 3-dose VE was 93.7% (92.2–94.9%) and 86.0% (78.1–91.1%) against delta infection and 71.6% (69.7–73.4%) and 47.4% (40.5–53.5%) against omicron infection at 14-60 days and >60 days, respectively. The 3-dose VE was 29.4% (0.3–50.0%) against omicron infection in immunocompromised individuals. The 3-dose VE against hospitalization with delta or omicron was >99%. Our findings demonstrate high, durable 3-dose VE against delta infection but lower effectiveness against omicron infection, particularly among immunocompromised people. However, 3-dose VE was high against hospitalization with delta or omicron.
Frequency Effects on Spelling Error Recognition: An ERP Study
Authors: Larionova Ekaterina V. , Martynova Olga V. 
Published: January 2022

AbstractSpelling errors are ubiquitous in all writing systems. Most studies exploring spelling errors focused on the phonological plausibility of errors. However, unlike typical pseudohomophones, spelling errors occur in naturally produced written language with variable frequencies. We investigated the time course of recognition of the most frequent orthographic errors in Russian (error in an unstressed vowel at the root) and the effect of word frequency on this process. During ERP recording, 26 native Russian speakers silently read high-frequency correctly spelled words, low-frequency correctly spelled words, high-frequency words with errors, and low-frequency words with errors. The amplitude of P200 was more positive for correctly spelled words than for misspelled words and did not depend on the frequency of the words. Word frequency affected spelling recognition in the later stages of word processing (350–700 ms): high-frequency misspelled words elicited a greater P300 than high-frequency correctly spelled words, and low-frequency misspelled words elicited a greater N400 than low-frequency correctly spelled words. We observe spelling effects in the same time window for both the P300 and N400, which may reflect temporal overlap between mainly categorization processes based on orthographic properties for high-frequency words and phonological processes for low-frequency words. We concluded that two independent pathways can be active simultaneously during spelling recognition: one reflects mainly orthographic processing of high-frequency words and the other is the phonological processing of low-frequency words. Our findings suggest that these pathways are associated with different ERP components. Therefore, our results complement existing reading models and demonstrate that the neuronal underpinnings of spelling error recognition during reading depend on word frequency.
Ecological speciation promoted by divergent regulation of functional genes within African cichlid fishes
Authors: Carruthers Madeleine , Edgley Duncan E. , Saxon Andrew D. , Gabagambi Nestory P. , Shechonge Asilatu , Miska Eric A. , Durbin Richard , Bridle Jon R. , Turner George F. , Genner Martin J. 
Published: January 2022

AbstractRapid ecological speciation along depth gradients has taken place independently and repeatedly in freshwater fishes. While the extent of genomic divergence between ecomorphs is often well understood, the molecular mechanisms facilitating such rapid diversification are typically unclear. In Lake Masoko, an East African crater lake, the cichlidAstatotilapia callipterahas diverged into shallow littoral and deep benthic ecomorphs with strikingly different jaw structures within the last 1,000 years. Using genome-wide transcriptome data from jaw tissue, we explore two major regulatory transcriptional mechanisms, expression and splicing QTL variants and examine their contribution to differential gene expression underpinning functional phenotypes. We identified 7,550 genes with significant differential expression between ecomorphs, of which 4.2% were regulated bycis-regulatory expression QTLs, and 6.4% were regulated bycis-regulatory splicing QTLs. There were also strong signals of divergent selection of differentially expressed genes that showed divergent regulation from expression, splicing or both QTL variants, including genes associated with major jaw plasticity and adaptation networks, adaptive immune system response, and oxidoreductase processes. These results suggest that transcriptome plasticity and modification have important roles during early-stage ecological speciation and demonstrate the role of regulatory-variants as important targets of selection driving ecologically-relevant divergence in gene expression that is associated with adaptive diversification.
Ecology, more than antibiotics consumption, is the major predictor for the global distribution of aminoglycoside-modifying enzymes
Authors: Pradier Léa , Bedhomme Stéphanie 
Published: January 2022

AbstractAntibiotics consumption and its abuses have been historically and repeatedly pointed out as the major driver of antibiotic resistance emergence and propagation. However, several examples show that resistance may persist despite substantial reductions in antibiotic use, and that other factors are at stake. Here we study the temporal, spatial, and ecological distribution patterns of aminoglycoside resistance, by screening more than 160,000 publicly available genomes for 27 clusters of genes encoding aminoglycoside-modifying enzymes (AMEGs). We find that AMEGs are ubiquitous: about 25% of sequenced bacteria carry AMEGs. These bacteria were sequenced from all the continents and terrestrial biomes, and belong to a wide number of phyla. By focusing on several European countries between 1997 and 2018, we show that aminoglycoside consumption has little impact on the prevalence of AMEG-carrying bacteria, whereas most variation in prevalence is observed among biomes. We further analyze the resemblance of resistome compositions across biomes: soil, wildlife, and human samples appear to be central to understand the exchanges of AMEGs between different ecological contexts. Moreover, the genomic distribution of AMEGs suggests a selection for widening resistance spectra, mostly driven by mobile genetic elements. Together, these results support the idea that interventional strategies based on reducing antibiotic use should be complemented by a stronger control of exchanges, especially between ecosystems.
Transcription shapes 3D chromatin organization by interacting with loop extrusion
Authors: Banigan Edward J. , Tang Wen , van den Berg Aafke A. , Stocsits Roman R. , Wutz Gordana , Brandão Hugo B. , Busslinger Georg A. , Peters Jan-Michael , Mirny Leonid A. 
Published: January 2022

AbstractCohesin folds mammalian interphase chromosomes by extruding the chromatin fiber into numerous loops. “Loop extrusion” can be impeded by chromatin-bound factors, such as CTCF, which generates characteristic and functional chromatin organization patterns. It has been proposed that transcription relocalizes or interferes with cohesin, and that active promoters are cohesin loading sites. However, the effects of transcription on cohesin have not been reconciled with observations of active extrusion by cohesin. To determine how transcription modulates extrusion, we studied mouse cells in which we could alter cohesin abundance, dynamics, and localization by genetic ‘knockouts’ of the cohesin regulators CTCF and Wapl. Through Hi-C experiments, we discovered intricate, cohesin-dependent contact patterns near active genes. Chromatin organization around active genes exhibited hallmarks of interactions between transcribing RNA polymerases (RNAPs) and extruding cohesins. These observations could be reproduced by polymer simulations in which RNAPs were “moving barriers” to extrusion that obstructed, slowed, and pushed cohesins. The simulations predicted that preferential loading of cohesin at promoters is inconsistent with our experimental data. Additional ChIP-seq experiments showed that the putative cohesin loader Nipbl is not predominantly enriched at promoters. Therefore, we propose that cohesin is not preferentially loaded at promoters and that the barrier function of RNAP accounts for cohesin accumulation at active promoters. Altogether, we find that RNAP is a new type of extrusion barrier that is not stationary, but rather, translocates and relocalizes cohesin. Loop extrusion and transcription might interact to dynamically generate and maintain gene interactions with regulatory elements and shape functional genomic organization.Significance StatementLoop extrusion by cohesin is critical to folding the mammalian genome into loops. Extrusion can be halted by CTCF proteins bound at specific genomic loci, which generates chromosomal domains and can regulate gene expression. However, the process of transcription itself can modulate cohesin, thus refolding chromosomes near active genes. Through experiments and simulations, we show that transcribing RNA polymerases (RNAPs) act as “moving barriers” to loop-extruding cohesins. Unlike stationary CTCF barriers, RNAPs actively relocalize cohesins, which generates characteristic patterns of spatial organization around active genes. Our model predicts that the barrier function of RNAP can explain why cohesin accumulates at active promoters and provides a mechanism for clustering active promoters. Through transcription-extrusion interactions, cells might dynamically regulate functional genomic contacts.
Wnt11 family dependent morphogenesis during frog gastrulation is marked by the cleavage furrow protein anillin
Authors: Van Itallie Elizabeth S. , Field Christine M. , Mitchison Timothy J. , Kirschner Marc W. 
Published: January 2022

AbstractWnt11 family proteins are ligands that activate a type of Dishevelled-mediated, non-canonical Wnt signaling pathway. Loss of function causes defects in gastrulation and/or anterior-posterior axis extension in all vertebrates. Non-mammalian vertebrate genomes encode two Wnt11 family proteins whose distinct functions have been unclear. We knocked down zygotic Wnt11b and Wnt11, separately and together, in Xenopus laevis. Single morphants exhibited very similar phenotypes of delayed blastopore closure, but they had different phenotypes at the tailbud stage. In response to their very similar gastrulation phenotypes, we chose to characterize dual morphants. Using dark field illuminated time-lapse imaging and kymograph analysis, we identified a failure of dorsal blastopore lip maturation that correlated with slower blastopore closure and failure to internalize the endoderm at the dorsal blastopore lip. We connected these externally visible phenotypes to cellular events in the internal tissues – including the archenteron – by imaging intact embryos stained for anillin and microtubules. The cleavage furrow protein anillin provided an exceptional cytological marker for blastopore lip and archenteron morphogenesis and the consequent disruption through loss of Wnt 11 signaling. These cytological changes suggest a novel role for the regulation of contractility and stiffness of the epithelial cells that result in dramatic shape changes and are important in gastrulation.
Toxin-producing endosymbionts shield pathogenic fungus against micropredators
Authors: Richter Ingrid , Radosa Silvia , Cseresnyés Zoltán , Ferling Iuliia , Büttner Hannah , Niehs Sarah P. , Gerst Ruman , Figge Marc Thilo , Hillmann Falk , Hertweck Christian 
Published: January 2022

AbstractThe phytopathogenic fungus Rhizopus microsporus harbours a bacterial endosymbiont (Mycetohabitans rhizoxinica) for the production of the toxin rhizoxin, the causative agent of rice seedling blight. This toxinogenic bacterial-fungal alliance is, however, not restricted to the plant disease, but has been detected in numerous environmental isolates from geographically distinct sites covering all five continents. Yet, the ecological role of rhizoxin beyond rice seedling blight has been unknown.Here we show that rhizoxin serves the fungal host in fending off protozoan and metazoan predators. Fluorescence microscopy and co-culture experiments with the fungivorous amoeba Protostelium aurantium revealed that ingestion of R. microsporus spores is toxic to P. aurantium. This amoebicidal effect is caused by the bacterial rhizoxin congener rhizoxin S2, which is also lethal towards the model nematode Caenorhabditis elegans. By combining stereomicroscopy, automated image analyses, and quantification of nematode movement we show that the fungivorous nematode Aphelenchus avenae actively feeds on R. microsporus that is lacking endosymbionts, while worms co-incubated with symbiotic R. microsporus are significantly less lively.This work uncovers an unexpected ecological role of rhizoxin as shield against micropredators. This finding suggests that predators may function an evolutionary driving force to maintain toxin-producing endosymbionts in non-pathogenic fungi.
Structure of the human inner kinetochore bound to a centromeric CENP-A nucleosome
Authors: Yatskevich Stanislau , Muir Kyle W. , Bellini Dom , Zhang Ziguo , Yang Jing , Tischer Thomas , Predin Masa , Dendooven Tom , McLaughlin Stephen H. , Barford David 
Published: January 2022

AbstractAccurate chromosome segregation, controlled by kinetochore-mediated chromatid attachments to the mitotic spindle, ensures the faithful inheritance of genetic information. Kinetochores assemble onto specialized CENP-A nucleosomes (CENP-ANuc) of centromeric chromatin. In humans, this is mostly organized as thousands of copies of an ∼171 bpα-satellite repeat. Here, we describe the cryo-EM structure of the human inner kinetochore CCAN (Constitutive Centromere Associated Network) complex bound to CENP-ANucreconstituted onto α-satellite DNA. CCAN forms edge-on contacts with CENP-ANuc, while a linker DNA segment of the α-satellite repeat emerges from the fully-wrapped end of the nucleosome to thread through the central CENP-LN channel which tightly grips the DNA. The CENP-TWSX histone-fold module, together with CENP-HIKHead, further augments DNA binding and partially wraps the linker DNA in a manner reminiscent of canonical nucleosomes. Our study suggests that the topological entrapment of theα-satellite repeat linker DNA by CCAN provides a robust mechanism by which the kinetochore withstands the pushing and pulling of centromeres associated with chromosome congression and segregation forces.One-Sentence SummaryThe human inner kinetochore CCAN complex tightly grips the linker DNA of the α-satellite CENP-A nucleosome.
The scaffolding protein Flot2 regulates cytoneme-based transport of Wnt3 in gastric cancer
Authors: Routledge Daniel , Rogers Sally , Ashktorab Hassan , Phesse Toby J , Scholpp Steffen 
Published: January 2022

AbstractThe Wnt/β-catenin signalling pathway regulates multiple cellular processes during development and many diseases, including cell proliferation, migration, and differentiation. Despite their hydrophobic nature, Wnt proteins exert their function over long distances to induce paracrine signalling. Recent studies have identified several factors involved in Wnt secretion, however, our understanding of how Wnt ligands are transported between cells to interact with their cognate receptors is still debated. Here, we demonstrate that gastric cancer cells utilise cytonemes to transport Wnt3 intercellularly to promote proliferation. Furthermore, we identify the membrane-bound scaffolding protein Flotillin-2 (Flot2), frequently overexpressed in gastric cancer, as a regulator of these cytonemes. Together with the Wnt co-receptor and cytoneme initiator Ror2, Flot2 determines the number and length of Wnt3 cytonemes in gastric cancer. Finally, we show that Flot2 is necessary for Wnt8a cytonemes during zebrafish embryogenesis, suggesting a conserved mechanism for Flot2-mediated Wnt transport on cytonemes in development and disease.
Adaptation and validation of a scale to evaluate the quality of virtual courses developed for medical students in Peru during the COVID-19 pandemic
Authors: Intimayta-Escalante Claudio , Plasencia-Dueñas Rubí , Flores-Lovon Kevin , Nuñez-Lupaca Janeth N. , Chavez-Hermosilla Mario , Castillo-Blanco Ronald 
Published: January 2022

AbstractBackgroundDuring the COVID-19 pandemic, medical education migrated to digital environments, without clear guidelines for virtual courses or evaluations of how these courses have been developed.ObjectiveTo adapt and validate a scale to evaluate the quality of virtual courses developed for human medicine students in Peru.MethodsCross-sectional study that adapted a scale to assess the quality of virtual courses to the context of Peruvian medical students during the COVID-19 pandemic, using the Delphi methodology and pilot tests for a rigorous evaluation of the items, resulting in a scale of 30 items that were described with summary statistics. In addition to the exploratory factor analysis (EFA) with Oblimin rotation, together with the adequacy and sample fit with Bartlett test and Kaiser-Meyer-Olkin (KMO), while the internal consistency was estimated with the alpha coefficient.ResultsA total of 297 medical students in Peru were surveyed. The descriptive statistics for the items showed a normal distribution, while the Bartlett test showed no inadequacy (X2=6134.34, p<0.01) and with the KMO test an overall value greater than 0.92 was found, therefore an AFE was performed where five factors were identified (General Quality and Didactic Methodology, Design and Navigation of the Virtual Platform, Multimedia Resources, Academic Materials) with 30 items. In the internal consistency, an alpha coefficient greater than 0.85 was estimated for the factors evaluated.ConclusionsThe adapted scale of 30 items grouped into five factors or domains, show adequate evidence of validity and reliability to be used in the evaluation of the quality of virtual courses developed for Peruvian human medicine students during the context of the COVID-19 pandemic.
The Challenges for Screening and Diagnosing Gestational Diabetes Mellitus in Brazil: a cross-sectional study in a low-risk obstetric hospital
Authors: Paes Maria Bruna Marcolino , Fernandes Vivaldo Debora Giovanna , Izidoro Thais Sales , De Freitas Ana Paula Costa , Takano Luiz , Caldeirao Talita Domingues , Sartorao Filho Carlos Izaias 
Published: January 2022

BackgroundGestational Diabetes Mellitus (GDM) is a very prevalent disease and can cause several morbidities for women and their offspring. The literature demonstrates the necessity for a better approach during prenatal assistance to detect and treat the disease. We aimed to evaluate the model and efficacy of GDM screening and diagnosis in a referenced low-risk obstetrical center of the municipality of Assis, Sao Paulo state, Brazil. Moreover, the specific objective was to evaluate the prevalence of GDM.MethodsWe conducted a retrospective cross-sectional study of pregnant women, in which 257 prenatal cards and the clinical approaches used for GDM diagnosis and their results. We observed the consecutive patients admitted to the low-risk referenced obstetrical service of the “Santa Casa de Assis-SP” for childbirth from January to August 2021.ResultsThere were 257 pregnant women, 227 prenatal cards obtained. Of these, 24.6% of the cards were considered incomplete, 25 (9.72%) did not contain the initial fasting plasma glucose information, and 93 (36.18%) did not describe this information in the second to the third trimester. The prevalence of GDM in the population was 14.78%.ConclusionWe observed many pregnant women not screened according to the recommended guidelines and many prenatal cards with incomplete information. According to the screening and diagnosis guidelines, GDM prevalence was underestimated. The lack of prenatal card information and inadequacy of screening and diagnoses were observed in this population.