bluuebunny/crossref_metadata_2025_split huggingface dataset:
Letter to editor: Emerging public health challenge in UK: perception and belief on increased COVID19 death among BAME healthcare workers
Authors: Omotade I , Flisher P , Sivalingam T , Gupta S , Kuah J 
Published: August 2021

Abstract
A cross-sectional survey of Black Asian and minority ethnic (BAME) health care workers evaluating their perception and belief on increased Coronavirus disease-19 (COVID-19) death among BAME health care workers was conducted in Leicester. They found that 72% of respondents had some form of impact on their mental health but the majority were satisfied with the overall support they received from local health care providers. In conclusion, adequate culturally competent mental health support is necessary as the BAME workforce is routinely involved in frontline work.
A Theory of Liquidity Spillover between Bond and CDS Markets
Authors: Sambalaibat Batchimeg 
Published: August 2021

Abstract
I build a search model of bond and credit default swap (CDS) markets with endogenous investor participation and show that shorting bonds through CDS increases the liquidity and price of bonds. By allowing investors to trade the credit risk of bonds without trading the bonds, CDS introduction expands the set of feasible trades and attracts investors into the credit market. Because search is nondirected within the credit market, new investors also trade bonds and consequently increase their price and liquidity. My results suggest that naked CDS bans increased sovereigns’ borrowing costs and thereby exacerbated the 2010–2012 European debt crisis.
The molecular and cellular basis of copper dysregulation and its relationship with human pathologies
Authors: Maung May T. , Carlson Alyssa , Olea‐Flores Monserrat , Elkhadragy Lobna , Schachtschneider Kyle M. , Navarro‐Tito Napoleon , Padilla‐Benavides Teresita 
Published: August 2021

AbstractCopper (Cu) is an essential micronutrient required for the activity of redox‐active enzymes involved in critical metabolic reactions, signaling pathways, and biological functions. Transporters and chaperones control Cu ion levels and bioavailability to ensure proper subcellular and systemic Cu distribution. Intensive research has focused on understanding how mammalian cells maintain Cu homeostasis, and how molecular signals coordinate Cu acquisition and storage within organs. In humans, mutations of genes that regulate Cu homeostasis or facilitate interactions with Cu ions lead to numerous pathologic conditions. Malfunctions of the Cu+‐transporting ATPases ATP7A and ATP7B cause Menkes disease and Wilson disease, respectively. Additionally, defects in the mitochondrial and cellular distributions and homeostasis of Cu lead to severe neurodegenerative conditions, mitochondrial myopathies, and metabolic diseases. Cu has a dual nature in carcinogenesis as a promotor of tumor growth and an inducer of redox stress in cancer cells. Cu also plays role in cancer treatment as a component of drugs and a regulator of drug sensitivity and uptake. In this review, we provide an overview of the current knowledge of Cu metabolism and transport and its relation to various human pathologies.
The impact of seasonal factors on the COVID-19 pandemic waves
Authors: Nesteruk Igor , Rodionov Oleksii , Nikitin Anatolii 
Published: August 2021

ABSTRACTThe daily number of new COVID-19 cases per capita is an important characteristic of the pandemic dynamics indicating the appearance of new waves (e.g., caused by new coronavirus strains) and indicate the effectiveness of quarantine, testing and vaccination. Since this characteristic is very random and demonstrates some weekly period, we will use the 7-days smoothing. The second year of the pandemic allows us to compare its dynamics in the spring and the summer of 2020 with the same period in 2021 and investigate the influence of seasonal factors. We have chosen some northern countries and regions: Ukraine, EU, the UK, USA and some countries located in tropical zone and south semi-sphere: India, Brazil, South Africa and Argentina. The dynamics in these regions was compared with COVID-19 pandemic dynamics in the whole world. Some seasonal similarities are visible only for EU and South Africa. In 2020, the southern countries demonstrated the exponential growth, but northern regions showed some stabilization trends.
Autoimmune Alleles at the Major Histocompatibility Locus Modify Melanoma Susceptibility
Authors: Talwar James , Laub David , Pagadala Meghana , Castro Andrea , Lewis McKenna , Luebeck Georg E. , Gorman Bryan , Pan Cuiping , Dong Frederick N. , Markianos Kyriacos , Hauger Richard , Pyarajan Saiju , Tsao Philip S. , Morris Gerald P. , Salem Rany M. , Thompson Wesley K. , Curtius Kit , Zanetti Maurizio , Carter Hannah 
Published: August 2021

AbstractAutoimmunity and cancer represent two different aspects of immune dysfunction. Autoimmunity is characterized by breakdowns in immune self-tolerance, while impaired immune surveillance can allow for tumorigenesis. The class I major histocompatibility complex (MHC-I), which displays derivatives of the cellular peptidome for immune surveillance by CD8+ T cells, serves as a common genetic link between these conditions. As melanoma-specific CD8+ T-cells have been shown to target melanocyte-specific peptide antigens more often than melanoma-specific antigens, we investigated whether vitiligo and psoriasis predisposing MHC-I alleles conferred a melanoma protective effect. In individuals with cutaneous melanoma from both The Cancer Genome Atlas (N = 451) and an independent validation cohort (N = 586), MHC-I autoimmune allele carrier status was significantly associated with a later age of melanoma diagnosis. Furthermore, MHC-I autoimmune allele carriers were significantly associated with decreased risk of developing melanoma in the Million Veterans Program cohort (OR = 0.962, p = 0.024). Existing melanoma polygenic risk scores (PRS) did not predict autoimmune allele carrier status, suggesting these alleles provide new risk-relevant information. Mechanisms of autoimmune protection were neither associated with improved melanoma-driver mutation association nor improved gene-level conserved antigen presentation relative to common alleles (population frequency > 1%). However, autoimmune alleles showed higher affinity relative to common alleles for particular windows of melanocyte conserved antigens suggesting a potential relationship between antigen processing, binding, and cell-surface presentation. Overall, this study presents evidence that MHC-I autoimmune risk alleles modulate melanoma risk unaccounted for by current PRS.
Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant
Authors: Liu Yang , Liu Jianying , Johnson Bryan A. , Xia Hongjie , Ku Zhiqiang , Schindewolf Craig , Widen Steven G. , An Zhiqiang , Weaver Scott C. , Menachery Vineet D. , Xie Xuping , Shi Pei-Yong 
Published: August 2021

AbstractSARS-CoV-2 Delta variant has rapidly replaced the Alpha variant around the world. The mechanism that drives this global replacement has not been defined. Here we report that Delta spike mutation P681R plays a key role in the Alpha-to-Delta variant replacement. In a replication competition assay, Delta SARS-CoV-2 efficiently outcompeted the Alpha variant in human lung epithelial cells and primary human airway tissues. Delta SARS-CoV-2 bearing the Alpha-spike glycoprotein replicated less efficiently than the wild-type Delta variant, suggesting the importance of Delta spike in enhancing viral replication. The Delta spike has accumulated mutation P681R located at a furin cleavage site that separates the spike 1 (S1) and S2 subunits. Reverting the P681R mutation to wild-type P681 significantly reduced the replication of Delta variant, to a level lower than the Alpha variant. Mechanistically, the Delta P681R mutation enhanced the cleavage of the full-length spike to S1 and S2, leading to increased infection via cell surface entry. In contrast, the Alpha spike also has a mutation at the same amino acid (P681H), but the spike cleavage from purified Alpha virions was reduced compared to the Delta spike. Collectively, our results indicate P681R as a key mutation in enhancing Delta variant replication via increased S1/S2 cleavage. Spike mutations that potentially affect furin cleavage efficiency must be closely monitored for future variant surveillance.
Differential regulation and production of secondary metabolites among isolates of the fungal wheat pathogenZymoseptoria tritici
Authors: Amine Hassani M. , Oppong-Danquah Ernest , Feurtey Alice , Tasdemir Deniz , Stukenbrock Eva H. 
Published: August 2021

SummaryThe genome of the wheat pathogenic fungus,Zymoseptoria tritici,represents extensive presence-absence variation in gene content. Here, we addressed variation in biosynthetic gene clusters (BGCs) content and biochemical profiles among three isolates. We analysed secondary metabolite properties based on genome, transcriptome and metabolome data. The isolates represent highly distinct genome architecture, but harbor similar repertoire of BGCs. Expression profiles for most BGCs show comparable patterns of regulation among the isolates, suggesting a conserved “biochemical infection program”. For all three isolates, we observed a strong up-regulation of an abscisic acid (ABA) gene cluster during biotrophic host colonization, indicating thatZ. triticipotentially interfere with host defenses by the biosynthesis of this phytohormone. Further, duringin vitrogrowth the isolates show similar metabolomes congruent with the predicted BGC content. We assessed if secondary metabolite production is regulated by histone methylation using a mutant impaired in formation of facultative heterochromatin (H3K27me3). In contrast to other ascomycete fungi, chromatin modifications play a less prominent role in regulation of secondary metabolites. In summary, we show thatZ. triticihas a conserved program of secondary metabolite production contrasting the immense variation in effector expression, some of these metabolites might play a key role during host colonization.Originality-Significance StatementZymoseptoria triticiis one of the most devastating pathogens of wheat. So far the molecular determinants of virulence and their regulation are poorly understood. Previous studies have focused on proteinasous virulence factors and their extensive diversity. In this study, we focus on secondary metabolites produced byZ. tritici. Using a comparative framework, we here characterize core and non-core metabolites produced byZ. triticiby combining genome, transcriptome and metabolome datasets. Our findings indicate highly conserved biochemical profiles contrasting genetic and phenotypic diversity of the field isolates investigated here. This discovery has relevance for future crop protection strategies.
microRNA Expression Levels Change in Neonatal Patients During and After Exposure to Cardiopulmonary Bypass
Authors: Hsieh Lance , Tu Lan , Paquette Alison , Kibiryeva Nataliya , Marshall Jennifer , Bittel Douglas , O’Brien James , Vickers Kasey , Pastuszko Peter , Nigam Vishal 
Published: August 2021

ABSTRACTObjectivesThe systemic inflammation that occurs after exposure to cardiopulmonary bypass (CPB), which is especially severe in neonatal patients, is associated with poorer outcomes and is not well understood. In order to gain deeper insight into how exposure to bypass activates inflammatory responses in circulating leukocytes, we studied changes in microRNA (miRNA) expression during and after exposure to bypass. miRNAs are small non-coding RNAs that have important roles in modulating protein levels and function of cells.MethodsWe performed miRNA-Sequencing on leukocytes isolated from neonatal cardiopulmonary bypass patients (N=5) at 7 timepoints during the process of CPB, including prior to the initiation of bypass, during bypass, and at three time points during the first 24 hours after weaning from bypass. We identified significant differentially expressed miRNAs using generalized linear regression models, and miRNAs were defined as statistically significant using an FDR adjusted p <0.05. We identified gene targets of these miRNAs using the Targetscan database, and identified significantly enriched biological pathways for these gene targets.ResultsWe identified 54 miRNAs with differential expression during and after CPB. These miRNAs clustered into 3 groups, including miRNAs that were increased during and after CPB (3 miRNAs), miRNAs that decreased during and after CPB (10 miRNAs), and miRNAs that decreased during CPB but then increased 8-24 hours after CPB. 38.9% of the target genes of these miRNAs were significantly differentially expressed in our previous study. miRNAs with altered expression levels are predicted to significantly modulate pathways related to inflammation and signal transduction.ConclusionsThe unbiased profiling of the miRNA changes that occur in the circulating leukocytes of bypass patients provides deeper insight into the mechanisms that underpin the systemic inflammatory response that occurs in patients after exposure to cardiopulmonary bypass. These data will help the development of novel treatments and biomarkers for bypass associated inflammation.
Cross-species incompatibility between a DNA satellite and the Drosophila Spartan homolog poisons germline genome integrity
Authors: Brand Cara L. , Levine Mia T. 
Published: August 2021

ABSTRACTSatellite DNA spans megabases of eukaryotic sequence and evolves rapidly. Paradoxically, satellite-rich genomic regions mediate strictly conserved, essential processes like chromosome segregation and nuclear structure. A leading resolution to this paradox posits that satellite DNA and satellite-associated chromosomal proteins coevolve to preserve these essential functions. We experimentally test this model of intra-genomic coevolution by conducting the first evolution-guided manipulation of both chromosomal protein and DNA satellite. The 359bp satellite spans an 11Mb array in D. melanogaster that is absent from its sister species, D. simulans. This species-specific DNA satellite colocalizes with the adaptively evolving, ovary-enriched protein, Maternal Haploid (MH)–the Drosophila homolog of Spartan. To determine if MH and 359 coevolve, we swapped the D. simulans version of MH (“MH[sim]”) into D. melanogaster. MH[sim] triggers ovarian cell death, reduced ovary size, and loss of mature eggs. Surprisingly, the D. melanogaster mh null mutant has no such ovary phenotypes, suggesting that MH[sim] is toxic in a D. melanogaster background. Using both cell biology and genetics, we discovered that MH[sim] poisons oogenesis through a DNA damage pathway. Remarkably, deleting the D. melanogaster-specific 359 satellite array completely restores mh[sim] germline genome integrity and fertility, consistent with a history of coevolution between these two fast-evolving loci. Germline genome integrity and fertility are also restored by overexpressing Topoisomerase II (Top2), suggesting that MH[sim] interferes with Top2-mediated processing of 359. The observed 359-MH[sim] cross-species incompatibility supports a model under which ostensibly inert repetitive DNA and essential chromosomal proteins must coevolve to preserve germline genome integrity.
Gametogenesis in the green seaweed Ulva mutabilis coincides with massive transcriptional restructuring
Authors: Liu Xiaojie , Blomme Jonas , Bogaert Kenny , D’hondt Sofie , Wichard Thomas , De Clerck Olivier 
Published: August 2021

AbstractThe molecular mechanism underlying sexual reproduction in land plants is well understood in model plants and is a target for crop improvement. However, unlike land plants, the genetic basis involved in triggering reproduction and gamete formation remains elusive in most seaweeds, which are increasingly viewed as an alternative source of functional food and feedstock for energy applications. Here, gametogenesis of Ulva mutabilis, a model organism for green seaweeds, is studied. We analyze transcriptome dynamics at different time points during gametogenesis following induction of reproduction by fragmentation and removal of sporulation inhibitors. Analyses demonstrate that 45% of the genes in the genome are differentially expressed during gametogenesis. We identified several transcription factors that potentially play a key role in the early gametogenesis of Ulva given the function of their homologs in higher plants and microalgae. In particular, the detailed expression pattern of an evolutionary conserved transcription factor containing an RWP-RK domain suggests a key role during Ulva gametogenesis. The identification of putative master regulators of gametogenesis provides a starting point for further functional characterization.HighlightTranscriptomic analyses of gametogenesis in the green seaweed Ulva highlight the importance of a conserved RWP-RK transcription factor in induction of sexual reproduction.
Caught in Motion: Human NTHL1 Undergoes Interdomain Rearrangement Necessary for Catalysis
Authors: Carroll Brittany L. , Zahn Karl E. , Hanley John P. , Wallace Susan S. , Dragon Julie A. , Doublié Sylvie 
Published: August 2021

ABSTRACTBase excision repair (BER) is the main pathway protecting cells from the continuous damage to DNA inflicted by reactive oxygen species. BER is initiated by DNA glycosylases, each of which repairs a particular class of base damage. NTHL1, a bifunctional DNA glycosylase, possesses both glycolytic and ß-lytic activities with a preference for oxidized pyrimidine substrates. Defects in human NTLH1 drive a class of polyposis colorectal cancer. We report the first X-ray crystal structure of hNTHL1, revealing an open conformation not previously observed in the bacterial orthologs. In this conformation, the six-helical barrel domain comprising the helix-hairpin-helix (HhH) DNA binding motif is tipped away from the iron sulphur cluster-containing domain, requiring a conformational change to assemble a catalytic site upon DNA binding. We found that the flexibility of hNTHL1 and its ability to adopt an open configuration can be attributed to an interdomain linker. Swapping the human linker sequence for that of Escherichia coli yielded a protein chimera that crystallized in a closed conformation and had a lower binding affinity for lesion-containing DNA. This large scale interdomain rearrangement during catalysis is unprecedented for a HhH superfamily DNA glycosylase and provides important insight into the molecular mechanism of hNTHL1.
Nearest-neighbor effects modulate loxP spacer DNA chemical shifts and guide oligonucleotide design for NMR studies
Authors: Wagner Nicole , Foster Mark P. 
Published: August 2021

AbstractCre recombinase catalyzes site-specific DNA recombination at pseudo-palindromic loxP sites through two rounds of strand cleavage, exchange, and religation. Cre is a potential gene editing tool of interest due its lack of requirements for external energy sources or host factors, as well as the fact that it does not generate potentially cytotoxic double-stranded DNA breaks. However, broader applications of Cre in editing noncanonical target sequences requires a deeper understanding of the DNA features that enable target site selection and efficient recombination. Although Cre recombines loxP DNA in a specific and ordered fashion, it makes few direct contacts to the loxP spacer, the region where recombination occurs. Furthermore, little is known about the structural and dynamic features of the loxP spacer that make it a suitable target for Cre. To enable NMR spectroscopic studies of the spacer, we have aimed to identify a fragment of the 34-bp loxP site that retains the structural features of the spacer while minimizing the spectral crowding and line-broadening seen in longer oligonucleotides. We report sequential backbone resonance assignments for loxP oligonucleotides of varying lengths and evaluate chemical shift differences, Δδ, between the oligos. Analysis of flanking sequence effects and mutations on spacer chemical shifts indicates that nearest-neighbor and next-nearest-neighbor effects dominate the chemical environment experienced by the spacer. We have identified a 16-bp oligonucleotide that adequately preserves the structural environment of the spacer, setting the stage for NMR-based structure determination and dynamics investigations.
DDX41 is needed for pre-and post-natal hematopoietic stem cell differentiation in mice
Authors: Ma Jing , Mahmud Nadim , Bosland Maarten C. , Ross Susan R. 
Published: August 2021

AbstractDDX41 is a tumor suppressor frequently mutated in human myeloid neoplasms. DDX41 binds to DNA/RNA hybrids and interacts with spliceosome component (1, 2). How it affects hematopoiesis is still unclear. Using a knockout mouse model, we demonstrate that DDX41 is required for mouse hematopoietic stem and progenitor cell (HSPC) survival and differentiation. Lack of DDX41 particularly affected myeloid progenitor development, starting at embryonic day 13.5. DDX41-deficient fetal liver and adult bone marrow (BM) cells were unable to rescue mice from lethal irradiation after transplantation. DDX41 knockout stem cells were also defective in ex vivo colony forming assays. RNASeq analysis of lineage-negative, cKit+Sca1+ cells isolated from fetal liver demonstrated that the expression of many genes associated with hematopoietic differentiation were altered in DDX41 knockout cells. Furthermore, altered splicing of genes involved in key biological processes were observed. Our data reveal a critical role for DDX41 in HSPC differentiation and myeloid progenitor development, likely through its regulation of gene expression programs and splicing.SignificanceDDX41 is a tumor suppressor in hematologic malignancies. However, whether DDX41 functions in hematopoiesis and myeloid cell differentiation is not known. Here we show that in mice, loss of DDX41 in hematopoietic stem cells (HSCs) leads to defects in hematopoietic development. The myeloid lineage was particularly affected as early as pre-natal stages. Transcriptional profiling of embryonic HSCs revealed that there were global changes in gene expression and splicing due to lack of DDX41. Collectively, the study uncovers a new function of DDX41 in HSC differentiation and could provide molecular targets for treatment of myeloid differentiation disorders.