bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual-Energy Low-keV or Single-Energy Low-kV CT for Endoleak Detection?
Authors: Skawran Stephan , Angst Florian , Blüthgen Christian , Eberhard Matthias , Kälin Pascal , Kobe Adrian , Nagy Daniel , Szucs-Farkas Zsolt , Alkadhi Hatem , Euler André
Published: September 2019

Objectives

The aim of this study was to compare image quality, conspicuity, and endoleak detection between single-energy low-kV images (SEIs) and dual-energy low-keV virtual monoenergetic images (VMIs+) in computed tomography angiography of the aorta after endovascular repair.

Materials and Methods

An abdominal aortic aneurysm phantom simulating 36 endoleaks (2 densities; diameters: 2, 4, and 6 mm) in a medium- and large-sized patient was used. Each size was scanned using single-energy at 80 kVp (A) and 100 kVp (B), and dual-energy at 80/Sn150kVp for the medium (C) and 90/Sn150kVp for the large size (D). VMIs+ at 40 keV and 50 keV were reconstructed from protocols C and D. Radiation dose was 3 mGy for the medium and 6 mGy for the large size. Objective image quality and normalized noise power spectrum were determined. Subjective image quality, conspicuity, and sensitivity for endoleaks were independently assessed by 6 radiologists. Sensitivity was compared using Marascuilo procedure and Fisher exact test. Conspicuities were compared using Wilcoxon-matched pairs test, analysis of variance, and Tukey test.

Results

The contrast-to-noise-ratio of the aorta was significantly higher for VMI+ compared with SEI (P< 0.001). Noise power spectrum showed a higher noise magnitude and coarser texture in VMI+. Subjective image quality and overall conspicuity was lower for VMI+ compared with SEI (P< 0.05). Sensitivity for endoleaks was overall higher in the medium phantom for SEI (60.9% for A, 62.2% for B) compared with VMI+ (54.2% for C, 49.3% for D) with significant differences between protocols B and D (P< 0.05). In the large phantom, there was no significant difference in sensitivity among protocols (P= 0.79), with highest rates for protocols B (31.4%) and C (31.7%).

Conclusions

Our study indicates that low-keV VMI+ results in improved contrast-to-noise-ratio of the aorta, whereas noise properties, subjective image quality, conspicuity, and sensitivity for endoleaks were overall superior for SEI.
Bicanalicular Lacerations: Clinical Characteristics and Surgical Outcomes With a New Bicanalicular Silicone Stent
Authors: Han Shaolei , Wang Tingting , Jia Jinchen , Sun Suhuan , Fan Yiming
Published: September 2019

Background:

Bicanalicular lacerations are relatively rare and more of a surgical challenge in clinical practice. The purpose of this study is to evaluate the clinical characteristics and surgical outcomes of bicanalicular lacerations with a new bicanalicular silicone stent at a tertiary eye care center.

Methods:

All patients who underwent bicanalicular lacerations repair from January 2013 and December 2018 were retrospectively reviewed. Data collected for each patient included patient demographics, affected sides, cause of injuries, the timing of management, associated ocular injuries, the timing of stent removal, duration of follow-up and the outcomes of the surgical repair with a new bicanalicular silicone stent.

Results:

Thirty-six patients with bicanalicular lacerations met the inclusion criteria and were enrolled in the study. The mean age of the patients was 43.8 years old (range: 2–73years). Of the 36 patients, 33 (91.7%) were males and 3 (8.3%) were females. The right eye was injured in 17 patients (47.2%). All patients underwent surgical intervention within 24 hours. The most common cause of bicanalicular lacerations was electric bicycles accidents (7 patients, 19.4%), and followed by motor vehicle accidents (6 patients, 16.7%), blunt objects (6 patients, 16.7%), fights (6 patients, 16.7%), falls (3 patients, 12%), dog bites (2 patients, 5.6%), hook injuries (2 patients, 5.6%), broken glass (2 patients, 5.6%), and sharp objects (2 patients, 5.6%). The most common associated ocular injuries were orbital fracture (61.1%), followed by lid lacerations and open globe injuries. The functional success rate was 86.1%. The average interval between the surgery and the stent removal was 13.8 weeks (range: 8–20 weeks). All the stents were removed successfully without any difficulty in the outpatient department. The follow-up after stent removal ranged from 2 to 12 months (mean: 5.1months).

Conclusions:

Bicanalicular lacerations involvement occured in 6.8% of all canalicular lacerations. The most common cause of bicanalicular lacerations was electric bicycles accidents and the most common associated ocular injuries was orbital fracture in North China. The new bicanalicular silicone stent achieved good functional success (86.1%) in the management of bicanalicular lacerations.
A nonlinear relationship between prediction errors and learning rates in human reinforcement-learning
Authors: Ikwunne Boluwatife , Parham Jolie , Pulcu Erdem
Published: September 2019

Reinforcement-learning (RL) models have been pivotal to our understanding of how agents perform learning-based adaptions in dynamically changing environments. However, the exact nature of the relationship (e.g. linear, logarithmic etc.) between key components of RL models such as prediction errors (PEs; the difference between the agent’s expectation and the actual outcome) and learning rates (LRs; a coefficient used by agents to update their beliefs about the environment) has not been studied in detail. Here, across (i) simulations, (ii) reanalyses of readily available datasets and (iii) a novel experiment, we demonstrate that the relationship between PEs and LRs is (i) nonlinear over the PE/LR space, and (ii) it can be better accounted for by an exponential-logarithmic function that can transform the magnitude of PEs instantaneously to LRs. In line with the temporal predictions of this model, we show that physiological correlates of LRs accumulate while learners observe the outcome of their choices and update their beliefs about the environment.
High-resolution melt curve analysis for rapid detection of rifampicin resistance inmycobacterium tuberculosis: A single-center study in Iran
Authors: Arefzadeh Samaneh , Nasiri Mohammad Javad , Azimi Taher , Nikpor Zahra , Dabiri Hossein , Doustdar Farahnoosh , Goudarzi Hossein , Alahyar Mohammad
Published: September 2019

Introduction

Tuberculosis (TB) remains a leading cause of death worldwide, especially in developing countries. Early detection of resistance is extremely important to reduce the risk of death. This study was aimed to compare the diagnostic accuracy of high resolution melting (HRM) analysis in comparison with Xpert MTB/RIF as well as conventional drug susceptibility testing (DST) for the detection of rifampicin (RIF) resistance inMycobacterium tuberculosisin Iran.

Materials and methods

A comparative cross-sectional study was carried out from April 2017 to September 2018. A total of 80 culture-positive clinical samples selected during the study period were analyzed for detection of RIF-resistant TB by conventional DST, Xpert MTB/RIF, and sequencing. Sensitivity and specificity of the HRM calculated according to DST as our gold standard test in this study.

Results

The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HRM assay were found to be 100%, 89.33%, 38.46%, and 100% respectively.

Conclusions

The analysis has demonstrated that the diagnostic accuracy of HRM tests is insufficient to replace Xpert MTB/RIF and conventional DST. HRM test may be used in combination with culture due to the advantage of the time to result. Further work to improve molecular tests would benefit from standardized reference standards and the methodology.
Absence of a faster-X effect in beetles (Tribolium, Coleoptera)
Authors: Whittle Carrie A. , Kulkarni Arpita , Extavour Cassandra G.
Published: September 2019

Background

The faster-X effect, namely the rapid evolution of protein-coding genes on the X-chromosome, has been reported in numerous metazoans. However, the prevalence of this phenomenon across metazoans and its potential causes remain largely unresolved. Analysis of sex-biased genes may elucidate its possible mechanisms: a more pronounced faster-X effect in male-biased genes than in female-biased or unbiased genes, suggests fixation of recessive beneficial mutations rather than genetic drift. Further, theory predicts that the faster-X effect should be promoted by X-chromosome dosage compensation, but this topic remains rarely empirically examined.

Results

Here, we asked whether we could detect a faster-X effect in genes of the beetleTribolium castaneum(andT. freemaniorthologs), which has X/Y sex-determination and heterogametic males. Our comparison of protein sequence divergence (dN/dS) on the X-chromosome versus autosomes indicated the complete absence of a faster-X effect. Further, analyses of sex-biased gene expression revealed that the X-chromosome was strongly enriched for ovary-biased genes, which evolved under exceptionally high constraint. An evaluation of male X-chromosome dosage compensation in the gonads and in non-gonadal somatic tissues showed an extreme lack of compensation in the testis. This under-expression of the X chromosome in males may limit the phenotypic effect, and therefore likelihood of fixation, of recessive beneficial X-linked mutations in genes transcribed in male gonads.

Conclusions

We show that these beetles display a rare unequivocal example of the absence of a faster-X effect in a metazoan. We propose two potential causes for this, namely high constraint on X-linked ovary-biased genes, and an extreme lack of dosage compensation of genes transcribed in the testis.
An evaluation of Nephrology Literature for Transparency and Reproducibility Indicators: Cross-sectional Review
Authors: Fladie Ian A. , Adewumi Tomi , Vo Nam , Tritz Daniel , Vassar Matt
Published: September 2019

Background

Reproducibility is critical to diagnostic accuracy and treatment implementation. Concurrent with clinical reproducibility, research reproducibility establishes whether the use of identical study materials and methodologies in replication efforts permit researchers to arrive at similar results and conclusions. In this study, we address this gap by evaluating nephrology literature for common indicators of transparent and reproducible research.

Methods

We searched the National Library of Medicine catalog to identify 36 MEDLINE-indexed, English language nephrology journals. We randomly sampled 300 publications published between January 1, 2014, and December 31, 2018. In a duplicated and blinded fashion, two investigators screened and extracted data from the 300 publications.

Results

Our search yielded 28,835 publications, of which we randomly sampled 300 publications. Of the 300 publications, 152 (50.67%) were publicly available whereas 143 (47.67%) were restricted through paywall and 5 (1.67%) were inaccessible. Of the remaining 295 publications, 123 were excluded because they lack empirical data necessary for reproducibility. Of the 172 publications with empirical data, 43 (25%) reported data availability statements, 4 (2.33%) analysis scripts, 4 (2.33%) links to a protocol, and 10 (5.81%) were pre-registered.

Conclusion

Our study found that reproducible and transparent research practices are infrequently employed by the nephrology research community. Greater efforts should be made by both funders and journals, two entities that have the greatest ability to influence change. In doing so, an open science culture may eventually become the norm rather than the exception.
Mutation of theALBOSTRIANSOhnologous GeneHvCMF3Impairs Chloroplast Development and Thylakoid Architecture in Barley due to Reduced Plastid Translation
Authors: Li Mingjiu , Hensel Goetz , Melzer Michael , Junker Astrid , Tschiersch Henning , Arend Daniel , Kumlehn Jochen , Börner Thomas , Stein Nils
Published: September 2019

Gene pairs resulting from whole genome duplication (WGD), so-called ohnologous genes, are retained only if at least one gene of the pair undergoes neo- or subfunctionalization. Sequence-based phylogenetic analyses of the ohnologous genesALBOSTRIANS(HvAST/HvCMF7) andALBOSTRIANS-LIKE(HvASL/HvCMF3) of barley (Hordeum vulgare) revealed that they belong to a newly identified subfamily of genes encoding CCT domain proteins with putative N-terminal chloroplast transit peptides. Recently, we showed that HvCMF7 is needed for chloroplast ribosome biogenesis. Here we demonstrate that mutations inHvCMF3lead to seedlings delayed in development. They exhibit axanthaphenotype and successively develop pale green leaves. Compared to the wild type, plastids of the mutant seedlings show decreased PSII efficiency and lower amounts of ribosomal RNAs; they contain less thylakoids and grana with a higher number of more loosely stacked thylakoid membranes. Site-directed mutagenesis ofHvCMF3identified a previously unknown functional region, which is highly conserved within this subfamily of CCT domain containing proteins. HvCMF3:GFP fusion constructs localized to plastids.Hvcmf3Hvcmf7double mutants indicated epistatic activity ofHvCMF7overHvCMF3.The chloroplast ribosome deficiency is discussed as the primary defect of theHvcmf3mutants. Our data suggests that HvCMF3 and HvCMF7 have similar but not identical functions.

One-sentence summary

Phylogenetic and mutant analyses of the barley protein HvCMF3 (ALBOSTRIANS-LIKE) identified, in higher plants, a subfamily of CCT domain proteins with essential function in chloroplast development.
Antidepressant drugs act by directly binding to TRKB neurotrophin receptors
Authors: Casarotto Plinio C , Girych Mykhailo , Fred Senem M , Kovaleva Vera , Moliner Rafael , Enkavi Giray , Biojone Caroline , Cannarozzo Cecilia , Sahu Madhusmita Pryiadrashini , Kaurinkoski Katja , Brunello Cecilia A , Steinzeig Anna , Winkel Frederike , Patil Sudarshan , Vestring Stefan , Serchov Tsvetan , Diniz Cassiano RAF , Laukkanen Liina , Cardon Iseline , Antila Hanna , Rog Tomasz , Piepponen Timo Petteri , Bramham Clive R , Normann Claus , Lauri Sari E , Saarma Mart , Vattulainen Ilpo , Castrén Eero
Published: September 2019

It is unclear how binding of antidepressant drugs to their targets gives rise to the clinical antidepressant effect. We discovered that the transmembrane domain of TRKB, the brain-derived neurotrophic factor (BDNF) receptor that promotes neuronal plasticity and antidepressant responses, has a cholesterol-sensing function that mediates synaptic effects of cholesterol. We then found that both typical and fast-acting antidepressants directly bind to TRKB, thereby facilitating synaptic localization of TRKB and its activation by BDNF. Extensive computational approaches including atomistic molecular dynamics simulations revealed a binding site at the transmembrane region of TRKB dimers. Mutation of the TRKB antidepressant-binding motif impaired cellular, behavioral and plasticity-promoting responses to antidepressants in vitro and in vivo. We suggest that binding to TRKB and the allosteric facilitation of BDNF signaling is the common mechanism for antidepressant action, which proposes a framework for how molecular effects of antidepressants are translated into clinical mood recovery.
Exploratory movement analysis and report building with R package stmove
Authors: Seidel Dana P. , Dougherty Eric R. , Getz Wayne M.
Published: September 2019

Background

As GPS tags and data loggers have become lighter, cheaper, and longer-lasting, there has been a growing influx of data on animal movement. Simultaneously, methods of analyses and software to apply such methods to movement data have expanded dramatically. Even so, for many interdisciplinary researchers and managers without familiarity with the field of movement ecology and the open-source tools that have been developed, the analysis of movement data has remained an overwhelming challenge.

Description

Here we present stmove, an R package designed to take individual relocation data and generate a visually rich report containing a set of preliminary results that ecologists and managers can use to guide further exploration of their data. Not only does this package make report building and exploratory data analysis (EDA) simple for users who may not be familiar with the extent of available analytical tools, but it sets forth a framework of best practice analyses, which offers a common starting point for the interpretation of terrestrial movement data.

Results

Using data from African elephants (Loxodonta africana) collected in southern Africa, we demonstrate stmove’s report building function through the main analyses included: path visualization, primary statistic calculation, summary in space and time, and space-use construction.

Conclusions

The stmove package provides consistency and increased accessibility to managers and researchers who are interested in movement analysis but who may be unfamiliar with the full scope of movement packages and analytical tools. If widely adopted, the package will promote comparability of results across movement ecology studies.
Multidimensional and Multiresolution Ensemble Networks for Brain Tumor Segmentation
Authors: Murugesan Gowtham Krishnan , Nalawade Sahil , Ganesh Chandan , Wagner Ben , Yu Fang F. , Fei Baowei , Madhuranthakam Ananth J. , Maldjian Joseph A.
Published: September 2019

In this work, we developed multiple 2D and 3D segmentation models with multiresolution input to segment brain tumor components, and then ensembled them to obtain robust segmentation maps. This reduced overfitting and resulted in a more generalized model. Multiparametric MR images of 335 subjects from BRATS 2019 challenge were used for training the models. Further, we tested a classical machine learning algorithm (xgboost) with features extracted from the segmentation maps to classify subject survival range. Preliminary results on the BRATS 2019 validation dataset demonstrasted this method can achieve excellent performance with DICE scores of 0.898, 0.784, 0.779 for whole tumor, tumor core and enhancing tumor respectively and accuracy 34.5 % for survuval prediction.
Design principles of a minimal auxin response system
Authors: Kato Hirotaka , Mutte Sumanth K. , Suzuki Hidemasa , Crespo Isidro , Das Shubhajit , Radoeva Tatyana , Fontana Mattia , Yoshitake Yoshihiro , Hainiwa Emi , van den Berg Willy , Lindhoud Simon , Hohlbein Johannes , Borst Jan Willem , Boer D. Roeland , Nishihama Ryuichi , Kohchi Takayuki , Weijers Dolf
Published: September 2019

Auxin controls numerous growth processes in land plants through a gene expression system that modulates ARF transcription factor activity1–3. Gene duplications in families encoding auxin response components have generated tremendous complexity in most land plants, and neofunctionalization enabled various unique response outputs during development2–4. However, it is unclear what fundamental biochemical principles underlie this complex response system. By studying the minimal system in Marchantia polymorpha, we derive an intuitive and simple model where a single auxin-dependent A-ARF activates gene expression. It is antagonized by an auxin-independent B-ARF that represses common target genes. Expression patterns of both ARF proteins define developmental zones where auxin response is permitted, quantitatively tuned, or prevented. This fundamental design likely represents the ancestral system, and formed the basis for inflated, complex systems.
PK-DB: PharmacoKinetics DataBase for Individualized and Stratified Computational Modeling
Authors: Grzegorzewski Jan , Brandhorst Janosch , Eleftheriadou Dimitra , Green Kathleen , König Matthias
Published: September 2019

A multitude of pharmacokinetics studies have been published. However, due to the lack of an open database, pharmacokinetics data, as well as the corresponding meta-information, have been difficult to access. We present PK-DB (https://pk-db.com), an open database for pharmacokinetics information from clinical trials including pre-clinical research. PK-DB provides curated information on (i) characteristics of studied patient cohorts and subjects (e.g. age, bodyweight, smoking status); (ii) applied interventions (e.g. dosing, substance, route of application); (iii) measured pharmacokinetic time-courses; (iv) pharmacokinetic parameters (e.g. clearance, half-life, area under the curve). Key features are the representation of experimental errors, the normalization of measurement units, annotation of information to biological ontologies, calculation of pharmacokinetic parameters from concentration-time profiles, a workflow for collaborative data curation, strong validation rules on the data, computational access via a REST API as well as human access via a web interface. PK-DB enables meta-analysis based on data from multiple studies and data integration with computational models. A special focus lies on meta-data relevant for individualized and stratified computational modeling with methods like physiologically based pharmacokinetic (PBPK), pharmacokinetic/pharmacodynamic (PK/DB), or population pharmacokinetic (pop PK) modeling.
The gammaherpesvirus 68 viral cyclin facilitates reactivation by promoting latent gene expression
Authors: Niemeyer Brian F , Gibson Joy E , Berger Jennifer N , Oko Lauren M , Medina Eva , Clambey Eric T , van Dyk Linda F
Published: September 2019

Gammaherpesviruses establish life-long infections within their host and have been shown to be the causative agents of devastating malignancies. Chronic infection within the host is mediated through cycles of transcriptionally quiescent stages of latency with periods of reactivation into more active lytic and productive infection. The mechanisms that regulate reactivation from latency remain poorly understood. Previously, we defined a critical role for the viral cyclin in promoting reactivation from latency. Disruption of the viral cyclin had no impact on the frequency of cells containing viral genome during latency, yet it remains unclear whether the viral cyclin influences latently infected cells in a qualitative manner. To define the impact of the viral cyclin on latent gene expression, we utilized a viral cyclin deficient variant expressing a LANA-beta-lactamase fusion protein (LANA::βla), to enumerate both the cellular distribution and frequency of latent gene expression. Disruption of the viral cyclin did not affect the cellular distribution of latently infected cells, but did result in a significant decrease in the frequency of cells that expressed LANA::βla across multiple tissues and in both immunocompetent and immunodeficient hosts. Strikingly, whereas the cyclin-deficient virus had a reactivation defect in bulk culture, sort purified cyclin-deficient LANA::βla expressing cells were fully capable of reactivation. These data emphasize that the γHV68 latent reservoir is comprised of at least two distinct stages of infection characterized by differential latent gene expression, and that a primary function of the viral cyclin is to promote latent gene expression within infected cells in vivo.

AUTHOR SUMMARY

Gammaherpesviruses are ubiquitous viruses with oncogenic potential that establish latency for the life of the host. These viruses can emerge from latency through reactivation, a process that is controlled by the immune system. Control of viral latency and reactivation is thought to be critical to prevent γHV-associated disease. This study focuses on a virally-encoded cyclin that is required for reactivation from latency. By characterizing how the viral cyclin influences latent infection in pure cell populations, we find that the viral cyclin has a vital role in promoting viral gene expression during latency. This work provides new insight into the function of a virally encoded cyclin in promoting reactivation from latency.
A kinetic operational model of agonism incorporating receptor desensitization for G-protein-coupled receptors
Authors: Hoare Sam R.J. , Hall David A. , Bridge Lloyd J.
Published: September 2019

Pharmacological responses are modulated over time by regulation of signaling mechanisms. The canonical short-term regulation mechanisms are receptor desensitization and degradation of the response. Here for the first time a pharmacological model for measuring drug parameters is developed that incorporates short-term mechanisms of regulation of signaling. The model is formulated in a manner that enables measurement of drug parameters using familiar curve fitting methods. The efficacy parameter iskτ, which is simply the initial rate of signaling before it becomes limited by regulation mechanisms. The regulation parameters are rate constants,kDESfor receptor desensitization andkDfor response degradation. Efficacy and regulation are separate parameters, meaning these properties can be optimized independently of one another in drug discovery. The parameters can be applied to translate in vitro findings to in vivo efficacy in terms of the magnitude and duration of drug effect. When the time course data conform to certain shapes, for example the association exponential curve, a mechanism-agnostic approach can be applied to estimate agonist efficacy, without the need to know the underlying regulatory mechanisms. The model was verified by comparison with historical data and by fitting these data to estimate the model parameters. This new model for quantifying drug activity can be broadly applied to the short-term cell signaling assays used routinely in drug discovery and to aid their translation to in vivo efficacy, facilitating the development of new therapeutics.

Highlights

Regulation of signaling impacts measurement of drug effect

Receptor desensitization is incorporated here into a kinetic model of signaling

Drug effect and signaling regulation can now be measured independently

The analysis framework is designed for signaling assays used in drug discovery

These new analysis capabilities will aid development of new therapeutics
In your phase: Neural phase synchronisation underlies visual imagery of faces
Authors: Canales-Johnson Andrés , Lanfranco Renzo C. , Morales Juan Pablo , Martínez-Pernía David , Valdés Joaquín , Ezquerro-Nassar Alejandro , Rivera-Rei Álvaro , Ibanez Agustín , Chennu Srivas , Bekinschtein Tristan A. , Huepe David , Noreika Valdas
Published: September 2019

Mental imagery is the process through which we retrieve and recombine information from our memory to elicit the subjective impression of “seeing with the mind’s eye”. In the social domain, we imagine other individuals while recalling our encounters with them or modelling alternative social interactions in future. Many studies using imaging and neurophysiological techniques have shown several similarities in brain activity between visual imagery and visual perception, and have identified frontoparietal, occipital and temporal neural components of visual imagery. However, the neural connectivity between these regions during visual imagery of socially relevant stimuli have not been studied. Here we used electroencephalography to investigate neural connectivity and its dynamics between frontal, parietal, occipital and temporal electrodes during visual imagery of faces. We found that voluntary visual imagery of faces is associated with long-range phase synchronisation in the gamma frequency range between frontoparietal electrode pairs and between occipitoparietal electrode pairs. In contrast, no effect of imagery was observed in the connectivity between occipitotemporal electrode pairs. Gamma range synchronisation between occipitoparietal electrode pairs predicted subjective ratings of the contour definition of imagined faces. Furthermore, we found that visual imagery of faces is associated with an increase of short-range frontal synchronisation in the theta frequency range, which temporally preceded the long-range increase in the gamma synchronisation. We speculate that the local frontal synchrony in the theta frequency range might be associated with an effortful top-down mnemonic reactivation of faces. In contrast, the long-range connectivity in the gamma frequency range along the fronto-parieto-occipital axis might be related to the endogenous binding and subjective clarity of facial visual features.
Multiple incursion pathways forHelicoverpa armigerain Brazil show its genetic diversity spreading in a connected world
Authors: Arnemann Jonas A. , Roxburgh Stephen H. , Walsh Tom , Guedes Jerson V.C. , Gordon Karl H.J. , Smagghe Guy , Tay Wee Tek
Published: September 2019

The Old World cotton bollwormHelicoverpa armigerawas first detected in Brazil with subsequent reports from Paraguay, Argentina, Bolivia, and Uruguay. This pattern suggests that theH. armigeraspread across the South American continent following incursions into northern/central Brazil, however, this hypothesis has not been tested. Here we compare northern and central BrazilianH. armigeramtDNA COI haplotypes with those from southern Brazil, Uruguay, Argentina, and Paraguay. We infer spatial genetic and gene flow patterns of this dispersive pest in the agricultural landscape of South America. We show that the spatial distribution ofH. armigeramtDNA haplotypes and its inferred gene flow patterns in the southwestern region of South America exhibited signatures inconsistent with a single incursion hypothesis. Simulations on spatial distribution patterns show that the detection of rare and/or the absence of dominant mtDNA haplotypes in southernH. armigerapopulations are inconsistent with genetic signatures observed in northern and central Brazil. Incursions ofH. armigerainto the New World are therefore likely to have involved independent events in northern/central Brazil, and southern Brazil/Uruguay-Argentina-Paraguay. This study demonstrates the significant biosecurity challenges facing the South American continent, and highlights alternate pathways for introductions of alien species into the New World.
Ifnar1 signaling breaks the hepatic urea cycle to regulate adaptive immunity
Authors: Lercher Alexander , Bhattacharya Anannya , Popa Alexandra M. , Caldera Michael , Schlapansky Moritz F. , Baazim Hatoon , Majek Peter , Brunner Julia S. , Kosack Lindsay J. , Vitko Dijana , Pinter Theresa , Gürtl Bettina , Reil Daniela , Kalinke Ulrich , Bennett Keiryn L. , Menche Jörg , Cheng Paul N. , Schabbauer Gernot , Trauner Michael , Klavins Kristaps , Bergthaler Andreas
Published: September 2019

Infections induce complex host responses linked to antiviral defense, inflammation and tissue damage and repair. These processes are increasingly understood to involve systemic metabolic reprogramming. We hypothesized that the liver as a central metabolic hub may orchestrate many of these changes during infection. Thus, we investigated the systemic interplay between inflammation and metabolism in a mouse model of chronic viral infection and hepatitis. Here we show that virus-induced type I interferon (IFN-I) modulates wide-spread metabolic alterations of the liver in a hepatocyte-intrinsic Ifnar1-dependent way. Specifically, IFN-I repressed the transcription of numerous genes with metabolic function including Otc and Ass1, which encode enzymes of the urea cycle. This led to decreased arginine and increased ornithine concentrations in the circulation, resulting in suppressed virus-specific CD8 T cell responses and ameliorated liver pathology. These findings establish IFN-I-induced modulation of hepatic metabolism and the urea cycle as an endogenous mechanism of immunoregulation.
Thirty two novel nsSNPs May effect onHEXAprotein Leading to Tay-Sachs disease (TSD) Using a Computational Approach
Authors: Abdelhameed Tebyan A. , Osman Fadul Mohamed Mustafa , Abdelrahman Mohamed Dina Nasereldin , Mohamed Mudawi Amal , Fadul Allah Sayaf Kamal Khalifa , Elnour Ahmed Ola Ahmed , Idrees Mohammeddeen Sogoud Mohammednour , Taha khairi Aya Abdelwahab , Osman Soada Ahmed , Al-Hajj Ebrahim Mohammed , Elhag Mustafa , Hassan Salih Mohamed Ahmed
Published: September 2019

Background

Genetic polymorphisms in theHEXAgene are associated with a neurodegenerative disorder called Tay-Sachs disease (TSD) (GM2 gangliosidosis type 1). This study aimed to predict the possible pathogenic SNPs of this gene and their impact on the protein using different bioinformatics tools.

Methods

SNPs retrieved from the NCBI database were analyzed using several bioinformatics tools. The different algorithms collectively predicted the effect of single nucleotide substitution on both structure and function of the hexosaminidase A protein.

Results

Fifty nine mutations were found to be highly damaging to the structure and function of theHEXAgene protein.

Conclusion

According to this study, thirty two novel nsSNP inHEXAare predicted to have possible role in Tay-Saches Disease using different bioinformatics tools. Our findings could help in genetic study and diagnosis of Tay-Saches Disease.
High pressure inhibits signaling protein binding to the flagellar motor and bacterial chemotaxis through enhanced hydration
Authors: Hata Hiroaki , Nishihara Yasutaka , Nishiyama Masayoshi , Sowa Yoshiyuki , Kawagishi Ikuro , Kitao Akio
Published: September 2019

In the chemotaxis ofEscherichia coli, the cell’s behavioral switch involves binding of the phosphorylated form of the chemotaxis signaling protein CheY (CheYp) to the flagellar motor protein FliM, which induces the motor to rotate clockwise; otherwise, the motor rotates counterclockwise. To investigate high-pressure effects on CheYp–FliM binding at atomic resolution, we conduct molecular dynamics simulations of monomeric CheYp, the N-terminal fragment of the FliM (FliMN) that binds to CheYp, and the complex that forms between those proteins at pressures ranging from 0.1 to 100 MPa. The results show that the active form of monomeric CheYp is maintained even at 100 MPa but high pressure increases the water density in the first hydration shell and can cause conformational change of the C-terminal helix. The dissociation process of the complex is investigated by parallel cascade selection molecular dynamics (PaCS-MD), revealing that high pressure considerably induces water penetration into the complex interface. Pressure dependence of standard binding free energy calculated by the Markov state model indicates that the increase of pressure from 0.1 to 100 MPa weakens the binding by ∼ 10 kcal/mol. Using high-pressure microscopy, we observed that high hydrostatic pressure reversibly fixes the motor rotation in the counter-clockwise orientation, which supports the notion that high pressure inhibits the binding of CheYp to FliM. We conclude that high pressure induces water penetration into the complex interface, which interferes with CheYp–FliM binding and prevents motor reversal.
Annual replication is essential in evaluating the response of the soil microbiome to the genetic modification of maize in different biogeographical regions
Authors: Szoboszlay Márton , Näther Astrid , Mullins Ewen , Tebbe Christoph C.
Published: September 2019

The importance of geographic location and annual variation on the detection of differences in the rhizomicrobiome caused by the genetic modification of maize (Bt-maize, event MON810) was evaluated at experimental field sites across Europe including Sweden, Denmark, Slovakia and Spain. DNA of the rhizomicrobiome was collected at the maize flowering stage in three consecutive years and analyzed for the abundance and diversity of PCR-amplified structural genes ofBacteria,ArchaeaandFungi, and functional genes for bacterial nitrite reductases (nirS,nirK). ThenirKgenes were always more abundant thannirS. Maize MON810 did not significantly alter the abundance of any microbial genetic marker, except for sporadically detected differences at individual sites and years. In contrast, annual variation between sites was often significant and variable depending on the targeted markers. Distinct, site-specific microbial communities were detected but the sites in Denmark and Sweden were similar to each other. A significant effect of the genetic modification of the plant on the community structure in the rhizosphere was detected among thenirKdenitrifiers at the Slovakian site in only one year. However, mostnirKsequences with opposite response were from the same or related source organisms suggesting that the transient differences in community structure did not translate to the functional level. Our results show a lack of effect of the genetic modification of maize on the rhizosphere microbiome that would be stable and consistent over multiple years. This demonstrates the importance of considering annual variability in assessing environmental effects of genetically modified crops.
Convolutional neural networks for mild diabetic retinopathy detection: an experimental study
Authors: Sarki Rubina , Michalska Sandra , Ahmed Khandakar , Wang Hua , Zhang Yanchun
Published: September 2019

Currently, Diabetes and the associated Diabetic Retinopathy (DR) instances are increasing at an alarming rate. Numerous previous research has focused on automated DR detection from fundus photography. The classification ofseverecases of pathological indications in the eye has achieved over 90% accuracy. Still, themildcases are challenging to detect due to CNN inability to identify the subtle features, discrimnative of disease. The data used (i.e. annotated fundus photographies) was obtained from 2 publicly available sources – Messidor and Kaggle. The experiments were conducted with 13 Convolutional Neural Networks architectures, pre-trained on large-scale ImageNet database using the concept of Transfer Learning. Several performance improvement techniques were applied, such as: (i) fine-tuning, (ii) data augmentation, and (iii) volume increase. The results were measured against the standard Accuracy metric on the testing dataset. After the extensive experimentation, the maximum Accuracy of 86% on No DR/Mild DR classification task was obtained forResNet50model with fine-tuning (un-freeze and re-train the layers from 100 onwards), and RMSProp Optimiser trained on the combined Messidor + Kaggle (aug) datasets. Despite promising results, Deep learning continues to be an empirical approach that requires extensive experimentation in order to arrive at the most optimal solution. The comprehensive evaluation of numerous CNN architectures was conducted in order to facilitate an early DR detection. Furthermore, several performance improvement techniques were assessed to address the CNN limitation in subtle eye lesions identification. The model also included various levels of image quality (low/high resolution, under/over-exposure, out-of-focus etc.), in order to prove its robustness and ability to adapt to real-world conditions.
Efficacy of aerial forward-looking infrared surveys for detecting polar bear maternal dens
Authors: Smith Tom S. , Amstrup Steven C. , Kirschhoffer John , York Geoffrey
Published: September 2019

Denned polar bears are invisible under the snow, therefore winter-time petroleum exploration and development activities in northern Alaska have potential to disturb maternal polar bears and their cubs. Previous research determined forward looking infrared (FLIR) imagery could detect many polar bear maternal dens under the snow, but also identified limitations of FLIR imagery. We evaluated the efficacy of FLIR-surveys conducted by oil-field operators from 2004-2016. Aerial FLIR surveys detected 15 of 33 (45%) and missed 18 (55%) of the dens known to be within surveyed areas. While greater adherence to previously recommended protocols may improve FLIR detection rates, the physical characteristics of polar bear maternal dens, increasing frequencies of weather unsuitable for FLIR detections—caused by global warming, and competing “hot spots” are likely to prevent FLIR surveys from detecting maternal dens reliably enough to afford protections consonant with increasing global threats to polar bear welfare.
A simple pyrocosm for studying soil microbial response to fire reveals a rapid, massive response byPyronemaspecies
Authors: Bruns Thomas D. , Chung Judy A. , Carver Akiko A. , Glassman Sydney I.
Published: September 2019

We have designed a simple, inexpensive system for the studying the response of soil microbes to fire. This system allows one to create post-fire environments in soil in reproducible and realistic ways. Using it we show that the peak soil temperature achieved at a given depth occurs hours after the fire is out, lingers near peak temperature for a significant time, and is accurately predicted by the log of soil depth and the mass charcoal burned. Flash fuels that left no large coals were found to have a negligible soil heating effect. Coupling this system with Illumina MiSeq sequencing of the control and post-fire soil we show that we can stimulate a rapid, massive response byPyronema, a well-known genus of postfire fungus, from uninoculated forest soil within two weeks of a test fire. This specific stimulation occurs in a background of many other fungal taxa that do not change significantly with the fire, although there is an overall reduction in richness and evenness. Extrapolating from the physical relationships we predict soil heating effects in wild fires are likely to be very patchy across the forest floor but the width of a survivable “goldilocks zone” will stay relatively constant across a range of fuel loads. We further predict that a necromass zone above it, which represents an open niche for pyrophilous microbes, increases in size rapidly with addition of fuel, and then remains nearly constant over a broad range of fuel loads. The simplicity of this experimental system, coupled with the availability of a set of sequenced, assembled and annotated genomes of pyrophilous fungi, offers a powerful tool for dissecting the ecology of post-fire microbial communities.
Inhibiting the copper efflux system in microbes as a novel approach for developing antibiotics
Authors: Meir Aviv , Lepechkin-Zilbermintz Veronica , Kahremany Shirin , Schwerdtfeger Fabian , Gevorkyan-Airapetov Lada , Munder Anna , Viskind Olga , Gruzman Arie , Ruthstein Sharon
Published: September 2019

Five out of six people receive at least one antibiotic prescription per year. However, the ever-expanding use of antibiotics in medicine, agriculture, and food production has accelerated the evolution of antibiotic-resistant bacteria, which, in turn, made the development of novel antibiotics based on new molecular targets a priority in medicinal chemistry. One way of possibly combatting resistant bacterial infections is by inhibiting the copper transporters in prokaryotic cells. Copper is a key element within all living cells, but it can be toxic in excess. Both eukaryotic and prokaryotic cells have developed distinct copper regulation systems to prevent its toxicity. Therefore, selectively targeting the prokaryotic copper regulation system might be an initial step in developing next-generation antibiotics. One such system is the Gram-negative bacterial CusCFBA efflux system. CusB is a key protein in this system and was previously reported to play an important role in opening the channel for effluxviasignificant structural changes upon copper binding while also controlling the assembly and disassembly process of the entire channel. In this study, we aimed to develop novel peptide copper channel blockers, designed byin silicocalculations based on the structure of CusB. Using a combination of magnetic resonance spectroscopy and various biochemical methods, we found a lead peptide that promotes copper-induced cell toxicity. Targeting copper transport in bacteria has not yet been pursued as an antibiotic mechanism of action. Thus, our study lays the foundation for discovering novel antibiotics.

Author Summary

Herein, we apply a novel approach for the development of a new generation of antibiotics based on copper toxicity. In cells, copper ions are double-edge swords. On the one hand, various enzymes depend on them as cofactors for catalysis, but on the other hand, they are highly toxic. Thus, cells have developed sophisticated regulation systems to very precisely control copper concentration. Prokaryotic organisms are more sensitive to copper than eukaryotic systems, and therefore they employ additional copper transporters that have no homology in the eukaryotic cells in general and specifically in the human cell. Here, we suggest to take advantage of this fact, by developing inhibitors against one of the bacterial copper transporter: CusCBA. The adaptor protein within this transporter, CusB, plays a critical role in the opening of the whole transporter. We designed a peptide that interfere with its proper function and assembly, and therefore inhibits the opening of the transporter upon copper stress. This study lays the foundation for designing better and novel antibiotics.
The role of the diencephalon in the guidance of thalamocortical axons in mice
Authors: Quintana-Urzainqui Idoia , Pablo Hernández-Malmierca P , Clegg James M. , Li Ziwen , Kozić Zrinko , Price David J
Published: September 2019

Thalamocortical axons (TCAs) cross several tissues on their journey to the cortex. Mechanisms must be in place along the route to ensure they connect with their targets in an orderly fashion. The ventral telencephalon acts as an instructive tissue, but the importance of the diencephalon in TCA mapping is unknown. We report that disruption of diencephalic development by Pax6 deletion results in a thalamocortical projection containing mapping errors. We used conditional mutagenesis to test whether these errors are due to the disruption of pioneer projections from prethalamus to thalamus and found that, while this correlates with abnormal TCA fasciculation, it does not induce topographical errors. To test whether the thalamus contains navigational cues for TCAs, we used slice culture transplants and gene expression studies. We found the thalamic environment is instructive for TCA navigation and that the molecular cues Netrin1 and Semaphorin3a are likely to be involved. Our findings indicate that the correct topographic mapping of TCAs onto the cortex requires the order to be established from the earliest stages of their growth by molecular cues in the thalamus itself.
NHJ-1 regulates canonical non-homologous end joining inCaenorhabditis elegans
Authors: Vujin Aleksandar , Jones Steven J. , Zetka Monique
Published: September 2019

Canonical non-homologous end joining (cNHEJ) is a near-universally conserved pathway for the repair of DNA double-strand breaks (DSBs). While the cNHEJ pathway encompasses more than a dozen factors in vertebrates and is similarly complex in other eukaryotes, in the nematodeC. elegansthe entire known cNHEJ toolkit consists of two proteins that comprise the Ku ring complex,cku-70andcku-80, and the terminal ligaselig-4. Here, we report the discovery ofnhj-1as the fourth cNHEJ factor inC. elegans. Observing a difference in the phenotypic response to ionizing radiation (IR) between two lines of the wild type N2 strain, we mapped the locus causative of IR-sensitivity to a candidate on chromosome V. Using CRISPR-Cas9 mutagenesis, we show that disrupting thenhj-1sequence induces IR-sensitivity in an IR-resistant background. Double mutants ofnhj-1and the cNHEJ factorslig-4orcku-80do not exhibit additive IR-sensitivity, arguing thatnhj-1is a member of the cNHEJ pathway. Furthermore, like the loss oflig-4,the loss ofnhj-1in thecom-1genetic background, in which meiotic DSBs are repaired by cNHEJ instead of homologous recombination, increased the number of DAPI-staining bodies in diakinesis, consistent with increased chromosome fragmentation in the absence of cNHEJ repair. Finally, we show that NHJ-1 localizes to many somatic nuclei in the L1 larva, but not the primordial germline, which is in accord with a role in the predominantly somatically active cNHEJ. Althoughnhj-1shares no sequence homology with other known eukaryotic cNHEJ factors and is taxonomically restricted to the Rhadbitid family, its discovery underscores the evolutionary plasticity of even highly conserved pathways, and may represent a springboard for further characterization of cNHEJ inC. elegans.