bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inferring the landscape of recombination using recurrent neural networks
Authors: Adrion Jeffrey R. , Galloway Jared G. , Kern Andrew D. 
Published: June 2019

AbstractAccurately inferring the genome-wide landscape of recombination rates in natural populations is a central aim in genomics, as patterns of linkage influence everything from genetic mapping to understanding evolutionary history. Here we describe ReLERNN, a deep learning method for estimating a genome-wide recombination map that is accurate even with small numbers of pooled or individually sequenced genomes. Rather than use summaries of linkage disequilibrium as its input, ReLERNN takes columns from a genotype alignment, which are then modeled as a sequence across the genome using a recurrent neural network. We demonstrate that ReLERNN improves accuracy and reduces bias relative to existing methods and maintains high accuracy in the face of demographic model misspecification, missing genotype calls, and genome inaccessibility. We apply ReLERNN to natural populations of AfricanDrosophila melanogasterand show that genome-wide recombination landscapes, while largely correlated among populations, exhibit important population-specific differences. Lastly, we connect the inferred patterns of recombination with the frequencies of major inversions segregating in naturalDrosophilapopulations.
A Bayesian Framework for Detecting Gene Expression Outliers in Individual Samples
Authors: Vivian John , Eizenga Jordan , Beale Holly C. , Morozova-Vaske Olena , Paten Benedict 
Published: June 2019

ABSTRACTObjectiveMany antineoplastics are designed to target upregulated genes, but quantifying upregulation in a single patient sample requires an appropriate set of samples for comparison. In cancer, the most natural comparison set is unaffected samples from the matching tissue, but there are often too few available unaffected samples to overcome high inter-sample variance. Moreover, some cancer samples have misidentified tissues or origin, or even composite-tissue phenotypes. Even if an appropriate comparison set can be identified, most differential expression tools are not designed to accommodate comparing to a single patient sample.Materials and MethodsWe propose a Bayesian statistical framework for gene expression outlier detection in single samples. Our method uses all available data to produce a consensus background distribution for each gene of interest without requiring the researcher to manually select a comparison set. The consensus distribution can then be used to quantify over- and under-expression.ResultsWe demonstrate this method on both simulated and real gene expression data. We show that it can robustly quantify overexpression, even when the set of comparison samples lacks ideally matched tissues samples. Further, our results show that the method can identify appropriate comparison sets from samples of mixed lineage and rediscover numerous known gene-cancer expression patterns.ConclusionsThis exploratory method is suitable for identifying expression outliers from comparative RNA-seq analysis for individual samples and Treehouse, a pediatric precision medicine group that leverages RNA-seq to identify potential therapeutic leads for patients, plans to explore this method for processing their pediatric cohort.
High risk of the Fall Armyworm invading into Japan and the Korean Peninsula via overseas migration
Authors: Ma Jian , Wang Yun-Ping , Wu Ming-Fei , Gao Bo-Ya , Liu Jie , Lee Gwan-Seok , Otuka Akira , Hu Gao 
Published: June 2019

AbstractThe fall armyworm, Spodoptera frugiperda (J.E. Smith) is an emerging and most severe pest species in the Old World. It is originally native in the Americas. Since 2016 it has spread widely and rapidly to throughout Africa, the Middle East, India, Southeast Asia and most recently southern China. By May 2019 it has appeared in 13 provinces in most southern China and would spread further to northern China. It is highly likely that S. frugiperda would enter into Japan and Korea via overseas migrations as many other migratory pests did before. To evaluate the invasion risk of S. frugiperda into Japan and Korean Peninsula, we modelled the rate of expansion and future potential migratory range of the insect by a trajectory analytical approach with flight behaviour of S. frugiperda implemented, and meteorological data of past five years (2014–2018) used. Our results predicted that S. frugiperda would migrate from southern and eastern China into Japan and Korea soon. Most likely, Japan would be invaded from Fujian and Zhejiang on 1 June – 15 July, and Kyushu, Shikoku and south-western Honshu could face the highest risk of S. frugiperda’s invasion. Korea would be most possibly reached by S. frugiperda from northern Zhejiang, Jiangsu, Anhui, and Shandong on 1 June – 15 July and later. Our results indicated a very high risk that S. frugiperda would annually invade Japan and the Korean Peninsula and cause a possible significant decrease in agricultural productivity.
Inactivation of genes in oxidative respiration and iron acquisition pathways in pediatric clinical isolates of small-colony variantEnterobactericeae
Authors: Greninger Alexander L. , Addetia Amin , Tao Yue , Adler Amanda , Qin Xuan 
Published: June 2019

AbstractIsolation of bacterial small colony variants (SCVs) from clinical specimens is not uncommon and can fundamentally change the outcome of the associated infections. Bacterial SCVs often emerge with their normal colony phenotype (NCV) co-isolates in the same sample. The genetic and biochemical basis of SCV emergencein vivois not well understood in Gram-negative bacteria. In this study, we interrogated the causal genetic lesions of SCV growth in three pairs of NCV and SCV co-isolates ofEscherichia coli, Citrobacter freundii, andEnterobacter hormaechei. We confirmed the isogenic basis of SCV emergence, as there were only 4 single nucleotide variants in SCV forE. coli, 5 inC. freundii, and 8 inE. hormaechei, with respect to their NCV co-isolate. In addition, a 10.2kb chromosomal segment containing 11 genes was deleted in theE. hormaecheiSCV isolate. Intriguingly, each SCV had at least one coding change in a gene associated with bacterial oxidative respiration and another involved iron capture. Chemical rescue confirmed the causal role of heme biosynthesis inE. coliandC. freundiiand lipoic acid inE. hormaecheiSCV isolates. Genetic rescue restored normal growth under aerobic conditions forfesandhemLinC. freundii;hemLinE. coli; andlipAinE. hormaecheiSCV isolates. Prototrophic growth in all 3 SCVEnterobacteriaceaespecies was unaffected under anaerobic culture conditionsin vitro, illustrating how SCVs may persistin vivoby abandoning the highly energetic lifestyle in an iron-limiting environment. We propose that the selective loss of functions in oxidative respiration and iron acquisition is indicative of bacterial virulence attenuation for niche specialization and persistencein vivo.ImportanceSmall colony variant (SCV) bacteria are routinely isolated in the clinical microbiology laboratory and can be notoriously difficult to treat. Most studies of the genetic underpinnings of SCV clinical isolates have examinedStaphylococcus aureusand few have looked at how SCV emerge in Gram-negative bacteria. Here, we undertook detailed characterization of three clinical isolates of SCV inEscherichia coli, Citrobacter freundii, andEnterobacter hormaecheialong with their NCV co-isolates. Genomic sequencing revealed that each SCV had at least one coding change in genes involved in both bacterial oxidative respiration and iron capture. Chemical and genetic rescue revealed that both pathways could be responsible for the small colony variant. Each of the SCV showed no growth defect compared to NCV when incubated under anaerobic conditions, indicating a potential mechanism for SCV survivalin vivo. We hypothesize that by retreating to anaerobic environments and avoiding escalating iron competition with the host, SCV have adapted to live to see another day.
CX3CL1 binding protein-2 (CBP2) of Plasmodium falciparum binds nucleic acids
Authors: Saxena Ritu , Kaur Jasweer , Hora Rachna , Singh Palwinder , Singh Vineeta , Mishra Prakash Chandra 
Published: June 2019

AbstractSeveral exported Plasmodium falciparum(Pf) proteins contribute to malaria biology through their involvement in cytoadherence, immune evasion and host cell remodelling. Many of these exported proteins and other host molecules are present in iRBC (infected red blood cell) generated extracellular vesicles (EVs), which are responsible for host cell modification and parasite development. CX3CL1 binding proteins (CBPs) present on the surface of iRBC have been reported to contribute to cytoadhesion by binding with the chemokine ‘CX3CL1’ via their extracellular domains. Here, we have characterized the cytoplasmic domain of CBP2to understand its function in parasite biology using biochemical and biophysical methods. Recombinant cytoplasmic CBP2 (rcCBP2) binds nucleic acids showing interaction with DNA/RNA. rcCBP2 shows dimer formation under non-reducing conditions highlighting the role of disulphide bonds in oligomerization while ATP binding leads to structural changes in the protein. In vitro interaction studies depict its binding with a Maurer’s cleft resident protein ‘PfSBP1’, which is influenced by ATP binding of rcCBP2. Our results suggest CBP2 as a two-transmembrane (2TM) receptor responsible for targeting EVs and delivering cargo to host endothelial cells. We propose CBP2 as an important molecule having roles in cytoadherence and immune modulation through its extracellular and cytoplasmic domains respectively.
Quantitative modeling links in vivo microstructural and macrofunctional organization of human and macaque insular cortex, and predicts cognitive control abilities
Authors: Menon Vinod , Guillermo Gallardo , Pinsk Mark A. , Nguyen Van-Dang , Li Jing-Rebecca , Cai Weidong , Wassermann Demian 
Published: June 2019

AbstractThe human insular cortex is a heterogenous brain structure which plays an integrative role in guiding behavior. The cytoarchitectonic organization of the human insula has been investigated over the last century using postmortem brains but there has been little progress in noninvasive in vivo mapping of its microstructure and large-scale functional circuitry. Quantitative modeling of multi-shell diffusion MRI (dMRI) data from 440 HCP participants revealed that human insula microstructure differs significantly across its functionally defined dorsal anterior, ventral anterior, and posterior insula subdivisions that serve distinct cognitive and affective functions. The microstructural organization of the insula was mirrored in its functionally interconnected circuits with the anterior cingulate cortex that anchor the salience network, a system important for adaptive switching of cognitive control systems. Novel validation of the human insula findings came from quantitative dMRI modeling in macaques which revealed microstructural features consistent with known primate insula cytoarchitecture. Theoretical analysis and computer simulations, using realistic 3-dimensional models of neuronal morphology from postmortem tissue, demonstrated that dMRI signals reflect the cellular organization of cortical gray matter, and that these signals are sensitive to cell size and the presence of large neurons such as the von Economo neurons. Crucially, insular microstructural features were linked to behavior and predicted individual differences in cognitive control ability. Our findings open new possibilities for probing psychiatric and neurological disorders impacted by insular cortex dysfunction, including autism, schizophrenia, and fronto-temporal dementia.Statement of SignificanceThe human insular cortex is a heterogenous brain structure which plays an integrative role in identifying salient sensory, affective, and cognitive cues for guiding attention and behavior. It is also is one of the most widely activated brain regions in all of human neuroimaging research. Here we use novel quantitative tools with in vivo diffusion MRI in large group (N=440) of individuals to uncover several unique microstructural features of the human insula and its macrofunctional circuits. Crucially, microstructural properties of the insular cortex predicted human cognitive control abilities, in agreement with its crucial role in adaptive human behaviors. Our findings open new possibilities for probing psychiatric and neurological disorders impacted by insular dysfunction, including autism, schizophrenia, and fronto-temporal dementia.
CA-170 – a potent small-molecule PD-L1 inhibitor or not?
Authors: Musielak Bogdan , Kocik Justyna , Skalniak Lukasz , Magiera-Mularz Katarzyna , Sala Dominik , Czub Mirosława , Holak Tad A. , Plewka Jacek 
Published: June 2019

AbstractCA-170is currently the only small-molecule modulator in clinical trials targeting PD-L1 and VISTA proteins – important negative checkpoint regulators of immune activation. The reported therapeutic results to some extent mimic those of FDA-approved monoclonal antibodies overcoming the limitations of the high production costs and adverse effects of the latter. However, no conclusive biophysical evidence proving the binding to hPD-L1 has ever been presented. Using well-knownin vitromethods: NMR binding assay, HTRF and cell-based activation assays, we clearly show that there is no direct binding betweenCA-170and PD-L1. To strengthen our reasoning, we performed control experiments onAUNP-12– a 29-mer peptide, which is a precursor ofCA-170. Positive controls consisted of the well-documented small-molecule PD-L1 inhibitors:BMS-1166and peptide p57.
Genome improvement and genetic map construction for Aethionema arabicum, the first divergent branch in the Brassicaceae family
Authors: Nguyen Thu-Phuong , Mühlich Cornelia , Mohammadin Setareh , van den Bergh Erik , Platts Adrian E. , Haas Fabian B. , Rensing Stefan A. , Schranz M. Eric 
Published: June 2019

AbstractBackgroundThe genus Aethionema is a sister-group to the core-group of the Brassicaceae family that includes Arabidopsis thaliana and the Brassica crops. Thus, Aethionema is phylogenetically well-placed for the investigation and understanding of genome and trait evolution across the family. We aimed to improve the quality of the reference genome draft version of the annual species Aethionema arabicum. Secondly, we constructed the first Ae. arabicum genetic map. The improved reference genome and genetic map enabled the development of each other.ResultsWe started with the initially published genome (version 2.5). PacBio and MinION sequencing together with genetic map v2.5 were incorporated to produce the new reference genome v3.0. The improved genome contains 203 MB of sequence, with approximately 94% of the assembly made up of called bases, assembled into 2,883 scaffolds. The N50 (10.3 MB) represents an 80-fold over the initial genome release. We generated a Recombinant Inbred Line (RIL) population that was derived from two ecotypes: Cyprus and Turkey (the reference genotype. Using a Genotyping by Sequencing (GBS) approach, we generated a high-density genetic map with 749 (v2.5) and then 632 SNPs (v3.0) was generated. The genetic map and reference genome were integrated, thus greatly improving the scaffolding of the reference genome into 11 linkage groups.ConclusionsWe show that long-read sequencing data and genetics are complementary, resulting in an improved genome assembly in Ae. arabicum. They will facilitate comparative genetic mapping work for the Brassicaceae family and are also valuable resources to investigate wide range of life history traits in Aethionema.
Predicting the Evolution of White Matter Hyperintensities in Brain MRI using Generative Adversarial Networks and Irregularity Map
Authors: Rachmadi Muhammad Febrian , Valdés-Hernández Maria del C. , Makin Stephen , Wardlaw Joanna M. , Komura Taku 
Published: June 2019

AbstractWe propose a Generative Adversarial Network (GAN) model named Disease Evolution Predictor GAN (DEP-GAN) to predict the evolution (i.e., progression and regression) of White Matter Hyperintensities (WMH) in small vessel disease. In this study, the evolution of WMH is represented by the “Disease Evolution Map” (DEM) produced by subtracting irregularity map (IM) images from two time points: baseline and follow-up. DEP-GAN uses two discriminators (critics) to enforce anatomically realistic follow-up image and DEM. To simulate the non-deterministic and unknown parameters involved in WMH evolution, we propose modulating an array of random noises to the DEP-GAN’s generator which forces the model to imitate a wider spectrum of alternatives in the results. Our study shows that the use of two critics and random noises modulation in the proposed DEP-GAN improves its performance predicting the evolution of WMH in small vessel disease. DEP-GAN is able to estimate WMH volume in the follow-up year with mean (std) estimation error of −1.91 (12.12)mland predict WMH evolution with mean rate of 72.01% accuracy (i.e., 88.69% and 23.92% better than Wasserstein GAN).
Serial position effects reflect the integrity of distinct brain regions in Major and Minor Neurocognitive Disorder
Authors: Foldi Nancy S. , Taylor Kirsten I. , Monsch Andreas U. , Sollberger Marc , Kivisaari Sasa L. 
Published: June 2019

ABSTRACTSerial Position Effects (SPE) in wordlist learning provide a rich set of metrics of cognitive functioning. In this study, we systematically mapped the neuroanatomical correlates of SPEs across delays in Major and Minor Neurocognitive disorders. Primacy, middle, and recency SPE scores of the California Verbal Learning Test at Learning, Short delay, and Long delay in healthy controls and patients with neurodegenerative disease were correlated with MRI gray matter signal intensities (voxel-based morphometry, VBM). The VBM analyses revealed distinct patterns of brain-behavioral correlations depending on both the SPE and the time-point. Unlike patients, the healthy controls’ performance incrementally improved recall of primacy items from Learning to Short and to Long delay, i.e., primacy progression. Moreover, the proportion of correct primacy items recalled at long delay compared to Learning correlated with bilateral medial temporal lobe regions, which commonly bear the brunt of pathology of Alzheimer’s disease. The results implicate the primacy progression score as an accessible and sensitive measure for disease detection, progression, and therapeutic response in Major and Minor Neurocognitive disorders.
Aimed Limb Movements in a Hemimetabolous Insect are Intrinsically Compensated for Allometric Wing Growth by Developmental Mechanisms
Authors: Patel Alexandra J. , Matheson Thomas 
Published: June 2019

ABSTRACTFor aimed limb movements to remain functional they must be adapted to developmental changes in body morphology and sensory-motor systems. Insects use their limbs to groom the body surface or to dislodge external stimuli, but they face the particular problem of adapting these movements to step-like changes in body morphology during metamorphosis or moulting. Locusts are hemimetabolous insects in which the imaginal moult to adulthood results in a sudden and dramatic allometric growth of the wings relative to the body and the legs. We show that, despite this, hind limb scratches aimed at mechanosensory stimuli on the wings remain targeted to appropriate locations after moulting. In juveniles, the tips of the wings extend less than half way along the abdomen, but in adults they extend well beyond the posterior end. Kinematic analyses were used to examine the scratching responses of juveniles (5thinstars) and adults to touch of anterior (wing base) and posterior (distal abdomen) targets that develop isometrically, and to wing tip targets that are anterior in juveniles but posterior in adults. Juveniles reach the (anterior) wing tip with the distal tibia of the hind leg using anterior rotation of the thoraco-coxal and coxo-trochanteral (‘hip’) joints and flexion of the femoro-tibial (‘knee’) joint. Adults, however, reach the corresponding (but now posterior) wing tip using posterior rotation of the hip and extension of the knee, reflecting a different underlying motor pattern. This change in kinematics occurs immediately after the adult moult without learning, indicating that the switch is developmentally programmed.SUMMARY STATEMENTA developmentally programmed change in the scratching movements of locusts permits adult animals to aim their movements at new wing tip targets, without learning.
Homogenization of Rhizosphere Bacterial Communities by Pea (Pisum sativum L.) Cultivated under Different Conservation Agricultural Practices in the Eastern Himalayas
Authors: Chaudhari Diptaraj , Rangappa Krishnappa , Das Anup , Layek Jayanta , Basavaraju Savita , Shouche Yogesh , Rahi Praveen 
Published: June 2019

AbstractConservation agriculture offers a suitable system to harmonize agriculture with the environment, especially in fragile ecosystems of North-East India. Soil microbes play pivotal roles in ecosystem functioning and act as indispensable indicators of overall fitness of crop plant and soil health. Here we demonstrated that altercations in residue management and tillage practices lead to the development of differential bacterial communities forcing the pea plants to recruit special groups of bacteria leading to highly homogenous rhizosphere communities. Pea rhizosphere and bulk soil samples were collected, and bacterial community structure was estimated by 16S rRNA gene amplicon sequencing and predictive functional analysis was performed using Tax4Fun. The effect on pea plants was evident in the bacterial communities as the overall diversity of rhizosphere samples was significantly higher to that of bulk soil samples. Bacillus, Staphylococcus, Planomicrobium, Enterobacter, Arthrobacter, Nitrobacter, Geobacter, and Sphingomonas were noticed as the most abundant genera in the rhizosphere and bulk soil samples. The abundance of Firmicutes and Proteobacteria altered significantly in the rhizosphere and bulk samples, which was further validated by qPCR. Selection of specific taxa by pea plant was indicated by the higher values of mean proportion of Rhizobium, Pseudomonas, Pantoea, Nitrobacter, Enterobacter and Sphingomonas in rhizosphere samples, and Massilia, Paenibacillus and Planomicrobium in bulk soil samples. Tillage and residue management treatments did not significantly alter the bacterial diversity, while their influence was observed on the abundance of few genera. Recorded results revealed that pea plant selects specific taxa into its rhizosphere plausibly to meet its requirements for nutrient uptake and stress amelioration under the different tillage and residue management practices.
Ginsenoside Rg1 defenses PC-12 cells against hydrogen peroxide-caused damage via up-regulation of miR-216a-5p
Authors: Yi Guangkun , Liu Li , Lv Chaoliang , Wei Yanchun , Yan Tingzhen 
Published: June 2019

AbstractBackgroundSpinal cord injury (SCI) is a destructive trauma accompanying with local injury, half of which cause chronic paralysis. Ginsenoside Rg1 exerts anti-apoptosis and anti-autophagy properties. Therefore, our goal was to study the protective mechanism of Rg1 in attenuating cell injury.MethodsMiR-216a-5p inhibitor was transfected into PC-12 cells, then cells were pre-treated by Rg1 and treated with 300 μM hydrogen peroxide (H2O2) for 24 h. CCK-8 and apoptosis experiments were done to test cell activity and apoptosis respectively. Expression of miR-216a-5p and cell damage relative factors was tested via qRT-PCR and western blot experiments, respectively.ResultsH2O2induced cell activity suppression, apoptosis and autophagy well at the concentration of 300 μM, leading cell injury. Rg1 could attenuate cell injury induced by H2O2at the working concentration of 200 μM that it elevated cell activity, attenuated apoptosis and autophagy and activated PI3K/AKT and AMPK signal pathways. Further, miR-216a-5p was up-regulated by Rg1. Rg1 played its role in relieving cell injury by positively regulating miR-216a-5p.ConclusionOur study demonstrated that Rg1 attenuated H2O2-caused cell injury through positively regulated miR-216a-5p.