bluuebunny/crossref_metadata_2025_split huggingface dataset:
Six new reference-quality bat genomes illuminate the molecular basis and evolution of bat adaptations
Authors: Jebb David , Huang Zixia , Pippel Martin , Hughes Graham M. , Lavrichenko Ksenia , Devanna Paolo , Winkler Sylke , Jermiin Lars S. , Skirmuntt Emilia C. , Katzourakis Aris , Burkitt-Gray Lucy , Ray David A. , Sullivan Kevin A. M. , Roscito Juliana G. , Kirilenko Bogdan M. , Dávalos Liliana M. , Corthals Angelique P. , Power Megan L. , Jones Gareth , Ransome Roger D. , Dechmann Dina , Locatelli Andrea G. , Puechmaille Sebastien J. , Fedrigo Olivier , Jarvis Erich D. , Springer Mark S. , Hiller Michael , Vernes Sonja C. , Myers Eugene W. , Teeling Emma C. 
Published: November 2019

AbstractBats account for ~20% of all extant mammal species and are considered exceptional given their extraordinary adaptations, including biosonar, true flight, extreme longevity, and unparalleled immune systems. To understand these adaptations, we generated reference-quality genomes of six species representing the key divergent lineages. We assembled these genomes with a novel pipeline incorporating state-of-the-art long-read and long-range sequencing and assembly techniques. The genomes were annotated using a maximal evidence approach, de novo predictions, protein/mRNA alignments, Iso-seq long read and RNA-seq short read transcripts, and gene projections from our new TOGA pipeline, retrieving virtually all (>99%) mammalian BUSCO genes. Phylogenetic analyses of 12,931 protein coding-genes and 10,857 conserved non-coding elements identified across 48 mammalian genomes helped to resolve bats’ closest extant relatives within Laurasiatheria, supporting a basal position for bats within Scrotifera. Genome-wide screens along the bat ancestral branch revealed (a) selection on hearing-involved genes (e.g LRP2, SERPINB6, TJP2), which suggest that laryngeal echolocation is a shared ancestral trait of bats; (b) selection (e.g INAVA, CXCL13, NPSR1) and loss of immunity related proteins (e.g. LRRC70, IL36G), including pro-inflammatory NF-kB signalling; and (c) expansion of the APOBEC family, associated with restricting viral infection, transposon activity and interferon signalling. We also identified unique integrated viruses, indicating that bats have a history of tolerating viral pathogens, lethal to other mammal species. Non-coding RNA analyses identified variant and novel microRNAs, revealing regulatory relationships that may contribute to phenotypic diversity in bats. Together, our reference-quality genomes, high-quality annotations, genome-wide screens and in-vitro tests revealed previously unknown genomic adaptations in bats that may explain their extraordinary traits.
Complete genome assembly of theWolbachiaendosymbiont of the horn flyHaematobia irritans irritans:a supergroup A strain with multiple horizontally acquired cytoplasmic incompatibility genes
Authors: Madhav Mukund , Parry Rhys , Morgan Jess A.T. , James Peter , Asgari Sassan 
Published: November 2019

AbstractThe horn fly,Haematobia irritans irritans, is a hematophagous parasite of livestock distributed throughout Europe, Africa, Asia, and the Americas. Welfare losses on livestock due to horn fly infestation are estimated to cost between USD 1-2.5 billion annually in North America and Brazil. The endosymbiotic bacteriumWolbachia pipientisis a maternally inherited manipulator of reproductive biology in arthropods and naturally infects laboratory colonies of horn flies from Kerrville, USA and Alberta, Canada, but has also been identified in wild-caught samples from Canada, USA, Mexico and Hungary. Reassembly of PacBio long-read and Illumina genomic DNA libraries from the KerrvilleH. i. irritansgenome project allowed for a complete and circularised 1.3 MbWolbachiagenome (wHae). Annotation ofwHae yielded 1249 coding genes, 34 tRNAs, three rRNAs, and five prophage regions. Comparative genomics and whole genome Bayesian evolutionary analysis ofwHae compared to publishedWolbachiagenomes suggests thatwHae is most closely related to and diverged fromWolbachiasupergroup A strains known to infectDrosophilaspp. Whole-genome synteny analyses betweenwHae and closely related genomes indicates thatwHae has undergone convoluted genome rearrangements while maintaining high nucleotide identity. Comparative analysis of the cytoplasmic incompatibility (CI) genes ofwHae suggests two phylogenetically distinct CI loci and acquisition of anotherCifBhomolog from phylogenetically distant supergroup AWolbachiastrains suggesting horizontal acquisition of these loci. ThewHae genome provides a resource for future examination of the impactWolbachiamay have in both biocontrol and potential insecticide resistance of horn flies.ImportanceHorn flies,Haematobia irritans, are obligate hematophagous parasites of cattle having significant effects on production and animal welfare. Control of horn flies mainly relies on the use of insecticides, but issues with resistance have increased interest in development of alternative means of control.Wolbachia pipientisis an endosymbiont bacterium known to have a range of effects on host reproduction such as induction of cytoplasmic incompatibility, feminization, male killing, and also impacts on vector transmission. These characteristics ofWolbachiahave been exploited in biological control approaches for a range of insect pests. Here we report the assembly and annotation of the circular genome of theWolbachiastrain of the Kerrickville, USA horn fly (wHae). Annotation ofwHae suggests its unique features including the horizontal acquisition of additional transcriptionally active cytoplasmic incompatibility loci. This study will provide the foundation for futureWolbachia-induced biological effect studies for control of horn flies.
Brain Antibody Sequence Evaluation (BASE): an easy-to-use software for complete data analysis in single cell immunoglobulin cloning
Authors: Reincke S. Momsen , Prüss Harald , Kreye Jakob 
Published: November 2019

AbstractBackgroundRepertoire analysis of patient-derived recombinant monoclonal antibodies is an important tool to study the role of B cells in autoimmune diseases of the human brain and beyond. Current protocols for generation of patient-derived recombinant monoclonal antibody libraries are time-consuming and contain repetitive steps, some of which can be assisted with the help of software automation.ResultsWe developed BASE, an easy-to-use software for complete data analysis in single cell immunoglobulin cloning. BASE consists of two modules: aBASE for immunological annotations and cloning primer lookup, and cBASE for plasmid sequence identity confirmation before expression. Comparing automated BASE analysis with manual analysis we confirmed the validity of BASE output: identity between manual and automated aBASE analysis was 100% for all outputs, except for immunoglobulin isotype determination. In this case, aBASE yielded correct results in 96% of cases, whereas 4% of cases required manual confirmation. cBASE automatically concluded expression recommendations in 89.8% of cases, 91.8% of which were identical to manually derived results and none of them were false-positive.ConclusionsBASE offers an easy-to-use software solution suitable for complete Ig sequence data analysis and tracking during recombinant mcAB cloning from single cells. Plasmid sequence identity confirmation by cBASE offers functionality not provided by existing software solutions in the field and will help to reduce time-consuming steps of the monoclonal antibody generation workflow.
Spotlight on the monitoring of the invasion of a carabid beetle on an oceanic islandover a 100 year period
Authors: Lebouvier M. , Lambret P. , Garnier A. , Frenot Y. , Vernon P. , Renault D. 
Published: November 2019

AbstractThe flightless beetleMerizodus soledadinus, originating from the Falkland Islands, was introduced to the sub-Antarctic Kerguelen Islands. We compiled the existing information on ship visits and landings on these islands to confirm the introduction date ofM. soledadinus. Using data available in the literature, in addition to collecting more than 2000 presence/absence records ofM. soledadinusover the 1991-2018 period, we tracked changes of its abundance and geographical distribution. The range expansion of this nonflying insect was initially slow, but has accelerated over the past two decades in parallel to local increased abundances of the insect’s populations. Human activities may have facilitated colonization of some localities byM. soledadinuswhich is now widely present in the eastern part of the Kerguelen archipelago. This predatory insect represents a major threat for the native invertebrate fauna; in particular, the wingless fliesAnatalanta apteraandCalycopteryx moseleyiwhich are locally displaced and/or eliminated by the beetle. If no control measures, let alone eradication, are practicable, it is essential to limit the transport of this invasive insect along with human activities. Since 2006, the Kerguelen Islands have had the status of a nature reserve, making these results of significant interests for the management of this archipelago, and more generally, emphasizing the importance of long-term biomonitoring programmes for assessing and predicting changes in the distribution of invasive organisms. Strict biosecurity measures have now been established at the Kerguelen Islands, with even greater attention paid to visits to remote sites not yet colonized byM. soledadinus.
Sex-specific genetic effects across biomarkers
Authors: Flynn Emily , Tanigawa Yosuke , Rodriguez Fatima , Altman Russ B. , Sinnott-Armstrong Nasa , Rivas Manuel A. 
Published: November 2019

AbstractSex differences have been shown in laboratory biomarkers; however, the extent to which this is due to genetics is unknown. In this study, we infer sex-specific genetic parameters (heritability and genetic correlation) across 33 quantitative biomarker traits in 181,064 females and 156,135 males from the UK Biobank study. We apply a Bayesian mixture model, Sex Effects Mixture Model, to Genome-wide Association Study summary statistics in order to (1) estimate the contributions of sex to the genetic variance of these biomarkers and (2) identify variants whose statistical association with these traits is sex-specific. We find that the genetics of most biomarker traits are shared between males and females, with the notable exception of testosterone, where we identify 119 female and 444 male-specific variants. These include protein-altering variants in steroid hormone production genes (POR, CYP3A43, UGT2B7). Using the sex-specific variants as genetic instruments for Mendelian Randomization, we find evidence for causal links between testosterone levels and height, body mass index, waist circumference, and type 2 diabetes. We also show that sex-specific polygenic risk score models for testosterone outperform a combined model. Overall, these results demonstrate that while sex has a limited role in the genetics of most biomarker traits, sex plays an important role in testosterone genetics.
Selection of HIV-1 for Resistance to Fifth Generation Protease Inhibitors Reveals Two Independent Pathways to High-Level Resistance
Authors: Spielvogel Ean , Lee Sook-Kyung , Zhou Shuntai , Lockbaum Gordon J. , Henes Mina , Sondegroth Amy , Kosovrasti Klajdi , Nalivaika Ellen A. , Ali Akbar , Yilmaz Nese Kurt , Schiffer Celia A. , Swanstrom Ronald 
Published: November 2019

SummaryDarunavir (DRV) is exceptional among potent HIV-1 protease inhibitors (PIs) in the high drug concentrations that are achived in vivo. Little is known about the de novo resistance pathway for DRV. We have selected for resistance to high drug concentrations against ten PIs and their structural precursor DRV. Mutations accumulated through two pathways (anchored by protease mutations I50V or I84V). Small chemical changes in the inhibitor P1’ side chain led to preferential use of one pathway over the other. Changes in the inhbitor P2’ side chain determined differences in potency that were retained in the resistant viruses. Viral variants from the two pathways showed differential selection of compensatory mutations in Gag cleavage sites. These results reveal the high level of selective pressure that is attainable with fourth generation PIs, and how features of the inhibitor affect both the resistance pathway and the residual potency in the face of resistance.
Characterizing the allele- and haplotype-specific copy number landscape of cancer genomes at single-cell resolution with CHISEL
Authors: Zaccaria Simone , Raphael Benjamin J. 
Published: November 2019

AbstractSingle-cell barcoding technologies have recently been used to perform whole-genome sequencing of thousands of individual cells in parallel. These technologies provide the opportunity to characterize genomic heterogeneity at single-cell resolution, but their extremely low sequencing coverage (<0.05X per cell) has thus far restricted their use to identification of the total copy number of large multi-megabase segments in individual cells. However, total copy numbers do not distinguish between the two homologous chromosomes in humans, and thus provide a limited view of tumor heterogeneity and evolution missing important events such as copy-neutral loss-of-heterozygosity (LOH). We introduce CHISEL, the first method to infer allele- and haplotype-specific copy numbers in single cells and subpopulations of cells by aggregating sparse signal across thousands of individual cells. We applied CHISEL to 10 single-cell sequencing datasets from 2 breast cancer patients, each dataset containing ≈2000 cells. We identified extensive allele-specific copy-number aberrations (CNAs) in these samples including copy-neutral LOH, whole-genome duplications (WGDs), and mirrored-subclonal CNAs in subpopulations of cells. These allele-specific CNAs alter the copy number of genomic regions containing well-known breast cancer genes including TP53, BRCA2, and PTEN but are invisible to total copy number analysis. We utilized CHISEL’s allele- and haplotype-specific copy numbers to derive a more refined reconstruction of tumor evolution: timing allele-specific CNAs before and after WGDs, identifying low-frequency subclones distinguished by unique CNAs, and uncovering evidence of convergent evolution. This reconstruction is supported by orthogonal analysis of somatic single-nucleotide variants (SNVs) obtained by pooling barcoded reads across clones defined by CHISEL.
Physico-biochemical and molecular responses of Acacia auriculiformis to salinity stress
Authors: Gupta Deepak B. , Banerjee Joydeep , Pramanik Krishnendu , Das Arpita , Pal Srikumar 
Published: November 2019

AbstractSalinity limits the growth and yield of many crops across the globe and is considered as major threat to agriculture. Acacia auriculiformis, an important salt tolerant crop, is growing abundantly in the salt-affected mangrove areas of Sunderban, West Bengal, India. In the present study, we have reported the physiological, molecular and antioxidant response of this crop to a gradient of salt treatments ranging between 0 and 800 mM NaCl. As a stress response, the antioxidant enzymes viz. superoxide dismutase (SOD), catalase (CAT) and guaiacol peroxidase (GPX) were highly activated at 200, 400 and 800 mM NaCl respectively. Antioxidant metabolites such as phenols and thiols elevated with increasing salt treatments thus augmenting antioxidant activity with significant positive relationship with phenol content. Similarly, phenylalanine ammonia lyase (PAL) activity was up-regulated in a dose dependent manner with significant relationship with phenol content. This study also reported the phenolic profile for the first time in A. auriculiformis with the abundance of flavonoids. In addition, transcriptional up-regulation of Na+/H+ antiporter gene (NHX1) and the development of robust vascular tissues was noticed at 400 mM NaCl stress compared to control, while further stress at 800 mM NaCl induced poor vascular tissue growth but with higher PAL activity and consequent higher phenol content. Based on this observation, a model for salt tolerance mechanism of A. auriculiformis has been proposed.
The flow of sickle blood through glass capillaries: a point of care application
Authors: Brown Christopher D. , Aprelev Alexey M. , Ferrone Frank A. 
Published: November 2019

AbstractWe show that the characteristic time for sickled blood to traverse 100 µm-diameter glass capillaries can be used as the foundation for a useful point-of-care diagnosis for sickle cell disease. 3.2 cm long capillaries were inserted into a 5 µL drop of blood, and 1/4 µL was spontaneously drawn into the tube. The rate at which the blood traversed the capillary was significantly changed by deoxygenation only for sickle genotypes, a consequence of the increased viscosity of cells containing sickle fibers. Under these conditions, we find deoxygenation causes the time for sickle blood to traverse the capillary to increase to about 3 times its original value, in contrast to normal blood, where the times are equivalent regardless of state of oxygenation. This corresponds to readily-observed time differences of around 10 s for capillary traversal. Such changes are present for blood from homozygous sickle cell patients, as well as heterozygous patients with hemoglobin AS, SC, and Sβ+ thalassemia. Moreover, we demonstrate that this test is sensitive to sickling therapies that increase the production of fetal Hb. This viscosity-based measurement thus offers the prospect of an assay that is 10 times faster than any current test of which we are aware, at costs that rival the least expensive of any current assays.
Producing Human Amniotic Epithelial Cells-only Membrane for Transplantation
Authors: Xu Chenze , Ahmed Waqas , Xie Lili , Peng Yan , Wang Qizheng , Guo Meijin 
Published: November 2019

AbstractHuman amniotic epithelial cells (hAECs), as pluripotent stem cells, have characteristics of immune privilege and great clinical potential. Here, we produced hAECs membrane consisting of single-layer hAECs and basal membrane (BM) of human amniotic membrane (hAM). In conventional methods, hAECs were isolated from hAM by repeated trypsin digestion. In this study, collagenase I and cell scraper were used to remove human amniotic mesenchymal stem cells (hAMSCs) from hAM and hAECs-only membranes were produced. These hAECs on the membranes were evaluated by surface biomarkers including epithelial cell adhesion molecule (EpCAM), stage-specific embryonic antigen 4 (SSEA4) and endoglin (CD105), transcriptional level of biomarkers including POU class 5 homeobox 1 (OCT4), sex determining region Y-box 2 (SOX2), fibroblast growth factor 4 (FGF4), immunofluorescence of cytokeratin-8 (CK-8), alpha smooth muscle actin (α-SMA) and collagen type I alpha 1 chain (ColA1). Finally, the hAECs membrane were transplanted on skin-removed mice to evaluate its effect on wound healing. In comparison to the hAECs isolated by the conventional methods, the cells isolated by this proposed method had higher purity of hAECs, expressed higher in pluripotency related genes, and maintained an epithelium construction in a long-term culture. In mice application, the hAECs membrane effectively improved the skin wound healing. An efficient method was successfully established to produce hAECs membrane in this work which not only held promise to obtain hAECs in higher purity and quality, but also showed practical clinical potential.
De novo transcriptome sequence of Senna tora provides insights into anthraquinone biosynthesis
Authors: Kang Sang-Ho , Lee Woo-Haeng , Lee Chang-Muk , Sim Joon-Soo , Won So Youn , Han So-Ra , Kwon Soo-Jin , Kim Jung Sun , Kim Chang-Kug , Oh Tae-Jin 
Published: November 2019

AbstractSenna tora is an annual herb with rich source of anthraquinones that have tremendous pharmacological properties. However, there is little mention of genetic information for this species, especially regarding the biosynthetic pathways of anthraquinones. To understand the key genes and regulatory mechanism of anthraquinone biosynthesis pathways, we performed spatial and temporal transcriptome sequencing of S. tora using short RNA sequencing (RNA-Seq) and long-read isoform sequencing (Iso-Seq) technologies, and generated two unigene sets composed of 118,635 and 39,364, respectively. A comprehensive functional annotation and classification with multiple public databases identified array of genes involved in major secondary metabolite biosynthesis pathways and important transcription factor (TF) families (MYB, MYB-related, AP2/ERF, C2C2-YABBY, and bHLH). Differential expression analysis indicated that the expression level of genes involved in anthraquinone biosynthetic pathway regulates differently depending on the degree of tissues and seeds development. Furthermore, we identified that the amount of anthraquinone compounds were greater in late seeds than early ones. In conclusion, these results provide a rich resource for understanding the anthraquinone metabolism in S. tora.
Semaphorin 3a reduces the side effects of radiation on BMSCs by reducing ROS
Authors: Huang Bo , Tang Haiyang , He Tao , Yang Zheng , Gong Ping 
Published: November 2019

1.AbstractBackground/AimsRadiotherapy does not only kill tumor cells but also impairs the function of adjacent tissues, especially bone metabolism by damaging bone marrow stromal stem cells (BMSCs). This study aimed to investigate the effect of semaphorin 3a (Sema3a) on BMSCs exposed to 2 Gy radiation.MaterialsBMSCs were divided into four groups, namely, group A (0 Gy), group B (2 Gy), group C (0 Gy + Sema3a), and group D (2 Gy + Sema3a). A Cell Counting Kit-8 kit, Alizarin-Red and Oil-Red-O staining, alkaline phosphatase activity kit, and dichlorodihydro-fluoresce in diacetate were used to test cell proliferation, cell cycle, osteogenic ability, adipogenic ability, and the level of reactive oxygen species (ROS), respectively, in each group. Real-time PCR was performed to test the expression of osteogenic (osteocalcin and Runt-related transcription factor 2), adipogenic (peroxisome proliferator-activated receptor gamma), interleukin (IL)-6, and tumor necrosis factor (TNF)-α genes.ResultsBMSC proliferation, osteogenic differentiation, and the number of cells undergoing division (S+G2 phase of the cell cycle) were found to be lower in group B than in group A. and the cellular levels of ROS, adipogenic differentiation, and expression of inflammatory factors (IL-6 and TNF-α) were higher in group B than in group A. Furthermore, osteogenic differentiation ability was higher in group D than in group B, and adipogenic differentiation ability, cellular levels of ROS, and gene expression of TNF-α and IL-6 were lower in group D than in group B.ConclusionThis study demonstrated that 2 Gy radiation could decrease the osteogenic differentiation ability of BMSCs and increase their adipogenic differentiation ability by increasing the production of ROS. However, Sema3a could reduce these side effects by decreasing the levels of ROS.
Multiplexed direct detection of barcoded protein reporters on a nanopore array
Authors: Cardozo Nicolas , Zhang Karen , Doroschak Katie , Nguyen Aerilynn , Siddiqui Zoheb , Strauss Karin , Ceze Luis , Nivala Jeff 
Published: November 2019

AbstractGenetically encoded reporter proteins are a cornerstone of molecular biology. While they are widely used to measure many biological activities, the current number of uniquely addressable reporters that can be used together for one-pot multiplexed tracking is small due to overlapping detection channels such as fluorescence. To address this, we built an expanded library of orthogonally-barcoded Nanopore-addressable protein Tags Engineered as Reporters (NanoporeTERs), which can be read and demuxed by nanopore sensors at the single-molecule level. By adapting a commercially available nanopore sensor array platform typically used for real-time DNA and RNA sequencing (Oxford Nanopore Technologies’ MinION), we show direct detection of NanoporeTER expression levels from unprocessed bacterial culture with no specialized sample preparation. These results lay the foundations for a new class of reporter proteins to enable multiplexed, real-time tracking of gene expression with nascent nanopore sensor technology.