bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 Vaccine Hesitancy among Marginalized Populations in the U.S. and Canada: Protocol for a Scoping Review
Authors: Newman Peter A. , Reid Luke , Tepjan Suchon , Fantus Sophia , Allan Kate , Nyoni Thabani , Guta Adrian , Williams Charmaine C. 
Published: March 2022

AbstractIntroductionDespite the development of safe and highly efficacious COVID-19 vaccines, extensive barriers to vaccine deployment and uptake threaten the effectiveness of vaccines in controlling the pandemic. Notably, marginalization produces structural and social inequalities that render certain populations disproportionately vulnerable to COVID-19 incidence, morbidity, and mortality, and less likely to be vaccinated. The purpose of this scoping review is to provide a comprehensive overview of definitions/conceptualizations, elements, and determinants of COVID-19 vaccine hesitancy among marginalized populations in the U.S. and Canada.Materials and MethodsThe proposed scoping review follows the framework outlined by Arksey and O’Malley, and further developed by the Joanna Briggs Institute. It will comply with reporting guidelines from the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The overall research question is: What are the definitions/conceptualizations and factors associated with vaccine hesitancy in the context of COVID-19 vaccines among adults from marginalized populations in the U.S. and Canada. Search strategies will be developed using controlled vocabulary and selected keywords, and customized for relevant databases, in collaboration with a research librarian. The results will be analyzed and synthesized quantitatively (i.e., frequencies) and qualitatively (i.e., thematic analysis) in relation to the research questions, guided by a revised WHO Vaccine Hesitancy Matrix.DiscussionThis scoping review will contribute to honing and advancing the conceptualization of COVID-19 vaccine hesitancy and broader elements and determinants of underutilization of COVID-19 vaccination among marginalized populations, identify evidence gaps, and support recommendations for research and practice moving forward.
Mutation-Attention (MuAt): deep representation learning of somatic mutations for tumour typing and subtyping
Authors: Sanjaya Prima , Waszak Sebastian M. , Stegle Oliver , Korbel Jan O. , Pitkänen Esa 
Published: March 2022

AbstractCancer genome sequencing enables accurate classification of tumours and tumour sub-types. However, prediction performance is still limited using exome-only sequencing and for tumor types with low somatic mutation burden such as many pediatric tumours. Moreover, the ability to leverage deep representation learning in discovery of tumour entities remains unknown. We introduce here Mutation-Attention (MuAt), a deep neural network to learn representations of simple and complex somatic alterations for prediction of tumour types and subtypes. MuAt achieved prediction accuracy of 89% for whole genomes (24 tumour types) and 64% for whole exomes (20 types), and a top-5 accuracy of 97% and 90%, respectively. Tumour representations learnt by MuAt included tumour entities such as acral melanoma, SHH-activated medulloblastoma, SPOP-associated prostate cancer, microsatellite instability, and MUTYH-associated pancreatic endocrine tumours although these tumour subtypes and subgroups were not used as training labels. Integrated representations of somatic alterations hold significant potential to drive discovery of novel tumour entities and clinical application.
Epistatic Modifiers Influence the Expression of Continual Flowering in Strawberry
Authors: Cockerton Helen Maria , Nellist Charlotte Florence , Hytönen Timo , Litthauer Suzanne , Hopson Katie , Whitehouse Adam , Sobczyk Maria , Harrison Richard Jonathan 
Published: March 2022

SummaryPrevious work within the community led to the identification of a single dominant allele that controls the everbearing trait. However, frequent observations have indicated that crosses do not segregate in a Mendelian fashion, as would be expected for a trait controlled by a single dominant gene. Therefore, it was hypothesised that one or more unidentified epistatic alleles interact with the major gene.A GWAS was conducted on 587 June-bearers and 207 everbearers to assess the genetic components associated with flowering habit. The segregation ratios of parental strawberry lines with known phenotypes were used to validate the identified alleles.Three loci including the known, major FaPFRU locus and two epistatic modifiers were identified. These modifiers function as enhancers of the everbearing trait in individuals containing a single copy of the FaPFRU everbearing allele and appear to be functionally redundant. Principally, heterozygous individuals required the presence of two modifying alleles in order to allow expression of the everbearing trait.Inclusion of the epistatic alleles improved the prediction of everbearing segregation ratios, beyond that of a single allele model, however, a large proportion of the variation remained unexplained. Future work should identify the additional repressor and enhancer modifiers not identified here. Discovering the genetic components controlling the everbearing trait can enable genetic informed strawberry improvement.Society Impact StatementUntil the 1970s, the majority of commercial strawberry varieties produced a single bloom of flowers. However, continuously flowering, everbearing strawberries are now routinely cultivated and use is increasing. Indeed, introgression of the everbearing flowering trait can lead to economic benefits for growers through the production of a continual crop from the same plant. Utilising genetic guided improvement has the power to streamline everbearing generation. As such, utilising the genetic markers reported here, can help to identify everbearing individuals at an early time point in the breeding process. Furthermore, these markers can help to improve the predictions of progeny segregation ratios.
Segregational instability of multicopy plasmids: a population genetics approach
Authors: Pina V Miró , Hernández JCR , Siri-Jégousse A , Peña-Miller R , Palau S , González Casanova A 
Published: March 2022

ABSTRACTPlasmids are extra-chromosomal genetic elements that encode a wide variety of phenotypes and can be maintained in bacterial populations through vertical and horizontal transmission, thus increasing bacterial adaptation to hostile environmental conditions like those imposed by antimicrobial sub-stances. To circumvent the segregational instability resulting from randomly distributing plasmids between daughter cells upon division, non-transmissible plasmids tend to be carried in multiple copies per cell, with the added benefit of exhibiting increased gene dosage and resistance levels. But carrying multiple copies also results in a high metabolic burden to the bacterial host, therefore reducing the overall fitness of the population. This trade-off poses an existential question for plasmids: What is the optimal plasmid copy number? In this manuscript, we address this question by postulating and analyzing a population genetics model to evaluate the interaction between selective pressure, the number of plasmid copies carried by each cell, and the metabolic burden associated with plasmid bearing in the absence of selection for plasmid-encoded traits. Parameter values of the model were estimated experimentally usingEscherichia coliK12 carrying a multicopy plasmid encoding for a fluorescent protein andblaTEM-1, a gene conferring resistance toβ-lactam antibiotics. By numerically determining the optimal plasmid copy number for constant and fluctuating selection regimes, we show that plasmid copy number is a highly optimized evolutionary trait that depends on the rate of environmental fluctuation and balances the benefit between increased stability in the absence of selection with the burden associated with carrying multiple copies of the plasmid.
Genome-wide binding of Multiple ankyrin repeats single KH domain reveals its role in maintenance of gene activation by trithorax group proteins in Drosophila
Authors: Shaukat Ammad , Khan Muhammad Haider Farooq , Akhtar Jawad , Bakhtiari Mahnoor Hussain , Haseeb Muhammad Abdul , Mazhar Khalida , Umer Zain , Tariq Muhammad 
Published: March 2022

AbstractThe Trithorax group (trxG) proteins counteract repressive effect of Polycomb group (PcG) complexes and maintain transcriptional memory of active states of key developmental genes. Although, chromatin structure and modifications appear to play a fundamental role in this process, it is not clear how trxG prevents PcG-silencing and heritably maintain an active gene expression state. Here, we report a hitherto unknown role of Drosophila Multiple ankyrin repeats single KH domain (Mask), which emerged as one of the candidate trxG genes in our reverse genetic screen. The genome-wide binding profile of Mask correlates with known trxG binding sites across Drosophila genome. In particular, association of Mask at chromatin overlaps with CBP and H3K27ac, which are known hallmarks of actively transcribed genes by trxG. Importantly, Mask predominantly associates with actively transcribed genes in Drosophila. Depletion of Mask not only results in downregulation of trxG targets but also correlates with drastic reduction in H3K27ac levels and an increased H3K27me3 levels. The fact that MASK positively regulates H3K27ac levels in flies was also found to be conserved in human cells. Finally, strong suppression of Pc mutant phenotype by mutation in mask provides physiological relevance that Mask contributes to the anti-silencing effect of trxG, maintaining expression of key developmental genes. Since Mask is a downstream effector of multiple cell signaling pathways, we propose that Mask may connect cell signaling with chromatin mediated epigenetic cell memory governed by trxG.
Uterine injury during diestrus leads to embryo spacing defects and perturbations in the COX pathway in subsequent pregnancies
Authors: Zhang Elisa T. , Wells Kristen L. , Steinmetz Lars , Baker Julie C. 
Published: March 2022

AbstractUterine injury from procedures such as Cesarean sections (C-sections) often have severe consequences on subsequent pregnancy outcomes, leading to disorders such as placenta previa, placenta accreta, and infertility. With rates of C-section at approximately 30% of deliveries in the US and that are projected to continue to climb, a deeper understanding of the mechanisms by which these pregnancy disorders arise and opportunities for intervention are needed. However, there are no animal models to date that comprehensively assess the consequences of uterine injury. Here we describe a rodent model of uterine injury on subsequent in utero outcomes. We observed three distinct phenotypes: increased rates of resorption and death, embryo spacing defects, and placenta accreta-like features of reduced decidua and expansion of invasive trophoblasts. We show that the appearance of embryo spacing defects depends entirely on the phase of estrous cycle at the time of injury. Using RNA-seq, we identified perturbations in the expression of components of the COX/prostaglandin pathway after recovery from injury, a pathway that has previously been demonstrated to play an important role in embryo spacing. Therefore, we demonstrate that uterine damage in this mouse model causes morphological and molecular changes, most notably perturbed expression of COX/prostaglandin pathway-related genes, that ultimately lead to placental and embryonic developmental defects.
Tales of Two α-Carboxysomes: the Structure and Assembly of Cargo Rubisco
Authors: Ni Tao , Sun Yaqi , Seaton-Burn William , Al-Hazeem Monsour M. J. , Zhu Yanan , Yu Xiulian , Liu Lu-Ning , Zhang Peijun 
Published: March 2022

AbstractCarboxysomes are a family of bacterial microcompartments in cyanobacteria and chemoautotrophs. It encapsulates carbonic anhydrase and Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalysing carbon fixation inside a proteinaceous shell. How Rubisco packs into the carboxysomes is unknown. Using cryo-electron tomography and subtomogram averaging, we present 3D organization of Rubisco inside two types of native α-carboxysomes from a marine α-cyanobacterium Cyanobium sp. PCC 7001 and a chemoautotrophic bacterium Halothiobacillus neapolitanus. We determined the structures of Rubiscos within native Halothiobacillus and Cyanobium carboxysomes at 3.3 Å and 3.8 Å resolution respectively and further identified an associated CsoS2 segment. Interestingly, CsoS2 is only associated with a sub-population of Rubiscos that are close to the shell in Halothiobacillus, but with all Rubiscos throughout Cyanobium carboxysome. Moreover, Rubiscos in Cyanobium carboxysomes are organized in three concentric layers whereas Rubiscos in Halothiobacillus carboxysomes are arranged in spiral arrays. Calcium treatment induced a drastic re-organization of Rubiscos, converting these two distinct assemblies into ordered lattice arrays in both α-carboxysomes. Our findings provide critical knowledge of the assembly principles of α-carboxysomes, which may aid in rational design and repurpose of carboxysome structures for new functions.
Validating methods to eradicate Select Agent and phylotype I Ralstonia solanacearum strains reveals that growth in planta increases bacterial stress tolerance
Authors: Hayes Madeline M. , Dewberry Ronnie J. , Babujee Lavanya , Moritz Rebecca , Allen Caitilyn 
Published: March 2022

AbstractRalstonia solanacearum is a destructive pathogen that causes bacterial wilt disease of diverse crops. Wilt disease prevention and management is difficult because R. solanacearum persists in soil, water, and plant material. Growers need practical methods to kill R. solanacearum in irrigation water, a common source of disease outbreaks. Additionally, the Race 3 biovar 2 (R3bv2) subgroup is a quarantine pest in many countries and a highly regulated U.S. Select Agent. Plant protection officials and researchers need validated protocols to eradicate R. solanacearum for regulatory compliance. To meet these needs, we measured survival of four R3bv2 and three phylotype I R. solanacearum strains following treatment with hydrogen peroxide, stabilized hydrogen peroxide (HuwaSan), active chlorine, heat, ultraviolet radiation, and desiccation. No surviving R. solanacearum cells were detected after cultured bacteria were exposed for ten minutes to 400 ppm hydrogen peroxide, 50 ppm HuwaSan, 50 ppm active chlorine, or temperatures above 50°C. R. solanacearum cells on agar plates were eradicated by 30s UV irradiation and killed by desiccation on most biotic and all abiotic surfaces tested. R. solanacearum did not survive the cell lysis steps of four nucleic acid extraction protocols. However, bacteria in planta were more difficult to kill. Stems of infected tomato plants contained a subpopulation of bacteria with increased tolerance of heat and UV light, but not oxidative stress. This result has significant management implications. We demonstrate the utility of these protocols for compliance with Select Agent research regulations and for management of a bacterial wilt outbreak in the field.ImportanceRalstonia solanacearum, a globally distributed wilt pathogen of many high-value crops, is spread via diseased plant material and contaminated soil, tools, and irrigation water. The Race 3 biovar 2 Select Agent subgroup of R. solanacearum is subject to stringent and constantly evolving regulations intended to prevent pathogen introduction or release. We validated eradication and inactivation methods that can be used by: 1) growers seeking to disinfest water and manage bacterial wilt disease outbreaks; 2) researchers who must remain in compliance with regulations; and 3) regulators who are expected to define containment practices. Relevant to all these stakeholders, we show that while cultured R. solanacearum cells are sensitive to relatively low levels of oxidative chemicals, dessication, and heat, more aggressive treatment such as autoclaving or incineration is required to eradicate R. solanacearum cells growing inside plant material.
Evolution of transposable element-derived enhancer activity
Authors: Du Alan Y. , Zhuo Xiaoyu , Sundaram Vasavi , Jensen Nicholas O. , Chaudhari Hemangi G. , Saccone Nancy L. , Cohen Barak A. , Wang Ting 
Published: March 2022

AbstractMany transposable elements (TEs) contain transcription factor binding sites and are implicated as potential regulatory elements. However, TEs are rarely functionally tested for regulatory activity, which in turn limits our understanding of how TE regulatory activity has evolved. We systematically tested the human LTR18A subfamily for regulatory activity using massively parallel reporter assay (MPRA) and found AP-1 and C/EBP-related binding motifs as drivers of enhancer activity. Functional analysis of evolutionarily reconstructed ancestral sequences revealed that LTR18A elements have generally lost regulatory activity over time through sequence changes, with the largest effects occurring due to mutations in the AP-1 and C/EBP motifs. We observed that the two motifs are conserved at higher rates than expected based on neutral evolution. Finally, we identified LTR18A elements as potential enhancers in the human genome, primarily in epithelial cells. Together, our results provide a model for the origin, evolution, and co-option of TE-derived regulatory elements.
The effect of waning on antibody levels and memory B cell recall following SARS-CoV-2 infection or vaccination
Authors: Forgacs David , Moraes Vanessa S. , Hanley Hannah B. , Gattiker Jasper L. , Jefferson Alexandria M. , Ross Ted M. 
Published: March 2022

AbstractAs of March 2022, there have been over 450 million reported SARS-CoV-2 cases worldwide, and more than 4 billion people have received their primary series of a COVID-19 vaccine. In order to longitudinally track SARS-CoV-2 antibody levels in people after vaccination or infection, a large-scale COVID-19 sero-surveillance progam entitled SPARTA (SeroPrevalence and Respiratory Tract Assessment) was established early in the pandemic. Anti-RBD antibody levels were tracked in more than 1,000 people. There was no significant decrease in antibody levels during the first 14 months after infection in unvaccinated participants, however, significant waning of antibody levels was observed following vaccination, regardless of previous infection status. Moreover, participants who were pre-immune to SARS-CoV-2 prior to vaccination seroconverted to significantly higher antibody levels, and antibodies were maintained at significantly higher levels than in previously infected, unvaccinated participants. This pattern was entirely due to differences in the magnitude of the initial seroconversion event, and the rate of antibody waning was not significantly different based on the pre-immune status. Participants who received a third (booster) dose of an mRNA vaccine not only increased their anti-RBD antibody levels ∼14-fold, but they also had ∼3 times more anti-RBD antibodies compared to the peak of their antibody levels after receiving their primary vaccine series. In order to ascertain whether the presence of serum antibodies is important for long-term seroprotection, PBMCs from 13 participants who lost all detectable circulating antibodies after vaccination or infection were differentiated into memory cells in vitro. There was a significant recall of memory B cells in the absence of serum antibodies in 70% of the vaccinated participants, but not in any of the infected participants. Therefore, there is a strong connection between anti-RBD antibody levels and the effectiveness of memory B cell recall.
A coevolution experiment reveals parallel mutations in the AcrA-AcrB-TolC efflux pump that contributes to bacterial antibiotic resistance
Authors: Chodkowski John L. , Shade Ashley 
Published: March 2022

AbstractOne interference mechanism of bacterial competition is the production of antibiotics. Bacteria exposed to antibiotics can resist antibiotic inhibition through intrinsic and/or acquired mechanisms. Here, we performed a coevolution experiment to understand long-term consequences of antibiotic production and antibiotic resistance for two environmental bacterial strains. We grew five independent lines of the antibiotic-producing environmental strain, Burkholderia thailandensis E264, and the antibiotic-inhibited environmental strain, Flavobacterium johnsoniae UW101, together and separately on agar plates for 7.5 months (1.5 month incubations), transferring each line five times to new agar plates. We first observed that the F. johnsoniae ancestor could tolerate the B. thailandensis-produced antibiotic through efflux mechanisms. We then sequenced the genomes of clonal isolates from the coevolved and monoculture F. johnsoniae lines, and uncovered mutational ramifications to the long-term antibiotic exposure. The coevolved genomes from F. johnsoniae revealed four potential mutational signatures of antibiotic resistance that were not observed in the evolved monoculture lines. Two mutations were found in tolC: one corresponding to a 33 bp deletion and the other corresponding to a nonsynonymous mutation. A third mutation was observed as a 1 bp insertion coding for a RagB/SusD nutrient uptake protein. The last mutation was a G83R nonsynonymous mutation in acetyl-coA carboxylayse carboxyltransferase subunit alpha (AccA). Placing the tolC 33 bp deletion back into the F. johnsoniae ancestor conferred some antibiotic resistance, but not to the degree of resistance observed in coevolved lines. Furthermore, the accA mutation matched a previously described mutation conferring resistance to B. thailandensis-produced thailandamide. Analysis of B. thailandensis transposon mutants for thailandamide production revealed that thailandamide was bioactive against F. johnsoniae, but also suggested that additional B. thailandensis-produced antibiotics were involved in the inhibition of F. johnsoniae. This study reveals how long-term interspecies chemical interactions can result in a novel mutation in efflux that contribute to antibiotic resistance.