bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variation ofAedes aegyptipopulations from Ecuador
Authors: Cevallos Varsovia , Benítez Denisse , Coloma Josefina , Carrazco Andrés , Wang Chunling , Holecheck Susan , Quiroga Cristina , Castillo Gabriela , Tillis Britney , Ponce Patricio 
Published: December 2019

AbstractThis is the first genetic analysis in Ecuador ofAedes aegyptiusing fragments of mitochondrial genes, NADH dehydrogenase subunit 4 (ND4) and cytochrome oxidase subunit I (COI). A total of 154 mosquitoes from 23 localities were collected in the Pacific coastal lowlands, Amazon basin lowlands, and the Galápagos Islands from 2012 to 2019. The analysis of fragments of the genes COI (672 bp) and ND4 (262 bp) and concatenated analysis of both COI and ND4 showed two haplotypes (H1, H2) present in Ecuador mainland and the Galápagos Islands. The phylogenetic analysis identified two well-supported clades. Combined analysis of both genes from ten localities also resulted in two haplotypes. Nucleotide diversity, neutrality tests (Tajima’s test D, Fu and Li’s F*and D*) and AMOVA analysis of the entire data set suggest balancing selection for both genes. The results indicate genetic variation without geographical restriction. COI-H1 grouped with sequences from the Americas, West and Central Africa, East Africa, Asia, and Australia. ND4-H1 grouped with similar sequences from the Americas, Asia and West Africa. COI-H2 grouped with sequences from Asia and the Americas. ND4-H2 grouped with sequences from the Americas. We report overlapping peaks in four sequences that suggest heteroplasmy in the individuals. The origin of the populations ofAedes aegyptiin Ecuador show African genetic origin and are widely present in several countries in the Americas. One of the genetic variants is more common in all the localities and the two haplotypes are distributed indistinctly in the three geographical sampled areas in Ecuador.
Bacterial killing by complement requires direct anchoring of Membrane Attack Complex precursor C5b-7
Authors: Doorduijn Dennis J , Bardoel Bart W , Heesterbeek Dani AC , Ruyken Maartje , Benn Georgina , Parsons Edward S , Hoogenboom Bart , Rooijakkers Suzan HM 
Published: December 2019

AbstractAn important effector function of the human complement system is to directly kill Gram-negative bacteria via Membrane Attack Complex (MAC) pores. MAC pores are assembled when surface-bound convertase enzymes convert C5 into C5b, which together with C6, C7, C8 and multiple copies of C9 forms a transmembrane pore that damages the bacterial cell envelope. Recently, we found that bacterial killing by MAC pores requires local conversion of C5 by surface-bound convertases. In this study we aimed to understand why local assembly of MAC pores is essential for bacterial killing. Here, we show that rapid interaction of C7 with C5b6 is required to form bactericidal MAC pores. Binding experiments with fluorescently labelled C6 show that C7 prevents release of C5b6 from the bacterial surface. Moreover, trypsin shaving experiments and atomic force microscopy revealed that this rapid interaction between C7 and C5b6 is crucial to efficiently anchor C5b-7 to the bacterial cell envelope and form complete MAC pores. Using complement-resistant clinicalE. colistrains, we show that bacterial pathogens can prevent complement-dependent killing by interfering with the anchoring of C5b-7. While C5 convertase assembly was unaffected, these resistant strains blocked efficient anchoring of C5b-7 and thus prevented stable insertion of MAC pores into the bacterial cell envelope. Altogether, these findings provide basic molecular insights into how bactericidal MAC pores are assembled and how bacteria evade MAC-dependent killing.
Structural and functional characterization of oligomeric states of proteins in RecFOR pathway
Authors: Chaudhary Santosh Kumar , Elayappan Mohanapriya , Jeyakanthan Jeyaraman , Sekar Kanagaraj 
Published: December 2019

AbstractRecFOR pathway is the principal repair pathway for double strand break and single strand gap repair inThermus thermophilus. RecF and RecR exist as monomer and dimer in solution, interestingly; they undergo condition-dependent dimerization and tetramerization, respectively during the DNA break repair. However, their importance in protein-protein and protein-DNA interactions remains elusive. In this study, the three-dimensional crystal structures of the wild type RecF and RecR proteins are determined. Thereafter, the structural information is used to mutate the interface residues to cysteine to stabilize the dimeric and tetrameric states of the RecF and RecR proteins, respectively. A comparative study for their interactions with other cognate proteins and ssDNA in native and SSB (single strand binding protein) bound states was performed. RecF or RecFR complex displays a negligible affinity towards ssDNA. Conversely, the RecF mutants and its complexes with wild type RecR showed affinity towards ssDNA, suggesting, distinct modes of interaction of RecF and RecFR complex for ssDNA binding. In the presence of RecO, the stabilized tetrameric RecR showed a lower binding affinity for ssDNA as compared to the SSB bound ssDNA, indicating the importance of tetrameric RecR in stabilizing the RecOR complex on the SSB coated ssDNA. This provides an insight into the reduction of the binding affinity of SSB proteins with the ssDNA, which in turn enhances the recruitment of RecA for strand exchange.
The Tung Tree (Vernicia Fordii) Genome Provides A Resource for Understanding Genome Evolution and Oil Improvement
Authors: Zhang Lin , Liu Meilan , Long Hongxu , Dong Wei , Pasha Asher , Esteban Eddi , Li Wenying , Yang Xiaoming , Li Ze , Song Aixia , Ran Duo , Zhao Guang , Zeng Yanling , Chen Hao , Zou Ming , Li Jingjing , Liang Fan , Xie Meili , Hu Jiang , Wang Depeng , Cao Heping , Provart Nicholas J. , Zhang Liangsheng , Tan Xiaofeng 
Published: December 2019

AbstractTung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil containing a high proportion of eleostearic acid (∼80%). Here we report a high-quality, chromosome-scale tung tree genome sequence of 1.12 Gb with 28,422 predicted genes and over 73% repeat sequences. Tung tree genome was assembled by combining Illumina short reads, PacBio single-molecule real-time long reads and Hi-C sequencing data. Insertion time analysis revealed that the repeat-driven tung tree genome expansion might be due to long standing long terminal repeat (LTR) retrotransposon bursts and lack of efficient DNA deletion mechanisms. An electronic fluorescent pictographic (eFP) browser was generated based on genomic and RNA-seq data from 17 various tissues and developmental stages. We identified 88 nucleotide-binding site (NBS)-encoding resistance genes, of which 17 genes may help the tung tree resist theFusariumwilt shortly after infection. A total of 651 oil-related genes were identified and 88 of them were predicted to be directly involved in tung oil biosynthesis. The fewer phosphoenolpyruvate carboxykinase (PEPC) genes, and synergistic effects between transcription factors and oil biosynthesis-related genes may contribute to high oil content in tung seeds. The tung tree genome should provide valuable resources for molecular breeding and genetic improvement.
Use of thep-valueas a size-dependent function to address practical differences when analyzing large datasets
Authors: Gómez-de-Mariscal Estibaliz , Guerrero Vanesa , Sneider Alexandra , Jayatilaka Hasini , Phillip Jude M. , Wirtz Denis , Muñoz-Barrutia Arrate 
Published: December 2019

ABSTRACTBiomedical research has come to rely onp-valuesas a deterministic measure for data-driven decision making. In the largely extended null-hypothesis significance testing (NHST) for identifying statistically significant differences among groups of observations, a singlep-valuecomputed from sample data is routinely compared with a threshold, commonly set to 0.05, to assess the evidence against the hypothesis of having non-significant differences among groups, or the null hypothesis. Because the estimatedp-valuetends to decrease when the sample size is increased, applying this methodology to large datasets results in the rejection of the null hypothesis, making it not directly applicable in this specific situation. Herein, we propose a systematic and easy-to-follow method to detect differences based on the dependence of thep-valueon the sample size. The proposed method introduces new descriptive parameters that overcome the effect of the size in thep-valueinterpretation in the framework of large datasets, reducing the uncertainty in the decision about the existence of biological/clinical differences between the compared experiments. This methodology enables both the graphical and quantitative characterization of the differences between the compared experiments guiding the researchers in the decision process. An in-depth study of the proposed methodology is carried out using both simulated and experimentally obtained data. Simulations show that under controlled data, our assumptions on thep-valuedependence on the sample size holds. The results of our analysis in the experimental datasets reflect the large scope of this approach and its interpretability in terms of common decision-making and data characterization tasks. For both simulated and real data, the obtained results are robust to sampling variations within the dataset.
Quantifying the impact of an inference model in Bayesian phylogenetics
Authors: Bilderbeek Richèl J.C. , Laudanno Giovanni , Etienne Rampal S. 
Published: December 2019

SummaryPhylogenetic trees are currently routinely reconstructed from an alignment of character sequences (usually nucleotide sequences). Bayesian tools, such as MrBayes, RevBayes and BEAST2, have gained much popularity over the last decade, as they allow joint estimation of the posterior distribution of the phylogenetic trees and the parameters of the underlying inference model. An important ingredient of these Bayesian approaches is the species tree prior. In principle, the Bayesian framework allows for comparing different tree priors, which may elucidate the macroevolutionary processes underlying the species tree. In practice, however, only macroevolutionary models that allow for fast computation of the prior probability are used. The question is how accurate the tree estimation is when the real macroevolutionary processes are substantially different from those assumed in the tree prior.Here we presentpirouette, a free and open-source R package that assesses the inference error made by Bayesian phylogenetics for a given macroevolutionary diversification model.pirouettemakes use of BEAST2, but its philosophy applies to any Bayesian phylogenetic inference tool.We describepirouette’s usage providing full examples in which we interrogate a model for its power to describe another.Last, we discuss the results obtained by the examples and their interpretation.
LAVA: a streamlined visualization tool for longitudinal analysis of viral alleles
Authors: Lin Michelle J. , Shean Ryan C. , Makhsous Negar , Greninger Alexander L. 
Published: December 2019

AbstractWith their small genomes, fast evolutionary rates, and clinical significance, viruses have long been fodder for studies of whole genome evolution. One common need in these studies is the analysis of viral evolution over time through longitudinal sampling. However, there exists no simple tool to automate such analyses. We created a simple command-line visualization tool called LAVA (Longitudinal Analysis of Viral Alleles). LAVA allows dynamic and interactive visualization of viral evolution across the genome and over time. Results are easily shared via a single HTML file that also allows interactive analysis based on read depth and allele frequency. LAVA requires minimal input and runs in minutes for most use cases. LAVA is programmed mainly in Python 3 and is compatible with Mac and Linux machines. LAVA is a user-friendly command-line tool for generating, visualizing, and sharing the results of longitudinal viral genome evolution analysis. Instructions for downloading, installing, and using LAVA can be found at https://github.com/michellejlin/lava.
Intelli-NGS: Intelligent NGS, a deep neural network-based artificial intelligence to delineate good and bad variant calls from IonTorrent sequencer data
Authors: Singh Aditya , Bhatia Prateek 
Published: December 2019

AbstractBackgroundIonTorrent is a second-generation sequencing platform with smaller capital costs than Illumina but is also prone to higher machine error than later. Given its lower costs, the platform is generally preferred in developing countries where next-generation sequencing is still a very exclusive technique. There are many software tools available for other platforms but IonTorrent. This makes the already tricky analysis part more error-prone.MotivationWe have been using the IonTorrent platform in our hospital setting for aiding diagnosis or treatment for the past couple of years. Given to our experience, analysis part of IonTorrent data takes the longest time and still, we used to get stuck with certain variants which seemed fine on looking at their metrics but were found to be negative in Sanger sequencing verification. This made us determined to develop a tool that could aid us in reducing false positive and negative rates while still retaining good recall. The artificial intelligence-based technique was our final choice after developing pipelines with less success.MethodologyThe artificial intelligence was developed from scratch in Python 3 using TensorFlow fully connected dense layers. The model takes VCF files as input and solves each variant based on the thirty-five parameters given by the IonTorrent platform, including the flow-space information which is missed by variant callers other than the default torrent variant caller.ResultsThe final trained model was able to achieve an accuracy of 93.08% and a ROC-AUC of 0.95 with GIAB validation data. The additional program that was written to run the model annotates each variant using online databases such as dbSNP, ClinVar and others. A probability score for each outcome for each variant is also provided to aid in decision making.AvailabilityThe model and running code are available for free only for non-commercial users athttps://www.github.com/aditya-88/intelli-ngs.
Transcriptional regulation of MGE progenitor proliferation by PRDM16 controls cortical GABAergic interneuron production
Authors: García Miguel Turrero , Baizabal José-Manuel , Tran Diana , Peixoto Rui , Wang Wengang , Xie Yajun , Adam Manal A. , Brito Salvador , Booker Matthew A. , Tolstorukov Michael Y. , Harwell Corey C. 
Published: December 2019

SUMMARYThe mammalian cortex is populated by neurons derived from neural progenitors located throughout the embryonic telencephalon. Excitatory neurons are derived from progenitors located in the dorsal telencephalon, while inhibitory interneurons are generated by ventral telencephalic progenitors. The transcriptional regulator PRDM16 is expressed by radial glia, neural progenitors present in both regions; however, its mechanisms of action are still not fully understood. It is unclear if PRDM16 functions plays a role in neurogenesis in both dorsal and ventral progenitor lineages, and if so, whether it does so by regulating common or unique networks of genes. Here, we show thatPrdm16expression in MGE progenitors is required for maintaining their proliferative capacity and for the production of proper numbers of pallial GABAergic interneurons. PRDM16 binds to cis-regulatory elements and represses the expression of region-specific neuronal differentiation genes, thereby controlling the timing of neuronal maturation. Our results highlight the importance of PRDM16 for the development of both excitatory and inhibitory cortical circuits. We demonstrate the existence of convergent developmental gene expression programs regulated by PRDM16, which utilize both common and region-specific sets of genes in the cortex and the MGE to control the proliferative capacity of neural progenitors, ensuring the generation of correct numbers of cortical neurons.
Management of a Walnut Germplasm Collection: Which of SSR or SNP Markers Are Most Suitable to Preserve Biodiversity?
Authors: Bernard Anthony , Barreneche Teresa , Donkpegan Armel , Fabrice Lheureux , Dirlewanger Elisabeth 
Published: December 2019

AbstractThe preservation of the maximum of diversity within the smallest number of accessions is one of the challenges of germplasm management. To construct core-collections, the assessment of the population structure and the relationships between the accessions represents a key step and the choice of suitable molecular markers is the starting point. Since the expansion of available SNP-based genomics tools, a debate has emerged regarding the usefulness of the widely used microsatellites (SSRs) markers. In this study, we analysed a part of the INRAE walnut germplasm collection of 150 accessions, unique in Europe for walnut biodiversity conservation, by comparing the power of both types of marker. We found that the first level of structure is equally detected using 13 SSRs or the Axiom™J. regia700K SNP array, and is in relation with the geographical origin of the accessions. For K=2, there was no exchange of accession between the two groups when both markers were compared. We also highlighted empirically that approximately 100 SNPs are needed to obtain similar clustering to SSRs in Principal Coordinate Analysis (PCoA). The neighbor-joining trees constructed were also consistent between both types of marker. The main differences lied in the upper levels of structure from K=3 to K=6, more powerful using the SNPs, and in the percentage of the explained variation in PCoA for K=2, higher using SSRs. We then constructed core-collections of 50 accessions, a crucial step in genetic resources management to reduce the costs and preserve the allelic diversity. Using two different construction methods, both SSR and SNP markers were suitable and able to keep at least 88.57% of the alleles. 32/50 accessions were in common between the two markers, for both methods. We concluded that the use of either marker is dependent on the researcher’s goal.
Antioxidant, anti-enzymatic, antimicrobial and cytotoxic properties ofEuphorbia tirucalliL
Authors: Altamimi Mohammad , Jaradat Nidal , Alham Saad , Al-Masri Motasem , Bsharat Ala , Alsaleh Rania , Sabobeh Rozan 
Published: December 2019

AbstractMedicinal properties ofEuphorbia tirucalliL. have been investigated in vitro. Water extract from the plant latex was freeze dried and tested against 3 digestive enzymes and showed IC50 as 39.8±0.22, 79.43±0.38 and 316.22±0.3 for lipase, alpha- glucosidase and alpha- amylase, respectively. These results were incomparable with drugs such as acarbose and orlistat. Antioxidant property showed that the IC50 values ofE. tirucalliand Trolox were 79.43±0.69 and 3.1 ±0.92 respectively. Also, the plant extract exhibited a range of antimicrobial activity against gram-positive and gram-negative bacteria and pathogenic yeast and fungi. Cytotoxicity of the plant extract tested on Caco-2 cells was determined using MTT method. The effect was linear and almost 0.5 mg/ml extract has inhibited 50% of cells relative to the control.Euphorbia tirucallishowed promising activities and is potential source of active ingredient with functional properties.
Evolution of the insecticide targetRdlin AfricanAnophelesis driven by interspecific and interkaryotypic introgression
Authors: Grau-Bové Xavier , Tomlinson Sean , O’Reilly Andrias O. , Harding Nicholas J. , Miles Alistair , Kwiatkowski Dominic , Donnelly Martin J. , Weetman David ,   The Anopheles gambiae 1000 Genomes Consortium
Published: December 2019

AbstractThe evolution of insecticide resistance mechanisms in natural populations ofAnophelesmalaria vectors is a major public health concern across Africa. Using genome sequence data, we study the evolution of resistance mutations in theresistance to dieldrin locus(Rdl), a GABA receptor targeted by several insecticides, but most notably by the long-discontinued cyclodiene, dieldrin. The twoRdlresistance mutations (296Gand296S) spread across West and Central AfricanAnophelesvia two independent hard selective sweeps that included likely compensatory nearby mutations, and were followed by a rare combination of introgression across species (fromA. gambiaeandA. arabiensistoA. coluzzii) and across non-concordant karyotypes of the 2La chromosomal inversion.Rdlresistance evolved in the 1950s as the first known adaptation to a large-scale insecticide-based intervention, but the evolutionary lessons from this system highlight contemporary and future dangers for management strategies designed to combat development of resistance in malaria vectors.
A polarized nucleus-cytoskeleton-ECM connection controls collective migration and cardioblasts number inDrosophila
Authors: Dondi C , Bertin B , Da Ponte JP , Wojtowicz I , Jagla K , Junion G 
Published: December 2019

AbstractThe formation of the cardiac tube is a remarkable example of complex morphogenetic process conserved from invertebrates to humans. It involves coordinated collective migration of contralateral rows of cardiac cells. The molecular processes underlying the specification of cardioblasts prior to migration are well established and significant advances have been made in understanding the process of lumen formation. However, the mechanisms of collective cardiac cells migration remain elusive. Here we identifiedCAPandMSP-300as novel actors involved in cardioblast migration. They both display highly similar temporal and spatial expression pattern in migrating cardiac cells and are required for the correct number, alignment and coordinated directional migration of cardioblasts. Our data suggest that CAP and MSP-300 are part of a tension-sensitive protein complex linking cardioblast focal adhesion sites to nuclei via actin cytoskeleton and triggering coordinated cardioblast movements.
Visualizing ’omic feature rankings and log-ratios using Qurro
Authors: Fedarko Marcus W. , Martino Cameron , Morton James T. , González Antonio , Rahman Gibraan , Marotz Clarisse A. , Minich Jeremiah J. , Allen Eric E. , Knight Rob 
Published: December 2019

AbstractMany tools for dealing with compositional “’omics” data produce feature-wise values that can be ranked in order to describe features’ associations with some sort of variation. These values include differentials (which describe features’ associations with specified covariates) and feature loadings (which describe features’ associations with variation along a given axis in a biplot). Although prior work has discussed the use of these “rankings” as a starting point for exploring the log-ratios of particularly high-or low-ranked features, such exploratory analyses have previously been done using custom code to visualize feature rankings and the log-ratios of interest. This approach is laborious, prone to errors, and raises questions about reproducibility. To address these problems we introduce Qurro, a tool that interactively visualizes a plot of feature rankings (a “rank plot”) alongside a plot of selected features’ log-ratios within samples (a “sample plot”). Qurro’s interface includes various controls that allow users to select features from along the rank plot to compute a log-ratio; this action updates both the rank plot (through highlighting selected features) and the sample plot (through displaying the current log-ratios of samples). Here we demonstrate how this unique interface helps users explore feature rankings and log-ratios simply and effectively.