bluuebunny/crossref_metadata_2025 huggingface dataset:
Phosphine: an eco-friendly alternative for management of wheat storage insects
Authors: Arora Sumitra , Stanley J. , Srivastava C.
Published: March 2020

Methyl bromide (MB) fumigant has been phased out in many countries honouring ‘Montreal Protocol’. Reports on phosphine fumigant efficacy under different ecological zones in India are scanty. Field fumigation trials were conducted on 5 Metric Tons of wheat stacks per replication of a treatment for testing phosphine efficacy against laboratory cultured and resident population ofTribolium castanium,Sitophilus oryzae, andRhyzopertha dominica. The trials were organized in triplicate including control at two locations with varying climate locations namely, Pithoragarh and Delhi using conventional 56% tablet (2 and 3 tablet/MT) and 77.5% granular (1.0 and 1.5 g phosphine/m3) formulations of Aluminium phosphide (AlP) for 7 and 10-days exposure periods for each dosage. Phosphine concentration was monitored every 24 hours till end of the exposure periods. Insect mortality of laboratory culture and resident infestation was observed as 100% in both the exposure periods using all dosages of phosphine. No emergence of insects was observed till 60 days after treatment at both the locations, indicating mortality of all available life stages of insects during the exposure periods. Minimum effective phosphine concentration for controlling all life stages ofS. oryzae,R. dominicaandT castaneumwas observed 500-600 ppm for 7-days exposure at 25°-27°C and humidity 38-45%, at 1.5 g phosphine/m3. Hence, phosphine can be an effective alternative to methyl bromide fumigant for wheat stored grain insects at different climatic conditions.
ACTB and GAPDH proteins appear at multiple positions of SDS-PAGE and may not be suitable for serving as reference genes for the protein level determination in such techniques as Western blotting
Authors: He Yan , Zhang Ju , Qu Jiayuan , Zellmer Lucas , Zhao Yan , Liu Siqi , Huang Hai , Liao Dezhong Joshua
Published: March 2020

Most human genes can produce multiple protein isoforms that should appear at multiple positions of polyacrylamide gel electrophoresis (PAGE) with sodium dodecyl sulfate (SDS), but most published results of Western blotting show only one protein. We performed SDS-PAGE of proteins from several human cell lines, isolated the proteins at the 72-, 55-, 48-, 40-, and 26-kD positions, and used liquid chromatography and tandem mass spectrometry (LC-MS/MS) to determine the protein identities. Although ACTB and GAPDH are 41.7-kD and 36-kD proteins, respectively, LC-MS/MS identified peptides of ACTB and GAPDH at all of these SDS-PAGE positions, making us wonder whether they produce some unknown protein isoforms. The NCBI (National Center for Biotechnology Information, USA) database lists only one ACTB mRNA but five GAPDH mRNAs and one non-coding RNA. The five GAPDH mRNAs encode three protein isoforms, while our bioinformatic analysis identified a 17.6-kD isoform encoded by the non-coding RNA. All LC-MS/MS-identified GAPDH peptides at all positions studied are unique, but some of the identified ACTB peptides are shared by ACTC1, ACTBL2, POTEF, POTEE, POTEI, and POTEJ. ACTC1 and ACTBL2 belong to the ACT family with great similarities to ACTB in protein sequence, whereas the four POTEs are ACTB-containing chimeric genes with the C-terminus of their proteins highly similar to ACTB. These data collectively disqualify GAPDH and ACTB from serving as the reference genes for determination of the protein level in such techniques as Western blotting, a leading role these two genes have been playing for decades in the biomedical research.
Epizootic of highly pathogenic H7N3 Avian Influenza in an ecologic reserve in Mexico
Authors: Navarro-López Roberto , Solís-Hernández Mario , Márquez-Ruiz Miguel A. , Rosas-Téllez Abel , Guichard-Romero Carlos A. , Cartas-Heredia Gerardo de J. , Morales-Espinosa Romeo , Valdez-Gómez Héctor E. , Afonso Claudio L.
Published: March 2020

This report includes a 2015 epizootic of highly pathogenic H7N3 avian influenza virus among captive and wild birds at “El Zapotal” ecologic reserve, located in the state of Chiapas, Mexico. Epidemiological control measures were implemented to prevent virus dissemination. The infection with the highly pathogenic H7N3 virus was detected predominantly among Plain Chachalaca (Ortalis vetula), with occasional detections in a White-fronted Parrot (Amazona albifrons) and a single Clay-colored Thrush (Turdus grayi). Here, we describe the characteristics of the outbreak environment, the surveillance strategy, the biosecurity measures, and the evaluation of the site, including external farms. These actions, timely implemented by the veterinary authorities, helped to contain the outbreak beyond the ecologic reserve. This contingency showed the importance of developing a more complete analysis of the existing risks and the challenges to implement minimal biosecurity measures in these facilities.
NORMA-The network makeup artist: a web tool for network annotation visualization
Authors: Koutrouli Mikaela , Karatzas Evangelos , Papanikolopoulou Katerina , Pavlopoulos Georgios A.
Published: March 2020

NORMA is a web tool for interactive network annotation visualization and topological analysis, able to handle multiple networks and annotations simultaneously. Precalculated annotations (e.g. Gene Ontology/Pathway enrichment or clustering results) can be uploaded and visualized in a network either as colored pie-chart nodes or as color-filled convex hulls in a Venn-diagram-like style. In the case where no annotation exists, algorithms for automated community detection are offered. Users can adjust the network views using standard layout algorithms or allow NORMA to slightly modify them for visually better group separation. Once a network view is set, users can interactively select and highlight any group of interest in order to generate publication-ready figures. Briefly, with NORMA, users can encode three types of information simultaneously. These are:i)the network,ii)the communities or annotations andiii)node categories or expression values. Finally, NORMA offers basic topological analysis and direct topological comparison across any of the selected networks. NORMA service is available at:http://bib.fleming.gr:3838/NORMAorhttp://genomics-lab.fleming.gr:3838/NORMA. Code is available at:https://github.com/PavlopoulosLab/NORMA
Phenotype Prediction using a Tensor Representation and Deep Learning from Data Independent Acquisition Mass Spectrometry
Authors: Zhang Fangfei , Yu Shaoyang , Wu Lirong , Zang Zelin , Yi Xiao , Zhu Jiang , Lu Cong , Sun Ping , Sun Yaoting , Selvarajan Sathiyamoorthy , Chen Lirong , Teng Xiaodong , Zhao Yongfu , Wang Guangzhi , Xiao Junhong , Huang Shiang , Kon Oi Lian , Iyer N. Gopalakrishna , Li Stan Z. , Luan Zhongzhi , Guo Tiannan
Published: March 2020

A novel approach for phenotype prediction is developed for mass spectrometric data. First, the data-independent acquisition (DIA) mass spectrometric data is converted into a novel file format called “DIA tensor” (DIAT) which contains all the peptide precursors and fragments information and can be used for convenient DIA visualization. The DIAT format is fed directly into a deep neural network to predict phenotypes without the need to identify peptides or proteins. We applied this strategy to a collection of 102 hepatocellular carcinoma samples and achieved an accuracy of 96.8% in classifying malignant from benign samples. We further applied refined model to 492 samples of thyroid nodules to predict thyroid cancer; and achieved a predictive accuracy of 91.7% in an independent cohort of 216 test samples. In conclusion, DIA tensor enables facile 2D visualization of DIA proteomics data as well as being a new approach for phenotype prediction directly from DIA-MS data.
Model-based design and analysis of life table experiments for insect vectors
Authors: Erguler Kamil , Demirok Murat Can , Gunay Filiz , Petrić Mina , Kavran Mihaela , Petrić Dušan Veljko , Alten Bulent
Published: March 2020

Life tables help identify physiological differences in distinct development stages and detect potential vulnerabilities for conservation and control. However, cataloguing mortality, development, and fecundity by following each individual could be challenging in insects due to interweaving generations and development stages.

Here, we propose to use age- and stage-structured population dynamics modelling to help derive life table characteristics from the observed dynamics of reared populations. We examine a hypothetical case, a simulated population with known life parameters, and two experimental cases, observations of the population dynamics of the mosquito vectorsCulex quinquefasciatusandCulex pipiens, to demonstrate that model-based inference can correctly identify life parameters from longitudinal observations. The analysis reveals not only the differential physiological behaviour of distinct development stages, but also identifies the degree to which each parameter can be inferred from the data.

The methods introduced constitute a model-based approach to identifying life table characteristics from incomplete longitudinal data, and help to improve the design of life table experiments. The approach is readily applicable to the development of climate- and environment-driven population dynamics models for important vectors of disease.
ProminTools: Shedding light on proteins of unknown function in biomineralization with user friendly tools illustrated using mollusc shell matrix protein sequences
Authors: Skeffington Alastair W , Donath Andreas
Published: March 2020

Biominerals are crucial to the fitness of many organism and studies of the mechanisms of biomineralization are driving research into novel materials. Biomineralization is generally controlled by a matrix of organic molecules including proteins, so proteomic studies of biominerals are important for understanding biomineralization mechanisms. Many such studies identify large numbers of proteins of unknown function, which are often of low sequence complexity and biased in their amino acid composition. A lack of user-friendly tools to find patterns in such sequences and robustly analyse their statistical properties relative to the background proteome means that they are often neglected in follow-up studies. Here we present ProminTools, a user-friendly package for comparison of two sets of protein sequences in terms of their global properties and motif content. Outputs include data tables, graphical summaries in an html file and an R-script as a starting point for data-set specific visualizations. We demonstrate the utility of ProminTools using a previously published shell matrix proteome of the giant limpetLottia gigantea.
Time of Day Dependent Effects of Contractile Activity on the Phase of the Skeletal Muscle Clock
Authors: Kemler Denise , Wolff Christopher A. , Esser Karyn A.
Published: March 2020

Exercise has been proposed to be a zeitgeber for the muscle circadian clock mechanism. However, this is not well defined and it is unknown if exercise timing induces directional shifts of the muscle clock. Our purpose herein was to assess the effect of one bout of treadmill exercise on skeletal muscle clock phase changes. We subjected PERIOD2::LUCIFERASE mice (n=30F) to one 60-minute treadmill exercise bout at three times of day. Exercise at ZT5, 5h after lights on, induced a phase advance (1.4±0.53h; p=0.038), whereas exercise at ZT11, 1h before lights off, induced a phase delay (−0.95±0.43h; p=0.0315). Exercise at ZT17, middle of the dark phase, did not alter muscle clock phase. Exercise induces diverse systemic changes so we developed anin-vitromodel system to examine effects of contractile activity on muscle clock phase. Contractions applied at peak or troughBmal1expression induced significant phase delays (applied at peak: 1.3±0.02h; p=0.0425; applied at trough: 1.8±0.02h, p=0.0074). Contractions applied during the transition from peak to troughBmal1expression induced a phase advance (1.8±0.03h; p=0.0265). Lastly, contractions at different times of day resulted in differential changes of core-clock gene expression demonstrating an exercise and clock interaction, providing insight into potential mechanisms exercise-induced phase shifts. These data demonstrate that muscle contractions, as part of exercise, are sufficient to shift muscle circadian clock phase, likely through changes in core-clock gene expression. Additionally, our findings that exercise induces directional muscle clock phase changes confirms exercise is a bone fide environmental time cue for skeletal muscle.
Modification of forests by people means only 40% of remaining forests have high ecosystem integrity
Authors: Grantham H.S. , Duncan A. , Evans T. D. , Jones K. , Beyer H. , Schuster R. , Walston J. , Ray J. , Robinson J. , Callow M. , Clements T. , Costa H.M. , DeGemmis A. , Elsen P.R. , Ervin J. , Franco P. , Goldman E. , Goetz S. , Hansen A. , Hofsvang E. , Jantz P. , Jupiter S. , Kang A. , Langhammer P. , Laurance W.F. , Lieberman S. , Linkie M. , Malhi Y. , Maxwell S. , Mendez M. , Mittermeier R. , Murray N. , Possingham H. , Radachowsky J. , Samper C. , Silverman J. , Shapiro A. , Strassburg B. , Stevens T. , Stokes E. , Taylor R. , Tear T. , Tizard R. , Venter O. , Visconti P. , Wang S. , Watson J.E.M.
Published: March 2020

Many global environmental agendas, including halting biodiversity loss, reversing land degradation, and limiting climate change, depend upon retaining forests with high ecological integrity, yet the scale and degree of forest modification remains poorly quantified and mapped. By integrating data on observed and inferred human pressures and an index of lost connectivity, we generate the first globally-consistent, continuous index of forest condition as determined by degree of anthropogenic modification. Globally, only 17.4 million km2of forest (40.5%) have high landscape level integrity (mostly found in Canada, Russia, the Amazon, Central Africa and New Guinea) and only 27% of this area is found in nationally-designated protected areas. Of the forest in protected areas, only 56% has high landscape level integrity. Ambitious policies that prioritize the retention of forest integrity, especially in the most intact areas, are now urgently needed alongside current efforts aimed at halting deforestation and restoring the integrity of forests globally.
miEAA 2.0: Integrating multi-species microRNA enrichment analysis and workflow management systems
Authors: Kern Fabian , Fehlmann Tobias , Solomon Jeffrey , Schwed Louisa , Backes Christina , Meese Eckart , Keller Andreas
Published: March 2020

Gene set enrichment analysis has become one of the most frequently used applications in molecular biology research. Originally developed for gene sets, the same statistical principles are now available for all omics types. In 2016, we published the miRNA enrichment analysis and annotation tool (miEAA) for human precursor and mature miRNAs.

Here, we present miEAA 2.0, supporting miRNA input fromHomo sapiens, Mus musculus, andRattus norvegicus. To facilitate inclusion of miEAA in workflow systems, we implemented an Application Programming Interface (API). Users can perform miRNA set enrichment analysis using either the web-interface, a dedicated Python package, or custom remote clients. Moreover, the number of category sets was raised by an order of magnitude. We implemented novel categories like annotation confidence level or localisation in biological compartments. In combination with the miR-Base miRNA-version and miRNA-to-precursor converters, miEAA supports research settings where older releases of miRBase are in use. The web server also offers novel comprehensive visualisations such as heatmaps and running sum curves with background distributions. Lastly, additional methods to correct for multiple hypothesis testing were implemented. We demonstrate the new features using case studies for human kidney cancer and mouse samples. The tool is freely accessible at:https://www.ccb.uni-saarland.de/mieaa2.
SIZ1-mediated SUMOylation of ROS1 Enhances Its Stability and Positively Regulates Active DNA Demethylation inArabidopsis
Authors: Kong Xiangfeng , Hong Yechun , Hsu Yi-Feng , Huang Huan , Liu Xue , Song Zhe , Zhu Jian-Kang
Published: March 2020

The 5-methylcytosine DNA glycosylase/lyase REPRESSOR OF SILENCING 1 (ROS1)-mediated active DNA demethylation is critical for shaping the genomic DNA methylation landscape inArabidopsis. Whether and how the stability of ROS1 may be regulated by post-translational modifications is unknown. Using a methylation-sensitive PCR (CHOP-PCR)-based forward genetic screen forArabidopsisDNA hypermethylation mutants, we identified the SUMO E3 ligase SIZ1 as a critical regulator of active DNA demethylation. Dysfunction of SIZ1 leads to hyper-methylation at approximately one thousand genomic regions. SIZ1 physically interacts with ROS1 and mediates the SUMOylation of ROS1. The SUMOylation of ROS1 is reduced insiz1mutant plants. Compared to that in wild type plants, the protein level of ROS1 is significantly decreased, even though there is an increased level ofROS1transcripts insiz1mutant plants. Our results suggest that SIZ1 positively regulates active DNA demethylation by promoting the stability of ROS1 protein through SUMOylation.

Short Summary

The 5-methylcytosine DNA glycosylase/lyase REPRESSOR OF SILENCING 1 (ROS1) is indispensable for proper DNA methylation landscape inArabidopsis. Whether and how the stability of ROS1 may be regulated by post-translational modifications is unknown. Here, we show that SIZ1-mediated SUMOylation of ROS1 enhances its stability and positively regulates active DNA demethylation.
Quaternionic Assessment of EEG Traces on Nervous Multidimensional Hyperspheres
Authors: Tozzi Arturo , Peters James F. , Jausovec Norbert , Legchenkova Irina , Bormashenko Edward
Published: March 2020

The nervous activity of the brain takes place in higher-dimensional functional spaces. Indeed, recent claims advocate that the brain might be equipped with a phase space displaying four spatial dimensions plus time, instead of the classical three plus time. This suggests the possibility to investigate global visualization methods for exploiting four-dimensional maps of real experimental data sets. Here we asked whether, starting from the conventional neuro-data available in three dimensions plus time, it is feasible to find an operational procedure to describe the corresponding four-dimensional trajectories. In particular, we used quaternion orthographic projections for the assessment of electroencephalographic traces (EEG) from scalp locations. This approach makes it possible to map three-dimensional EEG traces to the surface of a four-dimensional hypersphere, which has an important advantage, since quaternionic networks make it feasible to enlighten temporally far apart nervous trajectories equipped with the same features, such as the same frequency or amplitude of electric oscillations. This leads to an incisive operational assessment of symmetries, dualities and matching descriptions hidden in the very structure of complex neuro-data signals.
Chromatin Topology Reorganization and Transcription Repression by PML/RARα in Acute Promyeloid Leukemia
Authors: Wang Ping , Tang Zhonghui , Lee Byoungkoo , Zhu Jacqueline Jufen , Cai Liuyang , Szalaj Przemyslaw , Tian Simon Zhongyuan , Zheng Meizhen , Plewczynski Dariusz , Ruan Xiaoan , Liu Edison T. , Wei Chia-Lin , Ruan Yijun
Published: March 2020

Background

Acute promyeloid leukemia (APL) is characterized by the oncogenic fusion protein PML/RARα, a major etiological agent in APL. However, the molecular mechanisms underlying the role of PML/RARα in leukemogenesis remains largely unknown.

Results

Using an inducible system, we comprehensively analyzed the 3D genome organization in myeloid cells and its reorganization after PML/RARα induction, and performed additional analyses in patient-derived APL cells with native PML/RARα. We discovered that PML/RARα mediates extensive chromatin interactions genome-wide. Globally, it redefines the chromatin topology of the myeloid genome toward a more condensed configuration in APL cells; locally, it intrudes RNAPII-associated interaction domains, interrupts myeloid-specific transcription factors binding at enhancers and super-enhancers, and leads to transcriptional repression of genes critical for myeloid differentiation and maturation.

Conclusions

Our results not only provide novel topological insights for the roles of PML/RARα in transforming myeloid cells into leukemia cells, but further uncover a topological framework of a molecular mechanism for oncogenic fusion proteins in cancers.
Loop detection using Hi-C data with HiCExplorer
Authors: Wolff Joachim , Backofen Rolf , Grüning Björn
Published: March 2020

Chromatin loops are an important factor in the structural organization of the genome. The detection of chromatin loops in Hi-C interaction matrices is a challenging and compute intensive task. The presented approach shows a chromatin loop detection algorithm which applies a strict candidate selection based on continuous negative binomial distributions and performs a Wilcoxon rank-sum test to detect enriched Hi-C interactions.
Bayesian Genome-wide TWAS method to leverage both cis- and trans- eQTL information through summary statistics
Authors: Luningham Justin M. , Chen Junyu , Tang Shizhen , De Jager Philip L. , Bennett David A. , Buchman Aron S. , Yang Jingjing
Published: March 2020

Transcriptome-wide association studies (TWAS) have been widely used to integrate gene expression and genetic data for studying complex traits. Due to the computational burden, existing TWAS methods do not assess distant trans- expression quantitative trait loci (eQTL) that are known to explain important expression variation for most genes. We propose a Bayesian Genome-wide TWAS (BGW-TWAS) method which leverages both cis- and trans- eQTL information for TWAS. Our BGW-TWAS method is based on Bayesian variable selection regression, which not only accounts for cis- and trans- eQTL of the target gene but also enables efficient computation by using summary statistics from standard eQTL analyses. Our simulation studies illustrated that BGW-TWAS achieved higher power compared to existing TWAS methods that do not assess trans-eQTL information. We further applied BWG-TWAS to individual-level GWAS data (N=∼3.3K), which identified significant associations between the genetically regulated gene expression (GReX) of geneZC3H12Band Alzheimer’s dementia (AD) (p-value= 5.42 × 10−13), neurofibrillary tangle density (p-value= 1.89 ×10−6), and global measure of AD pathology (p-value=9.59 × 10−7). These associations for geneZC3H12Bwere completely driven by trans-eQTL. Additionally, the GReX of geneKCTD12was found to be significantly associated withβ-amyloid (p-value= 3.44 ×10−8) which was driven by both cis- and trans- eQTL. Four of the top driven trans-eQTL ofZC3H12Bare located within geneAPOC1, a known major risk gene of AD and blood lipids. Additionally, by applying BGW-TWAS with summary-level GWAS data of AD (N=∼54K), we identified 13 significant genes including known GWAS risk genesHLA-DRB1andAPOC1, as well asZC3H12B.
Cell-free styrene biosynthesis at high titers
Authors: Grubbe William S. , Rasor Blake J. , Krüger Antje , Jewett Michael C. , Karim Ashty S.
Published: March 2020

Styrene is an important petroleum-derived molecule that is polymerized to make versatile plastics, including disposable silverware and foamed packaging materials. Finding more sustainable methods, such as biosynthesis, for producing styrene is essential due to the increasing severity of climate change as well as the limited supply of fossil fuels. Recent metabolic engineering efforts have enabled the biological production of styrene inEscherichia coli, but styrene toxicity and volatility limit biosynthesis in cells. To address these limitations, we have developed a cell-free styrene biosynthesis platform. The cell-free system provides an open reaction environment without cell viability constraints, which allows exquisite control over reaction conditions and greater carbon flux toward product formation rather than cell growth. The two biosynthetic enzymes required for styrene production were generated via cell-free protein synthesis and mixed in defined ratios with supplemented L-phenylalanine and buffer. By altering the time, temperature, pH, and enzyme concentrations in the reaction, this approach increased the cell-free titer of styrene from 5.36 ± 0.63 mM to 40.33 ± 1.03 mM, an order of magnitude greater than cellular synthesis methods. Cell-free systems offer a complimentary approach to cellular synthesis of small molecules, which can provide particular benefits for producing toxic molecules.

Highlights

A cell-free system for styrene biosynthesis was established. Thisin vitrosystem achieved styrene titers an order of magnitude greater than the highest reported concentrationin vivo.
Excess entropies reveal higher organization levels in developing neuron cultures
Authors: Stoop Norbert , Stoop Ralph L. , Kanders Karlis , Stoop Ruedi
Published: March 2020

Multi-component systems often exhibit dynamics of a high degree of complexity, rendering it difficult to assess whether a proposed model’s description is adequate. For the multitude of systems that allow for a symbolic encoding, we provide a symbolic-dynamics based entropy measure that quantifies the degree of deviation obtained by a systems’s internal dynamics from random dynamics using identical average symbol probabilities. We apply this measure to several well-studied theoretical models and show its ability to characterize differences in internal dynamics, thus providing a means to accurately compare model and experiment. Data from neuronal cultures on a multi-electrode array chip validate the usefulness of our approach, revealing inadequacies of existing models and providing guidelines for their improvement. We propose our measure to be systematically used to develop future models and simulations.
Improved stability of an engineered function using adapted bacterial strains
Authors: Tack Drew S. , Tonner Peter D. , Musteata Elena , Paralanov Vanya , Ross David
Published: March 2020

Engineering useful functions into cells is one of the primary goals of synthetic biology. However, engineering novel functions that remain stable for multiple generations remains a significant challenge. Here we report the importance of host fitness on the stability of an engineered function. We find that the initial fitness of the host cell affects the stability of the engineered function. We demonstrate that adapting a strain to the intended growth condition increases fitness and in turn improves the stability of the engineered function over hundreds of generations. This approach offers a simple and effective method to increase the stability of engineered functions without genomic modification or additional engineering and will be useful in improving the stability of novel, engineered functions in living cells.

Abstract Figure
Discovery and Predictive Modeling of Urine Microbiome, Metabolite and Cytokine Biomarkers in Hospitalized Patients with Community Acquired Pneumonia
Authors: Pierre Joseph F. , Akbilgic Oguz , Smallwood Heather , Cao Xueyuan , Fitzpatrick Elizabeth A. , Pena Senen , Furmanek Stephen P. , Ramirez Julio A. , Jonsson Colleen B
Published: March 2020

Pneumonia is the leading cause of infectious related death costing 12 billion dollars annually in the United States alone. Despite improvements in clinical care, total mortality remains around 4%, with inpatient mortality reaching 5-10%. For unknown reasons, mortality risk remains high even after hospital discharge and there is a need to identify those patients most at risk. Also of importance, clinical symptoms alone do not distinguish viral from bacterial infection which may delay appropriate treatment and may contribute to short-term and long-term mortality. Biomarkers have the potential to provide point of care diagnosis, identify high-risk patients, and increase our understanding of the biology of disease. However, there have been mixed results on the diagnostic performance of many of the analytes tested to date. Urine represents a largely untapped source for biomarker discovery and is highly accessible. To test this hypothesis, we collected urine from hospitalized patients with community-acquired pneumonia (CAP) and performed a comprehensive screen for urinary tract microbiota signatures, metabolite, and cytokine profiles. CAP patients were diagnosed with influenza or bacterial (S. aureusandS. pneumoniae) etiologies and compared with healthy volunteers. Microbiome signatures showed marked shifts in taxonomic levels in patients with bacterial etiology versus influenza and CAP versus normal. Predictive modeling of 291 microbial and metabolite values achieved a +90% accuracy with LASSO in predicting specific pneumonia etiology. This study demonstrates that urine from patients hospitalized with pneumonia may serve as a reliable and accessible sample to evaluate biomarkers that may diagnose etiology and predict clinical outcomes.

Author Summary

Urine has been classically considered sterile since most microorganisms are not readily culturable under healthy circumstances. Further, many pneumonia patients are immediately placed on antibiotics rendering culture-based techniques useless. However, the advent of next generation sequencing has enabled unprecedented analysis of the microbial communities – living or detected as free DNA – found in many niches of the human body. Here, we describe a urine microbiome as well as metabolites and cytokines measured in patients newly admitted to the hospital diagnosed with influenza or bacterial (S. aureusandS. pneumoniae) infection pneumonia, compared with healthy controls. Using these parameters alone, we were able to achieve high success in predicting patient pneumonia. This study provides a proof of concept that urine samples, which are easily accessible in outpatient and inpatient settings, could provide additional diagnostic insights to patient infectious status and future risk factor for complication.
Neurons in the ventral striatopallidal complex modulate lateral hypothalamic orexin/hypocretin neuron activity: Implications for reward-seeking
Authors: Mitchell Caitlin S. , Mohammadkhani Aida , Manning Elizabeth E. , Campbell Erin J. , Fisher Simon D , Yeoh Jiann W. , Pearl Amy J. , Burton Nicholas J. , Qiao Min , Iredale Jacqueline A. , Bains Jaideep S. , McNally Gavan P. , Andrews Zane A. , Graham Brett A. , Scammell Thomas E. , Lowell Bradford B. , Kong Dong , Borgland Stephanie L. , Dayas Christopher V.
Published: March 2020

Reward-seeking involves the engagement and computation of multiple physiological and motivational parameters. The lateral hypothalamus (LH) is a necessary node in the circuits that control food-seeking and motivation. One group of cells that plays an important yet incompletely understood role in these processes are the orexin/hypocretin (OX/HT) neurons. OX/HT cells are located exclusively within the LH and are implicated in feeding, arousal, and reward-seeking behavior. Importantly, the role of OX/HT neurons in consummatory versus reward-seeking actions is not fully defined, nor are the circuits that control the activity of these neurons under different behavioral states. Here we show that OX/HT neurons respond in real time to food presentation and that this response is modulated by differences in metabolic state. We observed increased OX/HT neuron activity on approach to food, but this activity trended towards pre-approach levels by the start of the consummatory phase. Next, we studied ventrostriatopallidal (VSP) inputs to the OX/HT neurons. Using optogenetics and cell type-specific electrophysiology, we found that ventral pallidum inputs onto OX/HT neurons exert strong inhibitory (and weak excitatory) effects whereas the lateral nucleus accumbens shell provides weaker direct inhibitory connections with OX/HT neurons. These findings reveal that the activity of OX/HT neurons is strongly modulated by metabolic and hedonic state. Further, OX/HT neurons is primarily associated with food approach and that the effect of VSP-terminal output is to suppress OX/HT activity.
A high-resolution map of bacteriophage øX174 transcription
Authors: Logel Dominic Y. , Jaschke Paul R.
Published: March 2020

Bacteriophage øX174 is a model virus for studies across the fields of structural biology, genetics, gut microbiome, and synthetic biology, but did not have a high-resolution transcriptome until this work. In this study we used next-generation sequencing to measure the RNA produced from øX174 while infecting its hostE. coli C.We broadly confirm the past transcriptome model while revealing several interesting deviations from previous knowledge. Additionally, we measure the strength of canonical øX174 promoters and terminators and discover both a putative new promoter that may be activated by heat shock sigma factors, as well as rediscover a controversial Rho-dependent terminator. We also provide evidence for the first antisense transcription observed in theMicroviridaefamily, identify two promoters that may be involved in generating this transcriptional activity, and discuss possible reasons why this RNA may be produced.
The mRNA cap 2’O methyltransferase CMTR1 regulates the expression of certain interferon-stimulated genes
Authors: Williams Graham D. , Gokhale Nandan S. , Snider Daltry L. , Horner Stacy M.
Published: March 2020

Type I interferons (IFN) initiate an antiviral state through a signal transduction cascade that leads to the induction of hundreds of IFN-stimulated genes (ISGs) to restrict viral infection. Recently, RNA modifications on both host and viral RNAs have been described as regulators of infection. However, the impact of host mRNA cap modifications on the IFN response and how this regulates viral infection is unknown. Here, we reveal that CMTR1, an ISG that catalyzes 2’O methylation of the first transcribed nucleotide in cellular mRNA (Cap 1), promotes the protein expression of specific ISGs that contribute to the antiviral response. Depletion of CMTR1 reduces the IFN-induced protein levels of ISG15, MX1, and IFITM1, without affecting their transcript abundance. However, CMTR1 depletion does not significantly affect the IFN-induced protein or transcript abundance of IFIT1 and IFIT3. Importantly, knockdown of IFIT1, which acts with IFIT3 to inhibit the translation of RNAs lacking Cap 1 2’O methylation, restores protein expression of ISG15, MX1, and IFITM1 in cells depleted of CMTR1. Finally, we found that CMTR1 plays a role in restricting RNA virus replication, likely by ensuring the expression of specific antiviral ISGs. Taken together, these data reveal that CMTR1 is required to establish an antiviral state by ensuring the protein expression of a subset of ISGs during the type I IFN response.

Importance

Induction of an efficient type I IFN response is important to control viral infection. We show that the host 2’O methyltransferase CMTR1 facilitates the protein expression of ISGs in human cells by preventing IFIT1 from inhibiting the translation of these mRNAs lacking cap 2’O methylation. Thus, CMTR1 promotes the IFN-mediated antiviral response.
Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes
Authors: Seyres Denis , Cabassi Alessandra , Lambourne John J , Burden Frances , Farrow Samantha , McKinney Harriet , Batista Joana , Kempster Carly , Pietzner Maik , Slingsby Oliver , Cao Thong Huy , Quinn Paulene A , Stefanucci Luca , Sims Matthew C , Rehnstrom Karola , Adams Claire L , Frary Amy , Ergüener Bekir , Kreuzhuber Roman , Mocciaro Gabriele , D’Amore Simona , Koulman Albert , Grassi Luigi , Griffin Julian L , Ng Leong Loke , Park Adrian , Savage David B , Langenberg Claudia , Bock Christoph , Downes Kate , Wareham Nicholas J , Allison Michael , Vacca Michele , Kirk Paul DW , Frontini Mattia
Published: March 2020

Improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis are ongoing healthcare challenges. Using plasma biomarkers analysis coupled with the transcriptional and epigenetic characterisation of cell types involved in thrombosis, obtained from two extreme phenotype groups (obese and lipodystrophy) and comparing these to lean individuals and blood donors, the present study identifies the molecular mechanisms at play, highlighting patterns of abnormal activation in innate immune phagocytic cells and shows that extreme phenotype groups could be distinguished from lean individuals, and from each other, across all data layers. The characterisation of the same obese group, six months after bariatric surgery shows the loss of the patterns of abnormal activation of innate immune cells previously observed. However, rather than reverting to the gene expression landscape of lean individuals, this occurs via the establishment of novel gene expression landscapes. Netosis and its control mechanisms emerge amongst the pathways that show an improvement after surgical intervention. Taken together, by integrating across data layers, the observed molecular and metabolic differences form a disease signature that is able to discriminate, amongst the blood donors, those individuals with a higher likelihood of having cardiometabolic syndrome, even when not presenting with the classic features.
Platelet counts predict prognosis in IPF, but are not the main source of pulmonary TGFβ1
Authors: Chong Deborah. L. W. , Mikolasch Theresia A. , Sahota Jagdeep , Rebeyrol Carine , Garthwaite Helen S. , Booth Helen L. , Heightman Melissa , José Ricardo J. , Khawaja Akif A. , Labelle Myriam , Scotton Christopher J. , Porter Joanna C.
Published: March 2020

Transforming growth factor-β1 (TGFβ1) is the key pro-fibrotic cytokine implicated in the interstitial lung diseases (ILD), including idiopathic pulmonary fibrosis (IPF), but the primary source of TGFβ1 in these diseases is unknown. Platelets have abundant TGFβ1 stores, however their role in IPF is ill-defined. We sought to investigate whether platelets or platelet-derived TGFβ1 mediate IPF disease progression.

ILD/IPF and non-ILD patients were recruited to determine platelet reactivity and followed for mortality. To study whether platelet-derived TGFβ1 modulates pulmonary fibrosis, mice with a targeted deletion of TGFβ1 in megakaryocytes and platelets (TGFβ1fl/fl.PF4-Cre) were used in the bleomycin-induced PF model.

We found a significantly higher mortality in IPF patients with elevated platelet counts, along with significantly increased platelets, neutrophils, TGFβ1 and CCL5 in the lung and bronchoalveolar lavage (BAL) of ILD patients. Despite platelets being readily detected within the lungs of bleomycin-treated mice, neither the degree of pulmonary inflammation or fibrosis were significantly different between TGFβ1fl/fl.PF4-Cre and control mice.

Our results demonstrate for the first-time that platelet-derived TGFβ1 is redundant in driving pulmonary fibrosis in an animal model. However, platelets can predict mortality in IPF implicating other platelet-derived mediators, such as CCL5, in promoting human IPF disease.
Technology usage for teaching and learning law in open and distance learning: a Sri Lankan perspective
Authors: Selvaras Janaka
Published: March 2020

Purpose

The Open University of Sri Lanka (OUSL) is the only institution to deliver legal education through Open and Distance Learning (ODL) in Sri Lanka. This study aims to analyze technology usage in learning and teaching law in the ODL under OUSL to evaluate the accessibility and also challenges.

Design/methodology/approach

A combination of qualitative and quantitative methodologies has been used for the study. This includes both interviews with teachers and surveying among students on the usage of technology in learning and teaching law at OUSL. Since the LL.B Degree Programme of OUSL delivered at six regional centres in Sri Lanka, this study also includes the comparative analysis of technology usage in teaching and learning at selected regional centres.

Findings

The findings indicate that the majority of students have access to technology through mobile phones and are aware of blended learning. Even though they prefer to integrate blended learning with learning law, they do not prefer learning entirely online. Social media and mobile applications are the most preferred modes of blended learning by students. It is also acknowledged that the internal staff has knowledge and access to the use of technology in teaching law while the external staff faces challenges and is in need of adequate training.

Originality/value

The original contribution of this article provides insightful guidelines not only to the OUSL of Sri Lanka but also to the institutions offering similar disciplines through ODL to understand lecturers, learners in the future integration of technology.
Digital engagement strategies and tactics in social media marketing
Authors: Drummond Conor , O'Toole Thomas , McGrath Helen
Published: March 2020

Purpose

Digitalisation has increased the importance of online forms of marketing, including social media (SM) marketing, for entrepreneurial firms. This paper aims to identify digital engagement strategies and tactics in developing SM marketing capability.

Design/methodology/approach

The study uses ethnographic content analysis of an entrepreneurial firm and a network of business-to-business (B2B) actors to classify 1,248 B2B Facebook posts and Twitter tweets from a case of an artisan food producer in addition to semi-structured interviews with 26 networked actors.

Findings

The authors derive a range of digital engagement strategies (8 in total) and tactics (15 in total) for the four defining layers of SM marketing capability, namely, connect, engage, co-ordinate and collaborate.

Research limitations/implications

This research focuses on a case study and a network of B2B actors within the artisan food sector. However, the strategies and tactics are applicable to other entrepreneurial firms and contexts.

Practical implications

The digital engagement strategies and tactics are of direct practical benefit to entrepreneurial firms willing to learn and develop SM marketing capability in interaction with their B2B partners.

Originality/value

This study investigates three under-researched areas, SM as it relates to B2B relationships, and entrepreneurship, and marketing capability gaps in an era of rapid digitalisation. The definition of SM marketing capability and associated digital engagement strategies and tactics are new to the extant literature moving forward the understanding of SM B2B marketing in theory and practice.
A new male entrepreneur?
Authors: Jernberg Frida , Lindbäck Anna , Roos Annie
Published: March 2020

Purpose

The purpose of this study is to investigate whether the representation of male entrepreneurs in the media has changed in the after-effects of the #metoo movement.

Design/methodology/approach

The authors perform a discourse analysis and visual analysis of how male entrepreneurs in the Swedish business magazine Affärsvärlden are represented. A centre-margin analysis is laid out, focusing on who and what constitutes (or endeavours to constitute) the legitimate male entrepreneur.

Findings

The results of the analysis show that male entrepreneurs are represented with different discursive success factors. These success factors are linked to a driven personality, a high-status leisure activity, a supportive but invisible family, a focus on financial measures and a global outlook. Marginally, there has been a change towards more humbleness, and a shift from financial growth to turnover, in the representation of entrepreneurial masculinities after the #metoo movement.

Research limitations/implications

To bring about a more equal norm regarding male entrepreneurial identity, more space and attention must be given in the media to the subordinate masculinities of entrepreneurs.

Originality/value

Previous gender research on entrepreneurship has, to a large extent, focussed on female entrepreneurs and research focussed on male entrepreneurs is conspicuous in its absence. However, the male entrepreneur, just like the female entrepreneur, needs to relate to, be compared with and adapt to a norm of how the ideal entrepreneur should be. Therefore, it is important to establish and illuminate who the male entrepreneur is assumed to be, to better understand and question that role.
Ambiguous hybridity? Main features of China's service-oriented government reform
Authors: Tian Xiaolong , Christensen Tom
Published: March 2020

Purpose

Compared with the worldwide reform trend of transcending new public management (NPM) during the past two decades, China's service-oriented government (SOG) reforms are a relatively different reform approach. After building an SOG was politically identified in 2004, China launched three rounds of SOG reforms in 2008, 2013 and 2018. The purpose of this article is to examine what is meant by China's SOG approach and analyze the reasons behind its emergence. In particular, it explores how this approach might be interpreted in NPM, and particularly post-NPM terms.

Design/methodology/approach

The main theoretical basis of the paper is three theoretical perspectives from organizational theory – the instrumental, cultural and myth perspectives, but more specifically, the concepts complexity and hybridity. The empirical examples are selected from the SOG reforms of 2008, 2013 and 2018. The data used are a combination of public documents and scholarly secondary literature.

Findings

This paper discusses the SOG approach in China as a response to the negative effects of NPM-related reforms and informed by the western post-NPM reforms. It contends that China's SOG is a complex and hybrid approach in which NPM and post-NPM elements coexist and their balance is different from the west.

Originality/value

Few authors have considered China's SOG approach in NPM and post-NPM terms. This paper contributes not only to a wider understanding of the ongoing SOG reform process in China, but also to the understanding of the relevance of public administration theories in a comparative perspective.
Designing an architecture description language for nontechnical actors and purposes (NOTE-ADL)
Authors: Strohmeier Stefan , Gross Felix
Published: March 2020

Purpose

The paper proposes the development of a graphical architecture description language (ADL) that allows a better understanding of software architectures for nontechnical actors and purposes and, beyond, can serve as a communication tool between domain experts and IT experts, for instance, in a software development process.

Design/methodology/approach

The paper follows the methods and guidelines of design science research. By deriving characteristics and general requirements for ADLs from a research literature review and from industry standards, the paper provides a conceptual modeling approach for an ADL. The model design is based on typical requirements and suggestions derived from literature and related work. The application possibilities and advantages are then demonstrated with a usage scenario.

Findings

The paper elaborates a user-oriented ADL that makes software architecture comprehensible for stakeholders and end users. It provides a high level of abstraction and, thus, is not restricted to a particular domain. The paper also provides a corresponding modeling editor as well as an underlying catalogue with symbols and rules for the ADL.

Research limitations/implications

As this is a conceptual study, the ADL has not been practically evaluated yet. Thus, the usefulness of this academic approach for the industry remains to be validated.

Originality/value

The elaborated ADL can serve as a language to visualize software architectures, particularly in the business domain, in a comprehensible manner. Still, it retains the structured character of ADLs to facilitate communication on an IT-near level. In including nontechnical actors, the approach broadens the overall application capabilities of ADLs.