bluuebunny/crossref_metadata_2025_split huggingface dataset:
MGTdb: A web service and database for studying the global and local genomic epidemiology of bacterial pathogens
Authors: Kaur Sandeep , Payne Michael , Luo Lijuan , Octavia Sophie , Tanaka Mark M. , Sintchenko Vitali , Lan Ruiting 
Published: June 2022

AbstractMultilevel genome typing (MGT) enables the genomic characterization of bacterial isolates and the relationships among them. The MGT system describes an isolate using multiple multilocus sequence typing (MLST) schemes, referred to as levels. Thus, for a new isolate, sequence types (STs) assigned at multiple precisely defined levels can be used to type isolates at multiple resolutions. The MGT designation for isolates is stable, and assignment is faster than existing approaches. MGT’s utility has been demonstrated in multiple species.This paper presents a publicly accessible web service called MGTdb, which enables the assignment of MGT sequence types to isolates, along with their storage, retrieval and analysis. The MGTdb web service enables upload of genome data as sequence reads or alleles, which are processed and assigned MGT identifiers. Additionally, any newly sequenced isolates deposited in NCBI Sequence Read Archive are also regularly retrieved (currently daily), processed, assigned MGT and made publicly available in MGTdb. Interactive visualisation tools are presented to assist analysis, along with capabilities to download publicly available isolates and assignments for use with external software.MGTdb is currently available for Salmonella enterica serovars Typhimurium and Enteritidis, and Vibrio cholerae. We demonstrate the usability of MGTdb through three case studies to study the long-term national surveillance of S. Typhimurium, and the local epidemiology and outbreaks of S. Typhimurium, and the global epidemiology of V. cholerae. Thus, MGTdb enables epidemiological and microbiological investigations at multiple levels of resolution for all publicly available isolates of these pathogens.Database URLhttps://mgtdb.unsw.edu.au
Isolation-by-distance and population-size history inferences from the coho salmon (Oncorhynchus kisutch) genome
Authors: Rondeau Eric B. , Christensen Kris A. , Minkley David R. , Leong Jong S. , Chan Michelle T.T. , Despins Cody A. , Mueller Anita , Sakhrani Dionne , Biagi Carlo A. , Rougemont Quentin , Normandeau Eric , Jones Steven J.M. , Devlin Robert H. , Withler Ruth E. , Beacham Terry D. , Naish Kerry A. , Yáñez José M. , Neira Roberto , Bernatchez Louis , Davidson William S. , Koop Ben F. 
Published: June 2022

AbstractCoho salmon (Oncorhynchus kisutch) are a culturally and economically important species that return from multiyear ocean migrations to spawn in rivers that flow to the Northern Pacific Ocean. Southern stocks of coho salmon have significantly declined over the past quarter century, and unfortunately, conservation efforts have not reversed this trend. To assist in stock management and conservation efforts, we generated two chromosome-level genome assemblies and sequenced 24 RNA-seq libraries to better annotate the coho salmon genome assemblies. We also resequenced the genomes of 83 coho salmon across their North American range to identify nucleotide variants, characterize the broad effects of isolation-by-distance using a genome-wide association analysis approach, and understand the demographic histories of these salmon by modeling population size from genome-wide data. We observed that more than 13% of all SNPs were associated with latitude (before multiple test correction), likely an affect of isolation-by-distance. From demographic history modeling, we estimated that the SNP latitudinal gradient likely developed as recently as 8,000 years ago. In addition, we identified four genes each harboring multiple SNPs associated with latitude; all of these SNPs were also predicted to modify the function of the gene. Three of these genes have roles in cell junction maintenance and may be involved in osmoregulation. This signifies that ocean salinity may have been a factor influencing coho salmon recolonization after the last glaciation period – generating the current pattern of variation in these three genes.
Inhibition of Fas Receptor Endocytosis Sensitizes Cancer Cells to Fas-induced Apoptosis
Authors: Kural Mehmet H. , Djakbarova Umidahan , Cakir Bilal , Tanaka Yoshiaki , Madraki Yasaman , Qian Hong , Park Jinkyu , Sewanan Lorenzo R. , Kural Comert , Niklason Laura E. 
Published: June 2022

AbstractFas (CD95/APO-1) is a transmembrane death receptor that transduces apoptotic signals upon binding to its ligand and assembling into a death-inducing signaling complex (DISC) (1, 2). Intracellular trafficking of Fas receptors, including recycling from endosomes to the plasma membrane, plays a vital role in ligand-induced assembly of DISC (3, 4). Although Fas is highly expressed in tumor cells (5, 6), insufficient expression of these receptors on the cell surface makes cancer cells insensitive to the Fas-induced apoptosis (4, 7–9). Here we show that inhibition of endocytosis increases the formation of Fas microaggregates on the plasma membrane and sensitizes cancer cells to Fas-induced apoptosis. We have identified a clinically used vasodilator, Fasudil, that slows down endocytosis by increasing plasma membrane tension. Fasudil enhanced apoptosis in cancerous cells when combined with exogenous soluble Fas ligand (FasL), whereas the synergistic effect was substantially weaker in nonmalignant cells. Additionally, the FasL and Fasudil combination prevented glioblastoma cell growth in embryonic stem cell-derived brain organoids and induced tumor regression in a xenograft U87 tumor model in nude mice. Our results demonstrate that FasL treatment has strong potential as an apoptosis-directed cancer therapy when the formation of Fas microaggregates is augmented by slowing down endocytosis dynamics.
In colon cancer cells, fascin1 functions as a mechanosensor that transforms adherens junction mechanotransduction
Authors: Esmaeilniakooshkghazi Amin , Pham Eric , George Sudeep P. , Ahrorov Afzal , Villagomez Fabian R. , Byington Michael , Mukhopadhyay Srijita , Patnaik Srinivas , Conrad Jacinta C. , Naik Monali , Ravi Saathvika , Tebbuttt Niall , Mooi Jennifer , Reehorst Camilla M , Mariadason John M. , Khurana Seema 
Published: June 2022

SummaryFascin1 expression in colorectal carcinomas (CRCs) is linked to a clinically aggressive disease with poor prognosis. Despite that fascin1’s role in the etiology of CRCs has not been directly investigated. We show fascin1 expression in one-third of all CRCs underscoring the critical need to identify fascin1’s function in colorectal carcinogenesis. Here, we identify for the first time, fascin1’s role as a mechanosensor that modulates CRC cell adherens junction (AJ) plasticity to induce tumor growth and metastasis. We show that fascin1 expression drives protein sorting to transform AJ mechanotransduction and we reveal how these force-sensitive pathways activate oncogenic signaling in CRC cells. We made the novel finding that AJ remodeling by fascin1 also controls “collective plasticity” and bidirectional cell migration. Few studies have examined AJ plasticity in cancer cells, which remains poorly understood and has not been therapeutically targeted. Our findings could have widespread implications for understanding and treating metastatic carcinomas.
Influencing Factors for the Persistence of SARS-Cov-2 (Covid-19) exposed in Environmental Matrices and Disinfection Methods: Systematic Review
Authors: Yu Chaw Chaw , Hlaing Thein , Tun Kyaw Myo 
Published: June 2022

AbstractBackgroundSince the COVID-19 pandemic has been pestilential over a considerable duration, global deployment and financial crisis could not be reversed as before. It brought up essentials to allow the nations back to work with effective preventive measures. This review intended to evaluate the persistence of SARS-CoV-2(COVID-19) exposed in the environmental matrices, influencing factors on the virus persistence and disinfection methods.MethodsApplying the PRISMA 2020 tool, MEDLINE/PubMed, HINARI, and Google Scholar were primarily explored. Data were extracted, entered into the modified data extraction forms and analysed narratively. Quality appraisal was done by the Mixed-Methods Appraisal Tool. The findings were presented descriptively.ResultsPersistence of SARS-CoV-2 was revealed <4 hours on aluminium, 4 hours on copper, 24 hours on cardboard, 44 hours on glass, 48 hours on stainless steel, 72 hours on plastic, 92 hours on polystyrene plastic, 1.1-1.2 hours in the air, 7 days (higher titer) to 3 days(lower titer) in wastewater. Virus decaying was noted 5-10 times faster at 27°C than at 10°C and 2-5 times faster with 65% relative humidity (RH) than with 40% and 100% RH. Virus infectivity was reduced by far-UVC-(222 nm) light for 90%-(8 minutes), 95%-(11 minutes), 99%-(16 minutes) and 99.99%-(25 minutes). Sodium hypochlorite (800 g/m3) and ammonium-based detergents were remarkably effective for preliminary disinfection.ConclusionsThis review identified the duration of SARS-CoV-2 survival in environmental matrices for both healthcare and non-healthcare settings. The study explored the impacts of environmental factors on the virus and effective disinfection methods to be considered accordingly to the findings.
How acceptable is rapid whole genome sequencing for infectious disease management in hospitals? Perspectives of those involved in managing nosocomial SARS-CoV-2
Authors: Flowers Paul , McLeod Julie , Mapp Fiona , Stirrup Oliver , Blackstone James , Snell Luke B , Peters Christine , Thomson Emma , Holmes Alison , Price James , Partridge Dave , Shallcross Laura , de Silva Thushan I , Breuer Judith 
Published: June 2022

Structured summaryBackgroundWhole genome sequencing (WGS) for managing healthcare associated infections (HCAIs) has developed considerably through experiences with SARS-CoV-2. We interviewed various healthcare professionals (HCPs) with direct experience of using WGS in hospitals (within the COG-UK Hospital Onset COVID-19 Infection (HOCI) study) to explore its acceptability and future use.MethodAn exploratory, cross-sectional, qualitative design employed semi-structured interviews with 39 diverse HCPs between December 2020 and June 2021. Participants were recruited from five sites within the larger clinical study of a novel genome sequencing reporting tool for SARS-CoV-2 (the HOCI study). All had experience, in their diverse roles, of using sequencing data to manage nosocomial SARS-CoV-2 infection. Deductive and inductive thematic analysis identified themes exploring aspects of the acceptability of sequencing.FindingsThe analysis highlighted the overall acceptability of rapid WGS for infectious disease using SARS-CoV-2 as a case study. Diverse professionals were largely very positive about its future use and believed that it could become a valuable and routine tool for managing HCAIs. We identified three key themes ‘1) ‘Proof of concept achieved’; 2) ‘Novel insights and implications’; and 3) ‘Challenges and demands’.ConclusionOur qualitative analysis, drawn from five diverse hospitals, shows the broad acceptability of rapid sequencing and its potential. Participants believed it could and should become an everyday technology capable of being embedded within typical hospital processes and systems. However, its future integration into existing healthcare systems will not be without challenges (e.g., resource, multi-level change) warranting further mixed methods research.
The influence of place on COVID-19 vaccine coverage in Alberta: A multilevel analysis
Authors: Paudel Yuba Raj , Du Crystal , MacDonald Shannon E. 
Published: June 2022

AbstractBackgroundWhile there is evidence of urban/rural disparities in COVID-19 vaccination coverage, there is limited data on the influence of other place-based variables.MethodsIn this cross-sectional study, we analyzed population-based linked administrative health data to examine vaccination coverage for 3,945,103 residents in Alberta, Canada. We used multilevel logistic regression to examine the association of vaccination coverage with various place-based variables.ResultsAfter 4 months of widely available COVID-19 vaccine, coverage varied widely between rural and urban areas (58% to 73%) and between geographic health authority zones (55.8% to 72.8%). Residents living in neighborhoods with lower COVID-19 disease incidence had the lowest vaccination coverage (63.2%), while coverage in higher incidence neighborhoods ranged from 68.3% to 71.9%. The multilevel logistic regression model indicated that residence in metro (adjusted odds ratio [aOR] 1.37; 95% CI: 1.31-1.42) and urban areas (aOR 1.11; 95% CI: 1.08-1.14) was associated with higher vaccine coverage than residence in rural areas. Similarly, residence in Edmonton, Calgary, and South health zones was associated with higher vaccine coverage compared to residence in Central zone. Higher income neighborhoods reported higher vaccine coverage than the lowest-income neighborhoods, and the highest COVID-19 risk neighborhoods reported higher vaccine coverage than the lowest risk neighborhoods (aOR 1.52; 95% CI: 1.12-2.05).ConclusionIn the first four months of wider vaccine availability in Alberta, COVID-19 vaccine coverage varied according to various place-based characteristics. Vaccine distribution strategies need to consider place-based variables for program prioritization and delivery.
A network of DZF proteins controls alternative splicing regulation and fidelity
Authors: Haque Nazmul , Will Alexander , Cook Atlanta G. , Hogg J. Robert 
Published: June 2022

AbstractProteins containing DZF (domain associated withzinc fingers) modules play important roles throughout gene expression, from transcription to translation. Derived from nucleotidyltransferases but lacking catalytic residues, DZF domains serve as heterodimerization surfaces between DZF protein pairs. Three DZF proteins are widely expressed in mammalian tissues, ILF2, ILF3, and ZFR, which form mutually exclusive ILF2-ILF3 and ILF2-ZFR heterodimers. Using eCLIP-Seq, we find that ZFR binds across broad intronic regions to regulate the alternative splicing of cassette and mutually exclusive exons. ZFR preferentially binds dsRNAin vitroand is enriched on introns containing conserved dsRNA elements in cells. Many splicing events are similarly altered upon depletion of any of the three DZF proteins; however, we also identify independent and opposing roles for ZFR and ILF3 in alternative splicing regulation. Along with widespread involvement in cassette exon splicing, the DZF proteins control the fidelity and regulation of over a dozen highly validated mutually exclusive splicing events. Our findings indicate that the DZF proteins form a complex regulatory network that leverages dsRNA binding by ILF3 and ZFR to modulate splicing regulation and fidelity.
AKT1-FOXO4 AXIS RECIPROACLLY REGULATES HEMOCHORIAL PLACENTATION
Authors: Kozai Keisuke , Moreno-Irusta Ayelen , Iqbal Khursheed , Winchester Mae-Lan , Scott Regan L. , Simon Mikaela E. , Muto Masanaga , Parrish Marc R. , Soares Michael J. 
Published: June 2022

ABSTRACTHemochorial placentation involves the differentiation of specialized cells called invasive trophoblast cells possessing the capacity to exit the placenta and invade into the uterus where they restructure the vasculature. Invasive trophoblast cells arise from a well-defined compartment within the placenta, referred to as the junctional zone in the rat and the extravillous trophoblast cell column in the human. In this study, we investigated roles for AKT1, a serine/threonine kinase, in placental development using a genome-edited/loss-of-function rat model. Disruption of AKT1 resulted in placental, fetal, and postnatal growth restriction. Forkhead box O4 (Foxo4), which encodes a transcription factor and known AKT substrate, was abundantly expressed in the junctional zone and invasive trophoblast cells of the rat placentation site.Foxo4gene disruption using genome-editing resulted in placentomegaly, including an enlarged junctional zone. AKT1 and FOXO4 regulate the expression of many of the same transcripts expressed by trophoblast cells; however, in opposite directions. In summary, we have identified AKT1 and FOXO4 as part of a regulatory network that reciprocally controls critical indices of hemochorial placenta development.SUMMARY STATEMENTGenome-edited rat models were utilized to investigate roles for AKT1 and FOXO4 in hemochorial placentation. AKT1 and FOXO4 possess reciprocal actions in regulating development of the hemochorial placenta.
Uncertainty quantification of reference based cellular deconvolution algorithms
Authors: Seiler Vellame Dorothea , Shireby Gemma , MacCalman Ailsa , Dempster Emma L , Burrage Joe , Gorrie-Stone Tyler , Schalkwyk Leonard S , Mill Jonathan , Hannon Eilis 
Published: June 2022

AbstractThe majority of epigenetic epidemiology studies to date have generated genome-wide profiles from bulk tissues (e.g. whole blood) however these are vulnerable to confounding from variation in cellular composition. Proxies for cellular composition can be mathematically derived from the bulk tissue profiles using a deconvolution algorithm however, there is no method to assess the validity of these estimates for a dataset where the true cellular proportions are unknown. In this study, we describe, validate and characterise a sample level accuracy metric for derived cellular heterogeneity variables. The CETYGO score captures the deviation between a sample’s DNAm profile and its expected profile given the estimated cellular proportions and cell type reference profiles.We demonstrate that the CETYGO score consistently distinguishes inaccurate and incomplete deconvolutions when applied to reconstructed whole blood profiles. By applying our novel metric to > 6,300 empirical whole blood profiles, we find that estimating accurate cellular composition is influenced by both technical and biological variation. In particular, we show that when using the standard reference panel for whole blood, less accurate estimates are generated for females, neonates, older individuals and smokers. Our results highlight the utility of a metric to assess the accuracy of cellular deconvolution, and describe how it can enhance studies of DNA methylation that are reliant on statistical proxies for cellular heterogeneity. To facilitate incorporating our methodology into existing pipelines, we have made it freely available as an R package (https://github.com/ds420/CETYGO).
Phase-Restoring Subpixel Image Registration: Enhancing Motion Detection Performance in Fourier-domain Optical Coherence Tomography
Authors: Li Huakun , Tan Bingyao , Pandiyan Vimal Prabhu , Barathi Veluchamy Amutha , Sabesan Ramkumar , Schmetterer Leopold , Ling Tong 
Published: June 2022

AbstractPhase-sensitive Fourier-domain optical coherence tomography (FD-OCT) enables in-vivo, label- free imaging of cellular movements with detection sensitivity down to the nanometer scale, and it is widely employed in emerging functional imaging modalities, such as optoretinography (ORG), Doppler OCT, and optical coherence elastography. However, when imaging tissue dynamics in vivo, tissue movement or bulk motion introduces decorrelation noise that compromises motion detection performance, particularly in terms of sensitivity and accuracy. Here, we demonstrate that the motion-related decorrelation noise in FD-OCT can be accurately corrected by restoring the initial sampling points using our proposed Phase-Restoring Subpixel Image Registration (PRESIR) method. Derived from a general FD-OCT model, the PRESIR method enables translational shifting of complex-valued OCT images over arbitrary displacements with subpixel precision, while accurately restoring phase components. Unlike conventional approaches that shift OCT images either in the spatial domain at the pixel level or in the spatial frequency domain for subpixel correction, our method reconstructs OCT images by correcting axial displacement in the spectral domain (k domain) and lateral displacement in the spatial frequency domain. We validated the PRESIR method through simulations, phantom experiments, and in-vivo optoretinography in both rodents and human subjects. Our approach significantly reduced decorrelation noise during the imaging of moving samples, achieving phase sensitivity close to the fundamental limit determined by the signal-to-noise ratio (SNR).
Single locus phosphoproteomics reveals phosphorylation of RPA-1 is required for generation of single-strand DNA following a break at a subtelomeric locus
Authors: McLaughlin Emilia , Dujeancourt-Henry Annick , Chaze Thibault , Gianetto Quentin Giai , Matondo Mariette , Urbaniak Michael D , Glover Lucy 
Published: June 2022

AbstractDamage to the genetic material of the cell poses a universal threat to all forms of life. Central to the DNA damage response (DDR) is a phosphorylation signalling cascade that leads to the co-ordination of the cellular response to a DNA break. Identifying the proteins that are phosphorylated is crucial to understanding the mechanisms underlying this DDR. We have used SILAC-based quantitative phosphoproteomics to profile changes in phosphorylation site abundance following a single double strand break (DSB) at a chromosome internal locus and the subtelomeric bloodstream form expression site in Trypanosoma brucei. We report >6500 phosphorylation sites, including a core set of 211 DSB responsive phosphorylation sites. Along with phosphorylation of canonical DNA damage factors, we find that there is a striking distinction between the proteins phosphorylated in response to a chromosome internal DSB and one at the active BES and describe a single phosphorylation event on Replication factor A (RPA) 1 that is required for efficient resection at a bloodstream form expression site.