bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic epidemiology of SARS-CoV-2 divulge B.1, B.1.36, and B.1.1.7 as the most dominant lineages in first, second, and third wave of SARS-CoV-2 infections in Pakistan
Authors: Basheer Atia , Zahoor Imran 
Published: July 2021

AbstractThe present study aims to investigate the genomic variability and epidemiology of SARS-CoV-2 in Pakistan along with their role in the spread and severity of infection during the three waves of COVID-19. A total of 453 genomic sequences of Pakistani SARS-CoV-2 were retrieved from GISAID and subjected to MAFFT-based alignment and QC check which resulted in removal of 53 samples. The remaining 400 samples were subjected to Pangolin-based genomic lineage identification. And to infer our SARS-CoV-2 time-scaled and divergence phylogenetic trees, 3,804 selected global reference sequences plus 400 Pakistani samples were used for the Nextstrain analysis with Wuhan/Hu-1/2019, as reference genome. Finally, maximum likelihood based phylogenetic tree was built by using the Nextstrain & coverage map was created by employing Nextclade. And by using the amino acid subsitutions the maximum likelihood phylogenetic trees were developed for each wave, separately. Our results reveal the circulation of 29 lineages, belonging to following 7 clades G, GH, GR, GRY, L, O, & S in the three waves. From first wave, 16 genomic lineages of SARS-CoV-2 were identified with B.1(24.7%), B.1.36(18.8%), & B.1.471(18.8%) as the most prevalent lineages respectively. The second wave data showed 18 lineages, 10 of which were overlapping with the first wave suggesting that those variants could not be contained during the first wave. In this wave, a new lineage, AE.4, was reported from Pakistan for the very first time in the world. However, B.1.36 (17.8%), B.1.36.31 (11.9%), B.1.1.7 (8.5%) & B.1.1.1 (5.9%) were the major lineages in second wave. Third wave data showed the presence of 9 lineages with Alpha/B.1.1.7 (72.7%), Beta/B.1.351 (12.99%), & Delta/B.1.617.2 (10.39%) as the most predominant variants. It is suggested that these VOCs should be contained at the earliest in order to prevent any devastating outbreak of SARS-CoV-2 in the country.
Human brain anatomy reflects separable genetic and environmental components of socioeconomic status
Authors: Kweon Hyeokmoon , Aydogan Gökhan , Dagher Alain , Bzdok Danilo , Ruff Christian C. , Nave Gideon , Farah Martha J. , Koellinger Philipp D. 
Published: July 2021

AbstractRecent studies report that socioeconomic status (SES) correlates with brain structure. Yet, such findings are variable and little is known about underlying causes. We present a well-powered voxel-based analysis of grey matter volume (GMV) across levels of SES, finding many small SES effects widely distributed across the brain, including cortical, subcortical and cerebellar regions. We also construct a polygenic index of SES to control for the additive effects of common genetic variation related to SES, which attenuates observed SES-GMV relations, to different degrees in different areas. Remaining variance, which may be attributable to environmental factors, is substantially accounted for by body mass index, a marker for lifestyle related to SES. In sum, SES affects multiple brain regions through measurable genetic and environmental effects.One-sentence SummarySocioeconomic status is linked with brain anatomy through a varying balance of genetic and environmental influences.
Population genomic consequences of novel life history and mating system adaptation to a geothermal soil mosaic in yellow monkeyflowers (Mimulus guttatus)
Authors: Kolis Kory M. , Berg Colette S. , Nelson Thomas C. , Fishman Lila 
Published: July 2021

AbstractLocal selection can promote phenotypic divergence despite gene flow across habitat mosaics, but adaptation itself may generate substantial barriers to genetic exchange. In plants, life-history, phenology, and mating system divergence have been particularly proposed to promote genetic differentiation in sympatry. In this study, we investigate phenotypic and genetic variation in Mimulus guttatus (yellow monkeyflowers) across a geothermal soil mosaic in Yellowstone National Park (YNP). Plants from thermal annual and nonthermal perennial habitats were heritably differentiated for life history and mating system traits, consistent with local adaptation to the ephemeral thermal-soil growing season. However, genome-wide genetic variation primarily clustered plants by geographic region, with little variation sorting by habitat. The one exception was an extreme thermal population also isolated by a 200m geographical gap. Individual inbreeding coefficients (FIS) were higher (and predicted by trait variation) in annual plants and annual pairs showed greater isolation by distance at local (<1km) scales. Finally, YNP adaptation does not re-use a widespread inversion polymorphism diagnostic of annual vs. perennial M. guttatus range-wide, suggesting a novel genetic mechanism. Overall, this work suggests that life history and mating system adaptation strong enough to shape individual mating patterns does not necessarily generate incipient speciation without geographical barriers.
Viruses of Asgard archaea
Authors: Medvedeva Sofia , Sun Jiarui , Yutin Natalya , Koonin Eugene V. , Nunoura Takuro , Rinke Christian , Krupovic Mart 
Published: July 2021

AbstractAsgardarchaeota encode many eukaryotic signature proteins and are widely considered to represent the closest archaeal relatives of eukaryotes. Whether similarities between Asgard archaea and eukaryotes extend to their viromes remains unknown. Here we present 20 metagenome-assembled genomes of Asgardarchaeota from deep-sea sediments of the basin off the Shimokita Peninsula, Japan. By combining CRISPR spacer search of metagenomic sequences with phylogenomic analysis, we identify three family-level groups of viruses associated with Asgard archaea. The first group, Verdandiviruses, includes tailed viruses of the realmDuplodnaviria, the second one, Skuldviruses, consists of viruses with predicted icosahedral capsids that belong to the realmVaridnaviria, and the third group, Wyrdviruses, is related to spindle-shaped viruses previously identified in other archaea. More than 90% of the proteins encoded by these putative viruses of Asgard archaea show no sequence similarity to proteins encoded by other known viruses. Nevertheless, all three proposed families consist of viruses typical of prokaryotes, providing no indication of a specific evolutionary relationship between viruses infecting Asgard archaea and eukaryotes. Verdandiviruses and skuldviruses are likely to be lytic, whereas wyrdviruses, similar to all other known spindle-shaped viruses, probably establish chronic infection and are released without host cell lysis. All three groups of viruses were identified in sediment samples from distinct geographical locations and are expected to play important roles in controlling the Asgard archaea populations in deep-sea ecosystems.
The META tool optimizes metagenomic analyses across sequencing platforms and classifiers
Authors: Player Robert A. , Aguinaldo Angeline M. , Merritt Brian B. , Maszkiewicz Lisa N. , Adeyemo Oluwaferanmi E. , Forsyth Ellen R. , Verratti Kathleen J. , Chee Brant W. , Grady Sarah L. , Bradburne Christopher E. 
Published: July 2021

ABSTRACTA major challenge in the field of metagenomics is the selection of the correct combination of sequencing platform and downstream metagenomic analysis algorithm, or ‘classifier’. Here, we present the Metagenomic Evaluation Tool Analyzer (META), which produces simulated data and facilitates platform and algorithm selection for any given metagenomic use case. META-generated in silico read data are modular, scalable, and reflect user-defined community profiles, while the downstream analysis is done using a variety of metagenomic classifiers. Reported results include information on resource utilization, time-to-answer, and performance. Real-world data can also be analyzed using selected classifiers and results benchmarked against simulations. To test the utility of the META software, simulated data was compared to real-world viral and bacterial metagenomic samples run on four different sequencers and analyzed using 12 metagenomic classifiers. Lastly, we introduce ‘META Score’: a unified, quantitative value which rates an analytic classifier’s ability to both identify and count taxa in a representative sample.
Placental gene expression-based cell type deconvolution: Cell proportions drive preeclampsia gene expression differences
Authors: Campbell Kyle A , Colacino Justin A , Puttabyatappa Muraly , Dou John F , Elkin Elana R , Hammoud Saher S , Domino Steven E , Dolinoy Dana C , Goodrich Jaclyn M , Loch-Caruso Rita , Padmanabhan Vasantha , Bakulski Kelly M 
Published: July 2021

AbstractThe placenta mediates adverse pregnancy outcomes, including preeclampsia, which is characterized by gestational hypertension and proteinuria. Placental cell type heterogeneity in preeclampsia is not well-understood and limits mechanistic interpretation of bulk gene expression measures. We generated single-cell RNA-sequencing samples for integration with existing data to create the largest deconvolution reference of 19 fetal and 8 maternal cell types from placental villous tissue at term (n=15,532 cells). We deconvoluted eight published microarray case-control studies of preeclampsia (n=330). Deconvolution revealed excess extravillous trophoblasts and fewer mesenchymal cells. Adjustment for cellular composition reduced preeclampsia-associated differentially expressed genes (FDR<0.05) from 1,224 to 0, whereas pathway alterations exhibiting a metabolic adaptation to hypoxia were robust to cell type adjustment. Cellular composition explained 35.1% of the association between preeclampsia andFLT1overexpression. Our findings indicate substantial placental cellular heterogeneity in preeclampsia that predicts previously observed bulk gene expression differences. Our deconvolution reference lays the groundwork for cellular heterogeneity-aware investigation into placental dysfunction and adverse birth outcomes.
NEAT-seq: Simultaneous profiling of intra-nuclear proteins, chromatin accessibility, and gene expression in single cells
Authors: Chen Amy F , Parks Benjamin , Kathiria Arwa S , Ober-Reynolds Benjamin , Goronzy Jorg , Greenleaf William J 
Published: July 2021

AbstractOligonucleotide-conjugated antibodies1 have allowed for joint measurement of surface protein abundance and the transcriptome in single cells using high-throughput sequencing. Extending these measurements to gene regulatory proteins in the nucleus would provide a powerful means to link changes in abundance of trans-acting TFs to changes in activity of cis-acting elements and expression of target genes. Here, we introduce Nuclear protein Epitope, chromatin Accessibility, and Transcriptome sequencing (NEAT-seq), a technique to simultaneously measure nuclear protein abundance, chromatin accessibility, and the transcriptome in single cells. We apply this technique to profile CD4 memory T cells using a panel of master transcription factors (TFs) that drive distinct helper T cell subsets and regulatory T cells (Tregs) and identify examples of TFs with regulatory activity gated by three distinct mechanisms: transcription, translation, and regulation of chromatin binding. Furthermore, we identify regulatory elements and target genes associated with each TF, which we use to link a non-coding GWAS SNP within a GATA motif to both strong allele-specific chromatin accessibility in cells expressing high levels of GATA3 protein, and a putative target gene.
Optimizing large organ scale micro computed tomography imaging in pig and human hearts using a novel air-drying technique
Authors: Pallares-Lupon N. , Ramlugun G. , Ozenne V. , Duchâteau J. , Delgove A. , Bayer J. , Moreno A. , Constantin M. , Gerneke D. , Sands G.B. , Trew M.L. , Hocini M. , Haissaguerre M. , Vigmond E.J. , Quesson B. , Bernus O. , Walton R.D. 
Published: July 2021

AbstractUnderlying electrical propagation in the heart and potentially fatal arrhythmia is the cardiac microstructure. Despite the critical role of muscle architecture, a non-destructive approach to examine not only myocyte orientation, but cellular arrangement in to laminar organization is lacking in hearts from translational animal models and humans. X-ray micro computed tomography using contrast enhancing agents achieves three-dimensional images at near-histological resolutions. However, imaging large mammalian hearts presents challenges including X-ray over-attenuation and loss of image contrast. The goal of this study was to rethink tissue pre-treatment to optimize, and benefit from micro computed tomography imaging resolution in large tissues. Whole pig and human hearts were dehydrated and perfused with a tissue reinforcing agent, hexamethyldisilazane, and slowly air-dried. Heart morphology was conserved and temporally stable. This enabled direct air-mounting for micro computed tomography imaging. Moreover, the desiccated tissue density was significantly reduced compared to the initial hydrated state (P=0.04). Three-dimensional image reconstructions of air-dried hearts segmented using a single intensity threshold revealed detailed microstructural architecture of myolaminae. Conversely, one-step segmentation of hearts loaded with contrast agents poorly estimated the gross anatomical morphology of the heart and lacked identification of tissue microarchitecture. Air-drying large mammalian hearts optimizes X-ray imaging of cardiac microstructure.
Species-wide phylogenomics of the Staphylococcus aureus agr operon reveals convergent evolution of frameshift mutations
Authors: Raghuram Vishnu , Alexander Ashley M. , Loo Hui Qi , Petit Robert A. , Goldberg Joanna B. , Read Timothy D. 
Published: July 2021

AbstractStaphylococcus aureus is a prominent nosocomial pathogen that causes several life-threatening diseases such as pneumonia and bacteremia. S. aureus modulates expression of its arsenal of virulence factors through sensing and integrating responses to environmental signals. The agr (accessory gene regulator) quorum sensing (QS) system is a major regulator of virulence phenotypes in S. aureus. There are four agr specificity groups each with a different autoinducer peptide sequence (encoded by the agrD gene). Though agr is critical for expression of many toxins, paradoxically, S. aureus strains often have non-functional agr activity due to loss-of-function mutations in the four-gene agr operon. To understand patterns in agr variability across S. aureus, we undertook a species-wide genomic investigation. We developed a software tool (AgrVATE; https://github.com/VishnuRaghuram94/AgrVATE) for typing and detecting frameshift mutations in the agr operon. In an analysis of over 40,000 S. aureus genomes, we showed close association between agr type and S. aureus clonal complex. We also found strong linkage between agrBDC alleles (encoding the peptidase, the autoinducing peptide itself, and the peptide sensor respectively) but not agrA (encoding the -response regulator). More than five percent of genomes were found to have frameshift mutations in the agr operon. Though most mutations occur only once in the entire species, we observed a small number of recurring mutations evolving convergently across different clonal lineages. Phylogenetic patterns suggested that strains with agr frameshifts were evolutionary dead ends. Overall, genomic analysis of agr operon suggests evolution through multiple processes with functional consequences that are not fully understood.ImportanceStaphylococcus aureus is a globally pervasive pathogen that produces a plethora of toxic molecules that can degrade, evade, or inhibit the host immune cells. Production of these toxins is mainly controlled by an active agr quorum sensing system, which senses and responds to bacterial cell density. However, there are many reports of S. aureus strains with genetic changes leading to impaired agr activity, often found during chronic bloodstream infections, and may be associated with increased disease severity. We developed an open-source software called AgrVATE to type agr systems and identify putative frameshifts. We used AgrVATE for a species-wide genomic survey of S. aureus, finding that more than 5 % of strains in the public database had non-functional agr systems. We also provide new insights into the evolution of these genetic mutations in the agr system. Overall, this study contributes to our understanding of a common but relatively understudied means of virulence regulation in S. aureus.
Widespread nociceptive maps in the human neonatal somatosensory cortex
Authors: Jones Laura , Verriotis Madeleine , Cooper Robert J. , Laudiano-Dray Maria Pureza , Rupawala Mohammed , Meek Judith , Fabrizi Lorenzo , Fitzgerald Maria 
Published: July 2021

AbstractTopographic cortical maps are essential for spatial localisation of sensory stimulation and generation of appropriate task-related motor responses. Somatosensation and nociception are finely mapped and aligned in the adult somatosensory (S1) cortex, but in infancy, when pain behaviour is disorganised and poorly directed, nociceptive maps may be less refined. We compared the topographic pattern of S1 activation following noxious (clinically required heel lance) and innocuous (touch) mechanical stimulation of the same skin region in newborn infants (n=32) using multi-optode functional near-infrared spectroscopy (fNIRS). Signal to noise ratio and overall activation area did not differ with stimulus modality. Within S1 cortex, touch and lance of the heel elicit localised, partially overlapping increases in oxygenated haemoglobin (HbO), but while touch activation was restricted to the heel area, lance activation extended into cortical hand regions. The data reveals a widespread cortical nociceptive map in infant S1, consistent with their poorly directed pain behaviour.
Regulation of Mus81-Eme1 structure-specific endonuclease by Eme1 SUMO-binding and Rad3ATR kinase is essential in the absence of Rqh1BLM helicase
Authors: Giaccherini C. , Scaglione S. , Coulon S. , Dehé P.M. , Gaillard P.H.L. 
Published: July 2021

AbstractThe Mus81-Eme1 structure-specific endonuclease is crucial for the processing of DNA recombination and late replication intermediates. In fission yeast, stimulation of Mus81-Eme1 in response to DNA damage at the G2/M transition relies on Cdc2CDK1 and DNA damage checkpoint-dependent phosphorylation of Eme1 and is critical for chromosome stability in absence of the Rqh1BLM helicase. Here we identify Rad3ATR checkpoint kinase consensus phosphorylation sites and two SUMO interacting motifs (SIM) within a short N-terminal domain of Eme1 that is required for cell survival in absence of Rqh1BLM. We show that catalytic stimulation of Mus81-Eme1 depends entirely on direct phosphorylation of Eme1 by Rad3ATR and that while Eme1 also undergoes Chk1-mediated phosphorylation, this is not essential for catalytic modulation. Both Rad3ATR- and Chk1-mediated phosphorylation of Eme1 as well as the SIMs are independently critical for cell fitness in absence of Rqh1BLM and abrogating bimodal phosphorylation of Eme1 along with mutating the SIMs is incompatible with rqh1Δ cell viability. Our findings unravel an elaborate regulatory network that relies on the poorly structured N-terminal domain of Eme1 and which is essential for the vital functions Mus81-Eme1 fulfills in absence of Rqh1BLM.
Patterns of morphological diversification in the Ramphastoidea reveal the dramatic divergence of toucans from a conserved morphotype
Authors: Tamma Krishnapriya , Krishnan Anand , Reddy Sushma 
Published: July 2021

AbstractBackgroundMorphological traits offer insights into an organism’s ecological niche, species interactions, and patterns of community organisation. Pantropical lineages - animals and plants distributed across the three tropical continental regions of Asia, Africa, and America - provide a way to test how different environments and communities influence morphological diversification. Here, we examined a monophyletic group of frugivorous birds, the barbets and toucans (Ramphastoidea), which diversified independently on three continents, to investigate whether clades in each region exhibit similar (phylogenetically constrained) or distinct (ecologically influenced) patterns of morphological diversification.ResultsOur results show that despite differences in community dynamics in these regions, lineage accumulation patterns through time on all three continents are broadly similar, putatively due to phylogenetic niche conservatism. We quantified morphological variation in light of phylogenetic relatedness to further reveal that all barbet lineages across continents occupy a conserved region of morphospace after correcting for variation in size. However, in the Neotropics, one lineage, the toucans, have diverged dramatically from typical barbet space and converged toward (yet are distinct from) the trait space occupied by the distantly related hornbills in Asia and Africa. Additionally, we found no link between climatic variables and morphological traits. We conclude that barbets exhibit a conserved morphotype across continents and have diversified by scaling mainly in body size. However, the absence of other large frugivorous birds may have allowed toucans to diversify into a different region of morphospace of increased bill/wing to tail/wing ratios.ConclusionsA combination of photographic and specimen measurements enabled us to demonstrate the presence of a globally conserved barbet morphotype across three tropical continents. By examining different continental lineages of a single monophyletic bird group, we shed light on the contrasting effects of regional ecological factors and phylogenetic constraints on morphological diversification.
Endogenous protein tagging in medaka using a simplified CRISPR/Cas9 knock-in approach
Authors: Seleit Ali , Aulehla Alexander , Paix Alexandre 
Published: July 2021

AbstractThe CRISPR/Cas9 system has been used to generate fluorescently labelled fusion proteins by homology directed repair in a variety of species. Despite its revolutionary success, there remains an urgent need for increased simplicity and efficiency of genome editing in research organisms. Here, we establish a simplified, highly efficient and precise strategy for CRISPR/Cas9 mediated endogenous protein tagging in medaka (Oryzias latipes). We use a cloning-free approach that relies on PCR amplified donor fragments containing the fluorescent reporter sequences flanked by short homology arms (30-40bp), a synthetic sgRNA and streptavidin tagged Cas9. We generate six novel knock-in lines with high efficiency of F0 targeting and germline transmission. Whole Genome Sequencing (WGS) results reveal single-copy integration events only at the targetedloci. We provide an initial characterization of these fusion-protein lines, significantly expanding the repertoire of genetic tools available in medaka. In particular, we show that themScarlet-pcnaknock-in line has the potential to serve as an organismal-wide label for proliferative zones and an endogenous cell cycle reporter.