bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospects for high gain inertial fusion energy: an introduction to the second edition
Authors: Norreys Peter A. , Ridgers Christopher , Lancaster Kate , Koepke Mark , Tynan George
Published: December 2020

Part II of this special edition contains the remaining 11 papers arising from a Hooke discussion meeting held in March 2020 devoted to exploring the current status of inertial confinement fusion research worldwide and its application to electrical power generation in the future, via the development of an international inertial fusion energy programme. It builds upon increased coordination within Europe over the past decade by researchers supported by the EUROFusion Enabling Research grants, as well as collaborations that have arisen naturally with some of America's and Asia's leading researchers, both in the universities and national laboratories. The articles are devoted to informing an update to the European roadmap for an inertial fusion energy demonstration reactor, building upon the commonalities between the magnetic and inertial fusion communities’ approaches to fusion energy. A number of studies devoted to understanding the physics barriers to ignition on current facilities are then presented. The special issue concludes with four state-of-the-art articles describing recent significant advances in fast ignition inertial fusion research.

This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 2)’.
Collisionless shock acceleration in the corona of an inertial confinement fusion pellet with possible application to ion fast ignition
Authors: Boella E. , Bingham R. , Cairns R. A. , Norreys P. , Trines R. , Scott R. , Vranic M. , Shukla N. , Silva L. O.
Published: December 2020

Two-dimensional particle-in-cell simulations are used to explore collisionless shock acceleration in the corona plasma surrounding the compressed core of an inertial confinement fusion pellet. We show that an intense laser pulse interacting with the long scale-length plasma corona is able to launch a collisionless shock around the critical density. The nonlinear wave travels up-ramp through the plasma reflecting and accelerating the background ions. Our results suggest that protons with characteristics suitable for ion fast ignition may be achieved in this way.

This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 2)’.
Fast electron transport dynamics and energy deposition in magnetized, imploded cylindrical plasma
Authors: Kawahito D. , Bailly-Grandvaux M. , Dozières M. , McGuffey C. , Forestier-Colleoni P. , Peebles J. , Honrubia J. J. , Khiar B. , Hansen S. , Tzeferacos P. , Wei M. S. , Krauland C. M. , Gourdain P. , Davies J. R. , Matsuo K. , Fujioka S. , Campbell E. M. , Santos J. J. , Batani D. , Bhutwala K. , Zhang S. , Beg F. N.
Published: December 2020

Inertial confinement fusion approaches involve the creation of high-energy-density states through compression. High gain scenarios may be enabled by the beneficial heating from fast electrons produced with an intense laser and by energy containment with a high-strength magnetic field. Here, we report experimental measurements from a configuration integrating a magnetized, imploded cylindrical plasma and intense laser-driven electrons as well as multi-stage simulations that show fast electrons transport pathways at different times during the implosion and quantify their energy deposition contribution. The experiment consisted of a CH foam cylinder, inside an external coaxial magnetic field of 5 T, that was imploded using 36 OMEGA laser beams. Two-dimensional (2D) hydrodynamic modelling predicts the CH density reaches

9.0
 

g cm

−
3

, the temperature reaches 920 eV and the external B-field is amplified at maximum compression to 580 T. At pre-determined times during the compression, the intense OMEGA EP laser irradiated one end of the cylinder to accelerate relativistic electrons into the dense imploded plasma providing additional heating. The relativistic electron beam generation was simulated using a 2D particle-in-cell (PIC) code. Finally, three-dimensional hybrid-PIC simulations calculated the electron propagation and energy deposition inside the target and revealed the roles the compressed and self-generated B-fields play in transport. During a time window before the maximum compression time, the self-generated B-field on the compression front confines the injected electrons inside the target, increasing the temperature through Joule heating. For a stronger B-field seed of 20 T, the electrons are predicted to be guided into the compressed target and provide additional collisional heating.

This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 2)’.
Whole-beam self-focusing in fusion-relevant plasma
Authors: Spiers B. T. , Hill M. P. , Brown C. , Ceurvorst L. , Ratan N. , Savin A. F. , Allan P. , Floyd E. , Fyrth J. , Hobbs L. , James S. , Luis J. , Ramsay M. , Sircombe N. , Skidmore J. , Aboushelbaya R. , Mayr M. W. , Paddock R. , Wang R. H. W. , Norreys P. A.
Published: December 2020

Fast ignition inertial confinement fusion requires the production of a low-density channel in plasma with density scale-lengths of several hundred microns. The channel assists in the propagation of an ultra-intense laser pulse used to generate fast electrons which form a hot spot on the side of pre-compressed fusion fuel. We present a systematic characterization of an expanding laser-produced plasma using optical interferometry, benchmarked against three-dimensional hydrodynamic simulations. Magnetic fields associated with channel formation are probed using proton radiography, and compared to magnetic field structures generated in full-scale particle-in-cell simulations. We present observations of long-lived, straight channels produced by the Habara–Kodama–Tanaka whole-beam self-focusing mechanism, overcoming a critical barrier on the path to realizing fast ignition.

This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 2)’.
Legionella septentrionalis sp. nov., isolated from aquatic environments in the northern PR China
Authors: Li Liang-Hui , Zhang Lei , Wu Hai-Yan , Qu Ping-Hua , Chen Jia-Chang , Zhan Xiao-Yong , Zhu Qing-Yi , Chen Cha , Hu Chao-Hui
Published: December 2020

Four strains (km711T, km714, km542 and km524), representing a novel

Legionella

species, were isolated from aquatic environments in northern PR China. Cells were Gram-stain-negative, rod-shaped, microaerobic, motile and growth depended on l-cysteine. They grew at 25‒42 °C (optimum, 35‒37 °C) and could tolerate up to 1.5 % (w/v) NaCl (optimum, 0.5 %). The major fatty acids (>5 %) of the type strain km711T were C17 : 0 anteiso, C15 : 0 anteiso, iso-C16 : 0 and C16 : 1
 ω7c and/or iso-C15 : 0 2OH. The pairwise comparison values were <96.1 % for 16S rRNA gene sequences, 23.3‒28.7 % interspecies variation for mip gene sequences, <93.6 % average nucleotide identity and <72.8 % average amino acid identity between these four strains and related type strains within the genus

Legionella

. The phylogenetic tree based on the four concatenated genes (16S rRNA, mip, rpoB and rnpB) and protein-concatamer tree based on concatenation of 21 protein markers both revealed that these four strains formed a separate phylogenetic branch cluster within the genus

Legionella

. The results of phenotypic and genotypic features suggest that these four strains represent a novel species of the genus

Legionella

, for which the name Legionella septentrionalis sp. nov. is proposed (type strain km711T=KCTC 15655T=NBRC 113219T).
Lox’d in translation: contradictions in the nomenclature surrounding common lox-site mutants and their implications in experiments
Authors: Shaw Daniel , Serrano Luis , Lluch-Senar Maria
Published: December 2020

The Cre-Lox system is a highly versatile and powerful DNA recombinase mechanism, mainly used in genetic engineering to insert or remove desired DNA sequences. It is widely utilized across multiple fields of biology, with applications ranging from plants, to mammals, to microbes. A key feature of this system is its ability to allow recombination between mutant lox sites. Two of the most commonly used mutant sites are named lox66 and lox71, which recombine to create a functionally inactive double mutant lox72 site. However, a large portion of the published literature has incorrectly annotated these mutant lox sites, which in turn can lead to difficulties in replication of methods, design of proper vectors and confusion over the proper nomenclature. Here, we demonstrate common errors in annotations, the impacts they can have on experimental viability, and a standardized naming convention. We also show an example of how this incorrect annotation can induce toxic effects in bacteria that lack optimal DNA repair systems, exemplified by

Mycoplasma pneumoniae

.
Development and Validation of an Obstetric Early Warning System model for use in low resource settings
Authors: Umar Aminu , Manu Alexander , Mathai Matthews , Ameh Charles
Published: December 2020

Background

The use of obstetric early-warning-systems (EWS) has been recommended to improve timely recognition, management and early referral of women who have or are developing a critical illness. Development of such prediction models should involve a statistical combination of predictor clinical observations into a multivariable model which should be validated. No obstetric EWS has been developed and validated for low resource settings. We report on the development and validation of a simple prediction model for obstetric morbidity and mortality in resource-limited settings.

Methods

We performed a multivariate logistic regression analysis using a retrospective case-control analysis of secondary data with clinical indices predictive of severe maternal outcome (SMO). Cases for design and validation were randomly selected (n=500) from 4360 women diagnosed with SMO in 42 Nigerian tertiary-hospitals between June 2012 and mid-August 2013. Controls were 1000 obstetric admissions without SMO diagnosis. We used clinical observations collected within 24 hours of SMO occurrence for cases, and normal births for controls. We created a combined dataset with two controls per case, split randomly into development (n=600) and validation (n=900) datasets. We assessed the model’s validity using sensitivity and specificity measures and its overall performance in predicting SMO using receiver operator characteristic (ROC) curves. We then fitted the final developmental model on the validation dataset and assessed its performance. Using the reference range proposed in the United Kingdom Confidential-Enquiry-into-Maternal-and-Child-Health 2007-report, we converted the model into a simple score-based obstetric EWS algorithm.

Results

The final developmental model comprised abnormal systolic blood pressure-(SBP>140mm Hg or <90mmHg), high diastolic blood pressure-(DBP>90mmHg), respiratory rate-(RR>40/min), temperature-(>38°C), pulse rate-(PR>120/min), caesarean-birth, and the number of previous caesarean-births. The model was 86 % (95% CI 81-90) sensitive and 92%-(95% CI 89-94) specific in predicting SMO with area under ROC of 92% (95% CI 90% – 95%). All parameters were significant in the validation model except DBP. The model maintained good discriminatory power in the validation (n=900) dataset (AUC 92, 95% CI 88-94%) and had good screening characteristics. Low urine output (300mls/24hours) and conscious level (prolonged unconsciousness-GCS<8/15) were strong predictors of SMO in the univariate analysis.

Conclusion

We developed and validated statistical models that performed well in predicting SMO using data from a low resource settings. Based on these, we proposed a simple score based obstetric EWS algorithm with RR, temperature, systolic BP, pulse rate, consciousness level, urinary output and mode of birth that has a potential for clinical use in low-resource settings.
Improved Sensitivity of Digits-in-Noise Test to High-Frequency Hearing Loss
Authors: Zadeh Lina Motlagh , Silbert Noah H. , Swanepoel De Wet , Moore David R.
Published: December 2020

Objectives

Hearing loss is most commonly observed at high frequencies. High-frequency hearing loss (HFHL) precedes and predicts hearing loss at lower frequencies. It was previously shown that an automated, self-administered digits-in-noise (DIN) test can be sensitized for detection of HFHL by low-pass filtering the speech-shaped masking noise at 1.5 kHz. This study was designed to investigate whether sensitivity of the DIN to HFHL can be enhanced further using low-pass noise filters with higher cutoff frequencies.

Design

US-English digits 0-9, homogenized for audibility, were binaurally presented in different noise maskers including one broadband and three low-pass (cut-off at 2, 4, 8 kHz) filtered speech-shaped noises. DIN-Speech reception thresholds (SRTs) were obtained from 60 normal hearing (NH), and 40 mildly hearing impaired (HI) listeners with bilateral symmetric sensorineural hearing-loss. Standard and extended high frequency audiometric pure tone averages (PTAs) were compared with the DIN-SRTs.

Results

Narrower masking noise bandwidth generally produced better (more sensitive) mean DIN-SRTs. There were strong and significant correlations between SRT and PTA in the HI group. Lower frequency, PTALF 0.5,1, 2, 4 kHz had the highest correlation and steepest slope with SRTs obtained from the 2 kHz filter. Higher frequency, PTAHF 4,8,10,12.5 kHz correlated best with SRTs obtained from 4 and 8 kHz filtered noise. The 4 kHz low-pass filter also had the highest sensitivity (92%) and equally-highest (with the 8 kHz filter) specificity (90%) for detecting an average PTAHF of 20 dB or more.

Conclusions

Of the filters used, DIN sensitivity to higher frequency hearing loss was greatest using the 4 kHz low-pass filter. These results suggest that low-pass filtered noise may be usefully substituted for broadband noise to improve earlier detection of HFHL using DIN.
PipeMaster: inferring population divergence and demographic history with approximate Bayesian computation and supervised machine-learning in R
Authors: Gehara Marcelo , Mazzochinni Guilherme G. , Burbrink Frank
Published: December 2020

Understanding population divergence involves testing diversification scenarios and estimating historical parameters, such as divergence time, population size and migration rate. There is, however, an immense space of possible highly parameterized scenarios that are difsficult or impossible to solve analytically. To overcome this problem researchers have used alternative simulation-based approaches, such as approximate Bayesian computation (ABC) and supervised machine learning (SML), to approximate posterior probabilities of hypotheses. In this study we demonstrate the utility of our newly developed R-package to simulate summary statistics to perform ABC and SML inferences. We compare the power of both ABC and SML methods and the influence of the number of loci in the accuracy of inferences; and we show three empirical examples: (i) the Muller’s termite frog genomic data from Southamerica; (ii) the cottonmouth and (iii) and the copperhead snakes sanger data from Northamerica. We found that SML is more efficient than ABC. It is generally more accurate and needs fewer simulations to perform an inference. We found support for a divergence model without migration, with a recent bottleneck for one of the populations of the southamerican frog. For the cottonmouth we found support for divergence with migration and recent expansion and for the copperhead we found support for a model of divergence with migration and recent bottleneck. Interestingly, by using an SML method it was possible to achieve high accuracy in model selection even when several models were compared in a single inference. We also found a higher accuracy when inferring parameters with SML.
Large-scale prediction of key dynamic interacting proteins in multiple cancers
Authors: Zhang Jifeng , Wang Xiao , Ji Zhicheng , Tian Weidong
Published: December 2020

Tracking cancer dynamic protein-protein interactions(PPIs) and deciphering their pathogenesis remain a challenge. Here, we presented a dynamic PPIs’ hypothesis: permanent and transient interactions might achieve dynamic switchings from normal cells to malignancy, which could cause maintenance functions to be interrupted and transient functions to be sustained. Based on the hypothesis, we first predicted more than 1,400 key cancer genes (KCG) by applying PPI-express we proposed to 18 cancer gene expression datasets. Two prominent functional characteristics, “Cell cycle-related” and “Immune-related”, were presented, suggesting that it might be a general characteristic of KCG. We then further screened out key dynamic interactions (KDI) of cancer based on KCG and transient and permanent interactions under both conditions. We found that, compared to permanent to transient KDI pairs (P2T) in the network, transient to permanent (T2P) have significantly higher edge betweenness (EB), and P2T pairs tending to locate intra-functional modules may play roles in maintaining normal biological functions, while T2P KDI pairs tending to locate inter-modules may play roles in biological signal transduction. It was consistent with our hypothesis. Also, we analyzed network characteristics of KDI pairs and their functions. Our findings of KDI may serve to understand and explain a few hallmarks of cancer.
Uncovering the ideal plant ideotype for maximising seed yield inBrassica napus
Authors: Siles Laura , Hassall Kirsty L. , Sanchis-Gritsch Cristina , Eastmond Peter J. , Kurup Smita
Published: December 2020

Seed yield is a complex trait for many crop species including oilseed rape (Brassica napus), the second most important oilseed crop worldwide. Studies have focused on the contribution of distinct factors in seed yield such as environmental cues, agronomical practices, growth conditions or specific phenotypic traits at the whole plant level, such as number of pods in a plant. However, in spite of the immense economic importance of oilseeds, none of these studies have comprehensively analysed individual traits and their combined contribution to seed yield. Here, we describe the analysis and contribution of 33 phenotypic traits within aB. napusdiversity set population and their trade-offs on seed yield not only at the whole plant level but also the less studied female reproductive traits. Our results revealed that both winter and spring oilseed rape; the two more economically important oilseed rape groups in terms of oil production; were found to share a common dominant reproductive strategy for seed yield. In this strategy the main inflorescence is the principal source of seed yield, producing a good number of ovules, a large number of long pods with a concomitantly high number of seeds per pod. We observed that winter oilseed rape opted for more reproductive strategies than spring oilseed rape, presenting more environmental flexibility to maximise seed yield. Overall, we conclude that, oilseed rape adopts a similar strategy that is key for maximal seed yield and propose an ideal ideotype highlighting crucial phenotypic traits that could be potential targets for breeding.

One sentence summary

The main florescence is the principal source of seed yield in winter and spring oilseed rape, with winter oilseed rape following several reproductive strategies to maximise seed yield.
Neural mechanisms underlying the temporal control of sequential saccade planning in the frontal eye fields
Authors: Basu Debaleena , Sendhilnathan Naveen , Murthy Aditya
Published: December 2020

Sequences of saccadic eye movements are instrumental in navigating our visual environment. While neural activity has been shown to ramp up to a threshold before single saccades, the neural underpinnings of multiple saccades is unknown. To understand the neural control of rapid saccade sequences, we recorded from the frontal eye field (FEF) of macaque monkeys while they performed a sequential saccade task. We show that concurrent planning of two saccade plans brings forth processing bottlenecks, specifically by decreasing the growth rate and increasing the threshold of saccade-related ramping activity. The rate disruption affected both saccade plans, and a computational model wherein activity related to the two saccade plans bilaterally and asymmetrically inhibited each other, predicted the behavioral and neural results observed experimentally. Borrowing from models in psychology, our results demonstrate a capacity-sharing mechanism of processing bottlenecks, wherein multiple saccade plans in a sequence, compete for the processing capacity by perturbation of the saccade-related ramping activity. Finally, we show that in contrast to movement related neurons, visual activity in FEF neurons is not affected by the presence of multiple saccade targets, indicating that for perceptually simple tasks, inhibition amongst movement-related neurons mainly instantiates capacity sharing. Taken together, we show how psychology-inspired models of capacity sharing can be mapped onto neural responses to understand the control of rapid saccade sequences.
Identification of High risk nsSNPs in Human TP53 Gene Associated with Li–Fraumeni Syndrome: An In Silico Analysis Approach
Authors: Mustafa Mujahed I. , Murshed Naseem S. , Elbasher Mazen A. , Makhawi Abdelrafie M.
Published: December 2020

Background

Li–Fraumeni syndrome (LFS) is a cancer–prone conditions caused by a germline mutation of the TP53 gene on chromosome 17p13.1. It has an autosomal dominant pattern of inheritance with high penetrance.

Purpose

The aim of this study is to identify the high-risk pathogenic nsSNPs in PT53 gene that could be involved in the pathogenesis of Li–Fraumeni syndrome.

Methods

The nsSNPs in the human PT53 gene retrieved from NCBI, were analyzed for their functional and structural consequences using various in silico tools to predict the pathogenicity of each SNP. SIFT, Polyphen, PROVEAN, SNAP2, SNPs&Go, PHD-SNP, and P-Mut were chosen to study the functional inference while I-Mutant 3.0, and MUPro tools were used to test the impact of amino acid substitutions on protein stability by calculating ΔΔG value. The effects of the mutations on 3D structure of the PT53 protein were predicted using RaptorX and visualized by UCSF Chimera.

Results

A total of 845 PT53 nsSNPs were analyzed. Out of 7 nsSNPs of PT53 three of them (T118L, C242S, and I251N) were found high-risk pathogenic.

Conclusion

In this study, out of 7 predicted high-risk pathogenic nsSNPs, three high-risk pathogenic nsSNPs of PT53 gene were identified, which could be used as diagnostic marker for this gene. The combination of sequence-based and structure-based approaches is highly effective for pointing pathogenic regions.
In silico identification of novel chemical compounds with anti-TB potential for the inhibition of InhA and EthR from Mycobacterium tuberculosis
Authors: Halder Sajal Kumar , Elma Fatiha
Published: December 2020

Tuberculosis (TB) continuously pose a major public health concern around the globe, with a mounting death toll of approximately 1.4 million in 2019. The reduced bioavailability, increased toxicity and resistance of several first-line and second-line anti-TB drugs such as isoniazid, ethionamide have necessitated the search for new medications. In this research, we have identified several novel chemical compounds with anti-TB properties using various computational tools like molecular docking analysis, drug-likeness evaluation, ADMET profiling, P450 site of metabolism prediction and molecular dynamics simulation study. This study involves fifty drug-like compounds with antibacterial activity that inhibit InhA and EthR involved in the synthesis of one of the major lipid components, mycolic acid, which is crucial for the viability ofMycobacterium tuberculosis.Among these fifty compounds, 3-[3-(4-Fluorophenyl)-1,2,4-oxadiazol-5-yl]-N-(2-methylphenyl) piperidine-1-carboxamide (C22) and 5-(4-Ethyl-phenyl)-2-(1H-tetrazol-5-ylmethyl)-2H-tetrazole (C29) were found to pass the two-step molecular docking, P450 site of metabolism prediction and pharmacokinetics filtering analysis successfully. Their binding stability for target proteins have been evaluated through RMSD, RMSF, Radius of gyration analysis from 10 ns Molecular Dynamics Simulation (MDS) run. Our identified drugs could be a capable therapeutic for Tuberculosis drug discovery, having said that more in vitro and in vivo testing is required to justify their potential as novel drug and mode of action.
Scalable inference of transcriptional kinetic parameters from MS2 time series data
Authors: Bowles Jonathan R. , Hoppe Caroline , Ashe Hilary L. , Rattray Magnus
Published: December 2020

Abstract

Motivation

The MS2-McP (MS2 coat protein) live imaging system allows for visualisation of transcription dynamics through the introduction of hairpin stem-loop sequences into a gene. A fluorescent signal at the site of nascent transcription in the nucleus quantifies mRNA production. computational modelling can be used to infer the promoter states along with the kinetic parameters governing transcription, such as promoter switching frequency and polymerase loading rate. However, modelling of the fluorescent trace presents a challenge due its persistence; the observed fluorescence at a given time point depends on both current and previous promoter states. A memory-adjusted Hidden Markov Model (mHMM) was recently introduced to allow inference of promoter activity from MS2-McP data. However, the computational time for inference scales exponentially with gene length and the mHMM is therefore not currently practical for application to many eukaryotic genes.

Results

We present a scalable implementation of the mHMM for fast inference of promoter activity and transcriptional kinetic parameters. This new method can model genes of arbitrary length through the use of a time-adaptive truncated compound state space. The truncated state space provides a good approximation to the full state space by retaining the most likely set of states at each time during the forward pass of the algorithm. Testing on MS2-MCP fluorescent data collected from earlyDrosophila melanogasterembryos indicates that the method provides accurate inference of kinetic parameters within a computationally feasible timeframe. The inferred promoter traces generated by the model can also be used to infer single-cell transcriptional parameters.

Availability

Python implementation available athttps://github.com/ManchesterBioinference/burstInfer, along with code to reproduce the examples presented here.
Bridging the gap betweenin silicoandin vivo:modeling opioid disposition in a kidney proximal tubule microphysiological system
Authors: Imaoka Tomoki , Huang Weize , Shum Sara , Hailey Dale W. , Chang Shih-Yu , Chapron Alenka , Yeung Catherine K. , Himmelfarb Jonathan , Isoherranen Nina , Kelly Edward J.
Published: December 2020

Background

Opioid overdose, dependence, and addiction are a major public health crisis. Patients with chronic kidney disease (CKD) are at high risk of opioid overdose, therefore novel methods that provide accurate prediction of kidney clearance (CLr) and systemic disposition of opioids in CKD patients can facilitate the optimization of therapeutic regimens.

Methods

We conducted prediction of kidney clearance and systemic disposition of morphine and its active metabolite morphine-6-glucuronide (M6G) in CKD patients using a vascularized human proximal tubule microphysiological system (VPT-MPS) coupled with a parent-metabolite full body physiologically-based pharmacokinetic (PBPK) model.

Results

The VPT-MPS, populated with a human umbilical vein endothelial cell (HUVEC) channel and an adjacent human primary proximal tubular epithelial cells (PTEC) channel, successfully demonstrated secretory transport of morphine and M6G from the HUVEC channel into the PTEC channel in a time-dependent manner; transporter inhibitors decreased translocation by 74.3% and 63.6%, respectively. Thein vitrodata generated by VPT-MPS were incorporated into a mechanistic kidney model and parent-metabolite full body PBPK model to predict CLrand systemic disposition of morphine and M6G. The model successfully predicted CLrwithin 1.5-fold, and the plasma concentration-time profiles of morphine and M6G in both healthy subjects and CKD patients, with absolute average fold error values <1.5.

Conclusions

A microphysiological system together with mathematical modeling successfully predicted kidney clearance and systemic disposition of opioids in CKD patients and healthy subjects.
A Universal Deep Neural Network for In-Depth Cleaning of Single-Cell RNA-Seq Data
Authors: Li Hui , Brouwer Cory R. , Luo Weijun
Published: December 2020

Single cell RNA sequencing (scRNA-Seq) has been widely used in biomedical research and generated enormous volume and diversity of data. The raw data contain multiple types of noise and technical artifacts and need thorough cleaning. The existing denoising and imputation methods largely focus on a single type of noise (i.e. dropouts) and have strong distribution assumptions which greatly limit their performance and application. We designed and developed the AutoClass model, integrating two deep neural network components, an autoencoder and a classifier, as to maximize both noise removal and signal retention. AutoClass is free of distribution assumptions, hence can effectively clean a wide range of noises and artifacts. AutoClass outperforms the state-of-art methods in multiple types of scRNA-Seq data analyses, including data recovery, differential expression analysis, clustering analysis and batch effect removal. Importantly, AutoClass is robust on key hyperparameter settings including bottleneck layer size, pre-clustering number and classifier weight. We have made AutoClass open source at:https://github.com/datapplab/AutoClass.
De novoconstruction of a transcriptome for the stink bug crop pestChinavia impicticornisduring late development
Authors: Genevcius Bruno C. , Torres Tatiana T.
Published: December 2020

Chinavia impicticornisis a Neotropical stink-bug (Hemiptera: Pentatomidae) with economic importance for different crops. Little is known about the development of the species, as well as the genetic mechanisms that may favor the establishment of populations in cultivated plants. Here we conduct the first large-scale molecular study withC. impicticornis. We generated RNA-seq data for males and females, at two immature stages, for the genitalia separately and for the rest of the body. We assembled the transcriptome and conduct a functional annotation.De novoassembled transcriptome based on whole bodies and genitalia of males and females contained around 400,000 contigs with an average length of 688 bp. After pruning duplicated sequences and conducting a functional annotation, the final annotated transcriptome comprised 39,478 transcripts of which 12,665 had GO terms assigned. These novel datasets will provide invaluable data for the discovery of molecular processes related to morphogenesis and immature biology. We hope to contribute to the growing research on stink bugevo-devoas well as the development of bio-rational solutions for pest management.
Cardiac metabolic imaging using hyperpolarized [1-13C]lactate as a substrate
Authors: Lau Angus Z , Chen Albert P , Cunningham Charles H
Published: December 2020

Hyperpolarized [1-13C]lactate is an attractive alternative to [1-13C]pyruvate as a substrate to investigate cardiac metabolism in vivo; it can be administered safely at a higher dose and can be polarized to a similar degree as pyruvate via dynamic nuclear polarization. While13C cardiac experiments using HP lactate have been performed in small animal models, it has not been demonstrated in large animal models or humans. Utilizing the same hardware and data acquisition methods used in the first human HP13C cardiac study, 13C metabolic images were acquired following injections of HP [1-13C]lactate in porcine hearts. Data were also acquired using HP [1-13C]pyruvate for comparison. The13C bicarbonate signal was localized to the myocardium and had a similar appearance with both substrates for all animals. No13C pyruvate signal was detected in the experiments following injection of hyperpolarized13C lactate. The SNR of injected lactate was 88 +/-14% of the SNR of injected pyruvate, and the SNR of bicarbonate in the experiments using lactate as the substrate was 52+/-19% of the SNR in the experiments using pyruvate as the substrate. The lower SNR was likely due to the shorter T1 of [1-13C]lactate as compared to [1-13C]pyruvate and the additional enzyme-catalyzed metabolic conversion step before the 13C nuclei from [1-13C]lactate were detected as13C bicarbonate. While challenges remain, the potential of HP lactate as a substrate for clinical metabolic imaging of human heart was demonstrated.
Assessing bird collisions in the United Kingdom: Modelling frequency of bird-strike from road and rail mortality using a Bayesian hierarchical approach
Authors: Freire Silvia , Read Lee , Lewis Todd R.
Published: December 2020

Roads are an important way to transport people and goods, but they sometimes have negative impacts on wildlife. One of the leading causes of mortality for several species is identified as road strikes, and the most significant remains bird-vehicle collisions. This study aimed to investigate what species of birds are most affected, and what other factors impact in their susceptibility in road collisions, such as age, sex, season, and type of transports. A total of N=5413 records, and 140 bird species were documented by BTO ringers. For analysis four Bayesian Hierarchical Models were used, with random effects results showing that Barn owls were most affected by collisions. Road mortality presents the highest cause of mortality among species when contrasted with rail mortality. Age and sexual bias was detected across all species, however juveniles and males did appear to be prominent in relation to other age classes. Winter and early spring were the months with most reported casualties and 2016 had lower abundance of mortality across the 10-year period. 75% of birds were found within a week, which may indicate some bias interference from scavenging animals, as true figures could be up to 16 times more. This study discusses some mitigation measures found in current research, that could dramatically reduce numbers of birds affected each year by road mortality.
Harnessing Colon Chip technology to identify commensal bacteria that promote host tolerance to infection
Authors: Gazzaniga Francesca S. , Camacho Diogo M. , Wu Meng , Palazzo Matheus , Dinis Alexandre , Grafton Francis N. , Cartwright Mark J. , Super Michael , Kasper Dennis L. , Ingber Donald E.
Published: December 2020

Commensal bacteria within the gut microbiome contribute to development of host tolerance to infection, however, identifying specific microbes responsible for this response is difficult. Here we describe methods for developing microfluidic organ-on-a-chip models of small and large intestine lined with epithelial cells isolated from duodenal, jejunal, ileal, or colon organoids derived from wild type or transgenic mice. To focus on host-microbiome interactions, we carried out studies with the mouse Colon Chip and demonstrated that it can support co-culture with living gut microbiome and enable assessment of effects on epithelial adhesion, tight junctions, barrier function, mucus production, and cytokine release. Moreover, infection of the Colon Chips with the pathogenic bacterium,Salmonella typhimurium, resulted in epithelial detachment, decreased tight junction staining, and increased release of cytokines (CXCL1, CXCL2, and CCL20) that closely mimicked changes previously seen in mice. Symbiosis between microbiome bacteria and the intestinal epithelium was also recapitulated by populating Colon Chips with complex living mouse or human microbiome. By taking advantage of differences in the composition between complex microbiome samples cultured on each chip using 16s sequencing, we were able to identifyEnterococcus faeciumas a positive contributor to host tolerance, confirming past findings obtained in mouse experiments. Thus, mouse Intestine Chips may represent new experimentalin vitroplatforms for identifying particular bacterial strains that modulate host response to pathogens, as well as for investigating the cellular and molecular basis of host-microbe interactions.
Massively parallel sequencing of 165 ancestry-informative SNPs and forensic biogeographical ancestry inference in three southern Chinese Sinitic/Tai-Kadai populations
Authors: He Guanglin , Liu Jing , Wang Mengge , Zou Xing , Ming Tianyue , Zhu Sumin , Yeh Hui-Yuan , Wang Chuanchao , Wang Zheng , Hou Yiping
Published: December 2020

Ancestry informative markers (AIMs), which are distributed throughout the human genome, harbor significant allele frequency differences among diverse ethnic groups. The use of sets of AIMs to reconstruct population history and genetic relationships is attracting interest in the forensic community, because biogeographic ancestry information for a casework sample can potentially be predicted and used to guide the investigative process. However, subpopulation ancestry inference within East Asia remains in its infancy due to a lack of population reference data collection and incomplete validation work on newly developed or commercial AIM sets. In the present study, 316 Chinese persons, including 85 Sinitic-speaking Haikou Han, 120 Qiongzhong Hlai and 111 Daozhen Gelao individuals belonging to Tai-Kadai-speaking populations, were analyzed using the Precision ID Ancestry Panel (165 AISNPs). Combined with our previous 165-AISNP data (375 individuals from 6 populations), the 1000 Genomes Project and forensic literature, comprehensive population genetic comparisons and ancestry inference were further performed via ADMIXTURE, TreeMix, PCA,f-statistics and N-J tree. Although several nonpolymorphic loci were identified in the three southern Chinese populations, the forensic parameters of this ancestry inference panel were better than those for the 23 STR-based Huaxia Platinum System, which is suitable for use as a robust tool in forensic individual identification and parentage testing. The results based on the ancestry assignment and admixture proportion evaluation revealed that this panel could be used successfully to assign individuals at a continental scale but also possessed obvious limitations in discriminatory power in intercontinental individuals, especially for European-Asian admixed Uyghurs or in populations lacking reference databases. Population genetic analyses further revealed five continental population clusters and three East Asian-focused population subgroups, which is consistent with linguistic affiliations. Ancestry composition and multiple phylogenetic analysis further demonstrated that the geographically isolated Qiongzhong Hlai harbored a close phylogenetic relationship with Austronesian speakers and possessed a homogenous Tai-Kadai-dominant ancestry, which could be used as the ancestral source proxy in population history reconstruction of Tai-Kadai-speaking populations and as one of the representatives for forensic database establishment. In summary, more population-specific AIM sets focused on East Asian subpopulations, comprehensive algorithms and high-coverage population reference data should be developed and validated in the next step.
Genomics of altitude-associated wing shape in two tropical butterflies
Authors: Montejo-Kovacevich Gabriela , Salazar Patricio A. , Smith Sophie H. , Gavilanes Kimberly , Bacquet Caroline N. , Chan Yingguang Frank , Jiggins Chris D. , Meier Joana I. , Nadeau Nicola J.
Published: December 2020

Understanding how organisms adapt to their local environment is central to evolution. With new whole-genome sequencing technologies and the explosion of data, deciphering the genomic basis of complex traits that are ecologically relevant is becoming increasingly feasible. Here we study the genomic basis of wing shape in two Neotropical butterflies that inhabit large geographical ranges.Heliconiusbutterflies at high elevations have been shown to generally have rounder wings than those in the lowlands. We reared over 1100 butterflies from 71 broods ofH. eratoandH. melpomenein common-garden conditions and show that wing aspect ratio, i.e. elongatedness, is highly heritable in both species and elevation-associated wing shape differences are maintained. Genome-wide associations with a published dataset of 666 whole genomes from across a hybrid zone, uncovered a highly polygenic basis to wing shape variation in the wild. We identify several genes that have roles in wing morphogenesis or wing shape variation inDrosophilaflies, making them promising candidates for future studies. There was little evidence for molecular parallelism in the two species, with only one shared candidate gene, nor for a role of the four known colour pattern loci, except foroptixinH. erato. Thus, we present the first insights into the heritability and genomic basis of within-species wing shape in twoHeliconiusspecies, adding to a growing body of evidence that polygenic adaptation may underlie many ecologically relevant traits.
Functional maps of the primate cortex revealed by through-skull wide-field optical imaging
Authors: Song Xindong , Guo Yueqi , Li Hongbo , Chen Chenggang , Schmidt Zachary , Wang Xiaoqin
Published: December 2020

The primate cerebral cortex is organized into specialized areas representing different functional modalities (e.g., vision, audition, touch) and their associations along a continuous surface. The functional maps of these areas, however, are often investigated in a single modality at a time. Here, we developed and applied to awake primates a polarization-enhanced wide-field optical imaging method for measuring cortical hemodynamics through the intact skull. Adjacent somatosensory, auditory, and visual cortices were noninvasively localized and rapidly parcellated in awake marmosets (Callithrix jacchus), a primate model featuring a smooth cortex. Detailed somatotopy, tonotopy, and retinotopy were also mapped out on an individual-subject basis, with a new pure-tone-responsive tonotopic gradient discovered outside the auditory core. Moreover, the motion-sensitive extent surrounding the primate-specific MT/V5 and the location of a face-sensitive patch were both revealed with respect to retinotopy. This approach provides a powerful tool for mapping the functional landscape across modalities in a single non-human primate subject, and thus opens new opportunities for probing how primate cortical system is organized to enable real-world behaviors.
Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior
Authors: Yasumoto Yuki , Stoiljkovic Milan , Kim Jung Dae , Sestan-Pesa Matija , Gao Xiao-Bing , Diano Sabrina , Horvath Tamas L.
Published: December 2020

Microglia have been implicated in synapse remodeling by phagocytosis of synaptic elements in the adult brain. However, the underlying mechanism of such process is ill-defined. By examining microglia-neuronal interaction in the ventral hippocampus, we found a significant reduction in spine synapse number during the light phase of the light/dark cycle accompanied by increased microglial phagocytosis. This was followed by a transient rise in microglial production of reactive oxygen species (ROS) and uncoupling protein 2 (Ucp2) expression, which is a regulator of mitochondrial ROS generation. Conditional ablation of microglialUcp2hindered phasic elimination of spine synapses, increased accumulations of ROS and lysosome-lipid droplet complexes leading to hippocampal circuitry disruption assessed by electrophysiology, and, altered anxiety-like behavior. These observations unmasked a novel and chronotypical interaction between microglia and neurons involved in control of brain functions.
Marine Bacteria Associated with the Green SeaweedUlvasp. for the Production of Polyhydroxyalkanoates
Authors: Gnaim Rima , Polikovsky Mark , Unis Razan , Sheviryov Julia , Gozin Michael , Golberg Alexander
Published: December 2020

The biosynthesis of polyhydroxyalkanoate (PHA) biopolymers from certain marine microbes, associated with green macroalgaeUlvasp., has attracted significant attention. TheUlvasp. is abundant biomass in numerous locations around the world and could be easily cultivated by marine farming. The variety of sugars found inUlvasp. homogenate could be used as a carbon source for microbial growth and PHA production. In this work, we isolated and explored a series of bacterial strains that function as potential producers of P(3HB), utilizing a range of common sugars found inUlvasp. Analysis of 16S rDNA gene-sequence revealed that the PHA-producing bacteria were phylogenetically related to species of the genusCobetia, Bacillus, Pseudoaltermonas, andSulfito-bacter. The highest-yield of P(3HB) was observed in the case of newCobetiastrain,C. amphilecti, with up to 61% (w/w) in the presence of mannitol and 12% (w/w) onUlvasp. acid hydrolysate as a substrate.
Whole Genome Sequencing for Revealing the Point Mutations of SARS-CoV-2 Genome in Bangladeshi Isolates and their Structural Effects on Viral Proteins
Authors: Hossain Mohammad Uzzal , Ahammad Ishtiaque , Hossain Emon Md. Tabassum , Bhattacharjee Arittra , Chowdhury Zeshan Mahmud , Mosaib Md. Golam , Das Keshob Chandra , Keya Chaman Ara , Salimullah Md.
Published: December 2020

Coronavirus disease-19 (COVID-19) is the recent global pandemic caused by the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The virus has already killed more than one million people worldwide and billions are at risk of getting infected. As of now, there is neither any drug nor any vaccine in sight with conclusive scientific evidence that it can cure or provide protection against the illness. Since novel coronavirus is a new virus, mining its genome sequence is of crucial importance for drug/vaccine(s) development. Whole genome sequencing is a helpful tool in identifying genetic changes that occur in a virus when it spreads through the population. In this study, we performed complete genome sequencing of SARS-CoV-2 to unveil the genomic variation and indel, if present. We discovered thirteen (13) mutations in Orf1ab, S and N gene where seven (7) of them turned out to be novel mutations from our sequenced isolate. Besides, we found one (1) insertion and seven (7) deletions from the indel analysis among the 323 Bangladeshi isolates. However, the indel did not show any effect on proteins. Our energy minimization analysis showed both stabilizing and destabilizing impact on viral proteins depending on the mutation. Interestingly, all the variants were located in the binding site of the proteins. Furthermore, drug binding analysis revealed marked difference in interacting residues in mutants when compared to the wild type. Our analysis also suggested that eleven (11) mutations could exert damaging effects on their corresponding protein structures. The analysis of SARS-CoV-2 genetic variation and their impacts presented in this study might be helpful in gaining a better understanding of the pathogenesis of this deadly virus.