bluuebunny/crossref_metadata_2025 huggingface dataset:
FeS-cluster coordination of vertebrate thioredoxin regulates suppression of hypoxia-induced factor 2α through iron regulatory protein 1
Authors: Berndt Carsten , Hanschmann Eva-Maria , Jordt Laura Magdalena , Gellert Manuela , Thewes Leonie , Ortegón Salas Clara , Poschmann Gereon , Müller Christina Sophia , Bodnar Yana , Schipper Susanne , Handorf Oliver , Nowack Ricardo , Moulis Jean-Marc , Schulzke Carola , Schünemann Volker , Lillig Christopher Horst
Published: August 2020

Iron-regulatory protein 1 (IRP1), a central regulator of iron metabolism in vertebrates, also affects cellular response to hypoxia. IRP1 binds to the iron-responsive element (IRE) in the mRNA encoding hypoxia-inducible factor (HIF) 2α, thereby blocking the translation of the HIF2α-mRNA, and allowing the transcriptional regulation of, e.g., erythropoiesis. Here, we characterize the oxidoreductase thioredoxin 1 (Trx1) as a new regulator of hypoxia signaling. Human and murine Trx1 complex iron-sulfur clusters using one of the active site cysteinyl residues and a vertebrate-specific additional cysteinyl residue outside the active site. FeS-Trx1 is inactive, activated apo-Trx1 reduces cysteinyl residues in the binding pocket of IRP1/apo-Aconitase 1, which allows IRP1 to bind IREs in regulated mRNAs. Therefore, translation of the HIF2α mRNA requires either sufficient iron supply or the lack of reducing power of the Trx system under iron-limiting conditions. FeS-Trx1 thus links both redox and iron homeostasis to hypoxia responses.
Combined deletion of free fatty-acid receptors 1 and 4 minimally impacts glucose homeostasis in mice
Authors: Croze Marine L. , Guillaume Arthur , Ethier Mélanie , Fergusson Grace , Tremblay Caroline , Campbell Scott A. , Maachi Hasna , Ghislain Julien , Poitout Vincent
Published: August 2020

The free fatty-acid receptors FFAR1 (GPR40) and FFAR4 (GPR120) are implicated in the regulation of insulin secretion and insulin sensitivity, respectively. Although GPR120 and GPR40 share similar ligands, few studies have addressed possible interactions between these two receptors in the control of glucose homeostasis. Here we generated mice deficient ingpr120(Gpr120KO) orgpr40(Gpr40KO), alone or in combination (Gpr120/40KO), and metabolically phenotyped male and female mice fed a normal chow or high-fat diet. We assessed insulin secretion in isolated mouse islets exposed to selective GPR120 and GPR40 agonists singly or in combination. Following normal chow feeding, body weight and energy intake were unaffected by deletion of either receptor, although fat mass increased in Gpr120KO females. Fasting blood glucose levels were mildly increased in Gpr120/40KO mice, and in a sex-dependent manner in Gpr120KO and Gpr40KO animals. Oral glucose tolerance was slightly reduced in male Gpr120/40KO mice and in Gpr120KO females, whereas insulin secretion and insulin sensitivity were unaffected. In hyperglycemic clamps, the glucose infusion rate was lower in male Gpr120/40KO mice but insulin and c-peptide levels were unaffected. No changes in glucose tolerance were observed in either single or double KO animals under high-fat feeding. In isolated islets from wild-type mice, the combination of selective GPR120 and GPR40 agonists additively increased insulin secretion. We conclude that while simultaneous activation of GPR120 and GPR40 enhances insulin secretion ex vivo, combined deletion of these two receptors only minimally affects glucose homeostasis in vivo in mice.
High-contrast multifocus microscopy with a single camera and z-splitter prism
Authors: Xiao Sheng , Gritton Howard , Tseng Hua-an , Zemel Dana , Han Xue , Mertz Jerome
Published: August 2020

We present a multifocus imaging strategy based on the use of a simple z-splitter prism that can be assembled from off-the-shelf components. Our technique enables a widefield image stack to be distributed onto a single camera and recorded simultaneously. We exploit the volumetric nature of our image acquisition by further introducing a novel extended-volume 3D deconvolution strategy to suppress far-out-of-focus fluorescence background to significantly improve the contrast of our recorded images, conferring to our system a capacity for quasi optical sectioning. By swapping in different z-splitter configurations, we can prioritize high speed or large 3D field-of-view imaging depending on the application of interest. Moreover, our system can be readily applied to a variety of imaging modalities in addition to fluorescence, such as phase-contrast and darkfield imaging. Because of its simplicity, versatility, and performance, we believe our system will be a useful tool for general biological or biomedical imaging applications.
An image based approach for predicting the effects of endocrine disrupting chemicals on human health using deep learning
Authors: Karatzas Pantelis , Kiouvrekis Yiannis , Stefaneas Petros , Sarimveis Haralambos
Published: August 2020

In recent years, deep neural networks, especially those exhibiting synergistic properties, have been at the cutting edge of image processing, producing very good results. So far, they have been able to successfully address issues of classification and recognition of objects depicted on images. In this paper, a novel idea is presented, where images of chemical structures are used as input information in deep learning neural network architectures aiming at the generation of Quantitative Structure Activity Relationship (QSAR) models, i.e. models that predict properties, activities or adverse effects of chemicals. The proposed method was applied to a case study of particular interest, which is the prediction of endocrine disrupting potential of chemicals. Two different deep learning architectures were applied. The produced ImageNet model proved successful, in terms of accuracy, performance and robustness on training and validation sets. The new approach is proposed to the community as an alternative or complementary method to current practices in QSAR modelling, which can automate and improve the creation of predictive models.
Paediatric Attendances and Acuity in the Emergency Department during the COVID-19 Pandemic
Authors: Rose Katy , Van-Zyl Kerry , Cotton Rachel , Wallace Susan , Cleugh Francesca
Published: August 2020

Aim

To investigate the difference in both numbers and acuity of presentations to the Paediatric Emergency Department (PED) during the peak time period of the current global SARS-CoV-2 pandemic.

Design

This single centre retrospective observational study used routinely collected electronic health data to compare patient presentation characteristics between 21st March and 26th April 2020 compared to the equivalent time period in 2019.

Results

There was a 90% decrease in attendances to PED, with a 10.23% reduction re-attendance rate. Children presenting were younger during the pandemic, with a median age difference of 2 years. They were more likely to present in an ambulance (9.63%), be admitted to hospital (5.75%) and be assigned the highest two Manchester triage categories (6.26%). There was a non-significant trend towards longer lengths of stay. The top 10 presenting complaints remained constant (although the order changed) between time periods. There was no difference in mortality or admission to PICU.

Implications

Our data demonstrates that there has been a significant decrease in numbers of children seeking emergency department care. It suggests that presenting patients were proportionally sicker during the pandemic; however, we would argue that this is more in keeping with appropriate acuity for PED presentations, as there were no differences in PICU admission rate or mortality. We explore some of the possible reasons behind the decrease in presentations and the implications for service planning ahead of the winter months.
Rapid systematic review of the sensitivity of SARS-CoV-2 molecular testing on saliva compared to nasopharyngeal swabs
Authors: Peeters E. , Singh S. Kaur Dhillon Ajit , Vandesompele J. , Mestdagh P. , Hutse V. , Arbyn M.
Published: August 2020

Background

Nasopharyngeal sampling has been the standard collection method for COVID-19 testing. Due to its invasive nature and risk of contamination for health care workers who collect the sample, non-invasive and safe sampling methods like saliva, can be used alternatively.

Methods

A rapid systematic search was performed in PubMed and medRxiv, with the last retrieval on June 6th, 2020. Studies were included if they compared saliva with nasopharyngeal sampling for the detection of SARS-CoV-2 RNA using the same RT-qPCR applied on both types of samples. The primary outcome of interest was the relative sensitivity of SARS-CoV-2 testing on saliva versus nasopharyngeal samples (used as the comparator test). A secondary outcome was the proportion of nasopharyngeal-positive patients that tested also positive on a saliva sample.

Results

Eight studies were included comprising 1070 saliva-nasopharyngeal sample pairs allowing assessment of the first outcome. The relative sensitivity of SARS-CoV-2 testing on saliva versus nasopharyngeal samples was 0.97 (95% CI=0.92-1.02). The second outcome incorporated patient data (n=257) from four other studies (n=97 patients) pooled with four studies from the first outcome (n=160 patients). This resulted in a pooled proportion of nasopharyngeal positive cases that was also positive on saliva of 86% (95% CI=77-93%).

Discussion

Saliva could potentially be considered as an alternative sampling method when compared to nasopharyngeal swabs. However, studies included in this review often were small and involved inclusion of subjects with insufficient information on clinical covariates. Most studies included patients who were symptomatic (78%, 911/1167). Therefore, additional and larger studies should be performed to verify the relative performance of saliva in the context of screening of asymptomatic populations and contact-tracing.
Features and Functions of Systemic and Mucosal Humoral Immunity Among SARS-CoV-2 Convalescent Individuals
Authors: Butler Savannah E. , Crowley Andrew R. , Natarajan Harini , Xu Shiwei , Weiner Joshua A. , Lee Jiwon , Wieland-Alter Wendy , Connor Ruth I. , Wright Peter F. , Ackerman Margaret E.
Published: August 2020

Understanding humoral immune responses to SARS-CoV-2 infection will play a critical role in the development of vaccines and antibody-based interventions. We report systemic and mucosal antibody responses in convalescent individuals who experienced varying disease severity. Robust antibody responses to diverse SARS-CoV-2 antigens and evidence of elevated responses to endemic CoV were observed among convalescent donors. SARS-CoV-2-specific IgA and IgG responses were often negatively correlated, particularly in mucosal samples, suggesting subject-intrinsic biases in isotype switching. Assessment of antibody-mediated effector functions revealed an inverse correlation between systemic and mucosal neutralization activity and site-dependent differences in the isotype of neutralizing antibodies. Serum neutralization correlated with systemic anti-SARS-CoV-2 IgG and IgM response magnitude, while mucosal neutralization was associated with nasal SARS-CoV-2-specific IgA. These findings begin to map how diverse Ab characteristics relate to Ab functions and outcomes of infection, informing public health assessment strategies and vaccine development efforts.
An examination of school reopening strategies during the SARS-CoV-2 pandemic
Authors: Landeros Alfonso , Ji Xiang , Lange Kenneth , Stutz Timothy C. , Xu Jason , Sehl Mary E. , Sinsheimer Janet S.
Published: August 2020

The SARS-CoV-2 pandemic led to closure of nearly all K-12 schools in the United States of America in March 2020. Although reopening K-12 schools for in-person schooling is desirable for many reasons, officials understand that risk reduction strategies and detection of cases are imperative in creating a safe return to school. Furthermore, consequences of reclosing recently opened schools are substantial and impact teachers, parents, and ultimately educational experiences in children. To address competing interests in meeting educational needs with public safety, we compare the impact of physical separation through school cohorts on SARS-CoV-2 infections against policies acting at the level of individual contacts within classrooms. Using an age-stratified Susceptible-Exposed-Infected-Removed model, we explore influences of reduced class density, transmission mitigation, and viral detection on cumulative prevalence. We consider several scenarios over a 6-month period including (1) multiple rotating cohorts in which students cycle through in-person instruction on a weekly basis, (2) parallel cohorts with in-person and remote learning tracks, (3) the impact of a hypothetical testing program with ideal and imperfect detection, and (4) varying levels of aggregate transmission reduction. Our mathematical model predicts that reducing the number of contacts through cohorts produces a larger effect than diminishing transmission rates per contact. Specifically, the latter approach requires dramatic reduction in transmission rates in order to achieve a comparable effect in minimizing infections over time. Further, our model indicates that surveillance programs using less sensitive tests may be adequate in monitoring infections within a school community by both keeping infections low and allowing for a longer period of instruction. Lastly, we underscore the importance of factoring infection prevalence in deciding when a local outbreak of infection is serious enough to require reverting to remote learning.
Precise genome engineering inDrosophilausing prime editing
Authors: Bosch Justin A. , Birchak Gabriel , Perrimon Norbert
Published: August 2020

Precise genome editing is a valuable tool to study gene function in model organisms. Prime editing, a precise editing system developed in mammalian cells, does not require double strand breaks or donor DNA and has low off-target effects. Here, we applied prime editing for the model organismDrosophila melanogasterand developed conditions for optimal editing. By expressing prime editing components in cultured cells or somatic cells of transgenic flies, we precisely installed premature stop codons in three classical visible marker genes,ebony,white, andforked. Furthermore, by restricting editing to germ cells, we demonstrate efficient germ line transmission of a precise edit inebonyto ~50% of progeny. Our results suggest that prime editing is a useful system inDrosophilato study gene function, such as engineering precise point mutations, deletions, or epitope tags.
A novel prokaryotic CRISPR-Cas12a based tool for programmable transcriptional activation and repression
Authors: Schilling Christoph , Koffas Mattheos A.G. , Sieber Volker , Schmid Jochen
Published: August 2020

Transcriptional perturbation using inactivated CRISPR-nucleases (dCas) is a common method in eukaryotic organisms. While rare examples of dCas9 based tools for prokaryotes have been described, multiplexing approaches are limited due to the used effector nuclease. For the first time, a dCas12a derived tool for the targeted activation and repression of genes was developed. Therefore, a previously described SoxS activator domain was linked to dCas12a to enable programmable activation of gene expression. Proof of principle of transcriptional regulation was demonstrated based on fluorescence reporter assays using the alternative host organismPaenibacillus polymyxaas well asEscherichia coli. Single target and multiplex CRISPR interference targeting the exopolysaccharide biosynthesis ofP. polymyxawas shown to emulate polymer compositions of gene knock-outs. Simultaneous expression of 11 gRNAs targeting multiple lactate dehydrogenases and a butanediol dehydrogenase resulted in decreased lactate formation, as well as an increased butanediol production in microaerobic fermentation processes. Even though Cas12a is more restricted in terms of its genomic target sequences compared to Cas9, its ability to efficiently process its own guide RNAsin vivomakes it a promising tool to orchestrate sophisticated genetic reprogramming of bacterial cells or to screen for engineering targets in the genome. The developed tool will accelerate metabolic engineering efforts in the alternative host organismP. polymyxaand might be also applied for other bacterial cell factories.
Orphan CpG islands boost the regulatory activity of poised enhancers and dictate the responsiveness of their target genes
Authors: Pachano Tomás , Sánchez-Gaya Víctor , Mariner-Faulí María , Ealo Thais , Asenjo Helena G. , Respuela Patricia , Cruz-Molina Sara , van Ijcken Wilfred F. J. , Landeira David , Rada-Iglesias Álvaro
Published: August 2020

ARTICLE

CpG islands (CGIs) represent a distinctive and widespread genetic feature of vertebrate genomes, being associated with ∼70% of all annotated gene promoters1. CGIs have been proposed to control transcription initiation by conferring nearby promoters with unique chromatin properties2–4. In addition, there are thousands of distal or orphan CGIs (oCGIs) whose functional relevance and mechanism of action are barely known5–7. Here we show that oCGIs are an essential component of poised enhancers (PEs)8, 9that boost their long-range regulatory activity and dictate the responsiveness of their target genes. Using a CRISPR/Cas9 knock-in strategy in mESC, we introduced PEs with or without oCGIs within topological associating domains (TADs) harbouring genes with different types of promoters. By evaluating the chromatin, topological and regulatory properties of the engineered PEs, we uncover that, rather than increasing their local activation, oCGIs boost the physical and functional communication between PEs and distally located developmental genes. Furthermore, we demonstrate that developmental genes with CpG rich promoters are particularly responsive to PEs and that such responsiveness depends on the presence of oCGIs. Therefore, our work unveils a novel role for CGIs as genetic determinants of the compatibility between genes and enhancers, thus providing major insights into how developmental gene expression programs are deployed under both physiological and pathological conditions10–12.
Automatic inference of demographic parameters using Generative Adversarial Networks
Authors: Wang Zhanpeng , Wang Jiaping , Kourakos Michael , Hoang Nhung , Lee Hyong Hark , Mathieson Iain , Mathieson Sara
Published: August 2020

Abstract

Population genetics relies heavily on simulated data for validation, inference, and intuition. In particular, since the evolutionary “ground truth” for real data is always limited, simulated data is crucial for training supervised machine learning methods. Simulation software can accurately model evolutionary processes, but requires many hand-selected input parameters. As a result, simulated data often fails to mirror the properties of real genetic data, which limits the scope of methods that rely on it. Here, we develop a novel approach to estimating parameters in population genetic models that automatically adapts to data from any population. Our method,pg-gan, is based on a generative adversarial network that gradually learns to generate realistic synthetic data. We demonstrate that our method is able to recover input parameters in a simulated isolation-with-migration model. We then apply our method to human data from the 1000 Genomes Project, and show that we can accurately recapitulate the features of real data.
CODEX, a neural network approach to explore signaling dynamics landscapes
Authors: Jacques Marc-Antoine , Dobrzyński Maciej , Gagliardi Paolo Armando , Sznitman Raphael , Pertz Olivier
Published: August 2020

Fluorescent biosensors routinely yield thousands of single-cell, heterogeneous, multi-dimensional signaling trajectories that are difficult to mine for relevant information. We present CODEX, an approach based on artificial neural networks to guide exploration of time-series datasets and to identify motifs in dynamic signaling states.
PD-1 blockade exacerbatesMycobacterium tuberculosisinfection in rhesus macaques
Authors: Kauffman Keith D , Sakai Shunsuke , Lora Nickiana E , Namasivayam Sivaranjani , Baker Paul J , Kamenyeva Olena , Foreman Taylor W , Nelson Christine E , Oliveira-de-Souza Deivide , Vinhaes Caian L. , Yaniv Ziv , Lindestam Arleham Cecilia S , Sette Alessandro , Freeman Gordon J , Moore Rashida ,   the NIAID/DIR Tuberculosis Imaging Program, Sher Alan , Mayer-Barber Katrin D , Andrade Bruno B , Kabat Juraj , Via Laura E , Barber Daniel L
Published: August 2020

Boosting immune cell function by targeting the co-inhibitory receptor PD-1 may have applications in the treatment of chronic infections. Here we examine the role of PD-1 duringMycobacterium tuberculosis(Mtb) infection of rhesus macaques. Animals treated with αPD-1 mAb developed worse disease and higher granuloma bacterial loads compared to isotype control treated monkeys. PD-1 blockade increased the number and functionality of granuloma Mtb-specific CD8 T cells. In contrast, Mtb-specific CD4 T cells in αPD-1 treated macaques were not increased in number or function in granulomas, upregulated high levels of CTLA-4 and exhibited reduced intralesional trafficking in live imaging studies. In granulomas of αPD-1 treated animals, multiple pro-inflammatory cytokines were elevated, and more cytokines correlated with bacterial loads, leading to the identification of a role for caspase 1 in the exacerbation of tuberculosis after PD-1 blockade. Lastly, increased Mtb bacterial loads after PD-1 blockade were found to associate with the composition of the intestinal microbiota prior to infection in individual macaques. Therefore, PD-1-mediated co-inhibition is required for control of Mtb infection in macaques, perhaps due to its role in dampening detrimental inflammation as well as allowing for normal CD4 T cell responses.
Age-independent influence of hematopoietic stem and progenitor cell populations during hematopoietic reconstitution
Authors: Gotzhein Frauke , Aranyossy Tim , Thielecke Lars , Sonntag Tanja , Thaden Vanessa , Fehse Boris , Müller Ingo , Glauche Ingmar , Cornils Kerstin
Published: August 2020

Hematopoietic stem cell transplantation (HSCT) following myeloablative conditioning represents the only curative treatment option to overcome numerous hematologic malignancies. Despite the overall clinical success to achieve reconstitution of the blood system in many patients, the length of the aplastic phase until recovery response remains a critical parameter for patient survival. Fatal infections are the major risk factor for immunocompromised individuals and in many cases lead to transplant related morbidity and mortality. Therefore, we hypothesized that transplants from young donors might be beneficial for the spatiotemporal blood reconstitution in comparison to old grafts. Here we report on our multicolor-coded barcode system (BC32) to track hematopoietic stem and progenitor cell (HSPC) populations in a murine model of HSCT. By using different experimental settings of young and aged donor and recipient animals we compared the influence of age on graft composition, leukocyte recovery and more precisely, the contribution of individual HSPC subpopulations to the process. We show that blood reconstitution is substantially driven and maintained by HSCs and MPPs, while the latter accounted for higher output rates than HSCs, confirmed by FACS and NGS analyses. Reconstitution patterns were highly polyclonal and stable in all animals aside from variability between individual animals. This leads to the conclusion that HSPCs home, engraft and differentiate independently of donor and recipient age in our experimental conditions. Our findings add to ongoing efforts to expand the application of HSCT in older individuals while minimizing therapy related risks resulting from intensive myeloablative conditioning or incomplete blood reconstitution.
The application of drones for mosquito larval habitat identification in rural environments: a practical approach for malaria control?
Authors: Stanton Michelle C , Kalonde Patrick , Zembere Kennedy , Spaans Remy Hoek , Jones Christopher M
Published: August 2020

Spatial and temporal trends in mosquito-borne diseases are driven by the locations and seasonality of larval habitat. One method of disease control is to decrease the mosquito population by removing habitat and/or reduce the likelihood of larvae developing into adults, known as larval source management (LSM). In malaria control, LSM is currently considered impractical in rural areas due to perceived difficulties in identifying target areas. High resolution drone mapping is being considered as a practical solution to address this barrier. In this paper, we use our experiences of drone-led larval habitat identification in Malawi to assess the accuracy and practicalities of this approach.

Drone imagery and larval surveys were conducted in Kasungu district, Malawi between 2018-2020. Water bodies and aquatic vegetation were identified in the imagery using both manual methods and geographical object-based image analysis (GeoOBIA) and the performance of the classifications were compared. Larval sampling sites were characterised by biotic factors visible in drone imagery (e.g. vegetation coverage, type), and generalised linear mixed models were used to determine their association with larval presence.

Imagery covering an area of 8.9km2across eight sites was captured. Characteristics associated with rural larval habitat were successfully identified using GeoOBIA (e.g. median accuracy = 0.98, median kappa = 0.96 using a standard RGB camera), with a median of 18.3% being classed as surface water, compared to 20.1% using manual identification. The GeoOBIA approach, however, required greater processing time and technical skills. Larval samples were captured from 326 sites, and a relationship was identified between larval presence and vegetation (log-OR=1.44, p=0.01). Vegetation type was also a significant factor when considering late stage anopheline larvae only.

Our study demonstrates the potential for drone-acquired imagery as a tool to support the identification of mosquito larval habitat in rural areas where malaria is endemic. There are, however, technical challenges to overcome before it can be smoothly integrated into malaria control activities. Further consultations between experts and stakeholders in the fields of drones, image analysis and vector control are needed to develop more detailed guidance on how this technology can be most effectively exploited.
A MATLAB Toolbox for Modeling Genetic Circuits in Cell-Free Systems
Authors: Singhal Vipul , Tuza Zoltan A. , Sun Zachary Z. , Murray Richard M.
Published: August 2020

We introduce a MATLAB based simulation toolbox, called txtlsim, for anE. colibased Transcription-Translation (TX-TL) system. This toolbox accounts for several cell-free related phenomena, such as resource loading, consumption, and degradation, and in doing so, models the dynamics of TX-TL reactions for the entire duration of batch-mode experiments. We use a Bayesian parameter inference approach to characterize the reaction rate parameters associated with the core transcription, translation and mRNA degradation mechanics of the toolbox, allowing it to reproduce constitutive mRNA and protien expression trajectories. We demonstrate the use of this characterized toolbox in a circuit behavior prediction case study for an incoherent feed-forward loop.
Genomic and chemical diversity ofBacillus subtilissecondary metabolites against plant pathogenic fungi
Authors: Kiesewalter Heiko T. , Lozano-Andrade Carlos N. , Wibowo Mario , Strube Mikael L. , Maróti Gergely , Snyder Dan , Jørgensen Tue Sparholt , Larsen Thomas O. , Cooper Vaughn S. , Weber Tilmann , Kovács Ákos T.
Published: August 2020

Bacillus subtilisproduces a wide range of secondary metabolites providing diverse plant-growth-promoting and biocontrol abilities. These secondary metabolites include non-ribosomal peptides (NRPs) with strong antimicrobial properties, causing either cell lysis, pore formation in fungal membranes, inhibition of certain enzymes, or bacterial protein synthesis. However, the natural products ofB. subtilisare mostly studied either in laboratory strains or in individual isolates and therefore, a comparative overview ofB. subtilissecondary metabolites is missing.

In this study, we have isolated 23B. subtilisstrains from eleven sampling sites, compared the fungal inhibition profiles of wild types and their NRPs mutants, followed the production of targeted lipopeptides, and determined the complete genomes of 13 soil isolates. We discovered that non-ribosomal peptide production varied amongB. subtilisstrains co-isolated from the same soil samples.In vitroantagonism assays revealed that biocontrol properties depend on the targeted plant pathogenic fungus and the testedB. subtilisisolate. While plipastatin alone is sufficient to inhibitFusariumsp., a combination of plipastatin and surfactin is required to hinder the growth ofBotrytis cinerea. Detailed genomic analysis revealed that altered NRP production profiles in certain isolates is due to missing core genes, nonsense mutation, or potentially altered gene regulation.

Our study combines microbiological antagonism assays with chemical NRPs detection and biosynthetic gene cluster predictions in diverseB. subtilissoil isolates to provide a broader overview of the secondary metabolite chemodiversity ofB. subtilis.

IMPORTANCE

Secondary or specialized metabolites with antimicrobial activities define the biocontrol properties of microorganisms. Members of theBacillusgenus produce a plethora of secondary metabolites, of which non-ribosomally produced lipopeptides in particular display strong antifungal activity. To facilitate prediction of the biocontrol potential of newBacillus subtilisisolates, we have explored thein vitroantifungal inhibitory profiles of recentB. subtilisisolates, combined with analytical natural product chemistry, mutational analysis, and detailed genome analysis of biosynthetic gene clusters. Such a comparative analysis helped to explain why selectedB. subtilisisolates lack production of certain secondary metabolites.
Epitomic analysis of the specificity of conformation-dependent, anti-Aß amyloid monoclonal antibodies
Authors: Reyes-Ruiz Jorge Mauricio , Nakajima Rie , Baghallab Ibtisam , Goldschmidt Luki , Sosna Justyna , Mai Ho Phuong Nguyen , Kumosani Taha , Felgner Philip L. , Glabe Charles
Published: August 2020

Antibodies against Aß amyloid are indispensable research tools and potential therapeutics for Alzheimer’s Disease, but display several unusual properties, such as specificity for aggregated forms of the peptide, ability to distinguish polymorphic aggregate structures and ability to recognize generic aggregation-related epitopes formed by unrelated amyloid sequences. Understanding the mechanisms underlying these unusual properties of anti-amyloid antibodies and the structures of their corresponding epitopes is crucial for the understanding why antibodies display different therapeutic activities and for the development of more effective therapeutic agents. Here we employed a novel “epitomic” approach to map the fine structure of the epitopes of 28 monoclonal antibodies against amyloid-beta using immunoselection of random sequences from a phage display library, deep sequencing and pattern analysis to define the critical sequence elements recognized by the antibodies. Although most of the antibodies map to major linear epitopes in the amino terminal 1-14 residues of Aß, the antibodies display differences in the target sequence residues that are critical for binding and in their individual preferences for non-target residues, indicating that the antibodies bind to alternative conformations of the sequence by different mechanisms. Epitomic analysis also identifies more discontinuous, non-overlapping sequence Aß segments than peptide array approaches that may constitute the conformational epitopes that underlie the aggregation specificity of antibodies. Aggregation specific antibodies recognize sequences that display a significantly higher predicted propensity for forming amyloid than antibodies that recognize monomer, indicating that the ability of random sequences to aggregate into amyloid is a critical element of their binding mechanism.
Alveolitis in severe SARS-CoV-2 pneumonia is driven by self-sustaining circuits between infected alveolar macrophages and T cells
Authors: Grant Rogan A. , Morales-Nebreda Luisa , Markov Nikolay S. , Swaminathan Suchitra , Guzman Estefany R. , Abbott Darryl A. , Donnelly Helen K. , Donayre Alvaro , Goldberg Isaac A. , Klug Zasu M. , Borkowski Nicole , Lu Ziyan , Kihshen Hermon , Politanska Yuliya , Sichizya Lango , Kang Mengjia , Shilatifard Ali , Qi Chao , Argento A. Christine , Kruser Jacqueline M. , Malsin Elizabeth S. , Pickens Chiagozie O. , Smith Sean , Walter James M. , Pawlowski Anna E. , Schneider Daniel , Nannapaneni Prasanth , Abdala-Valencia Hiam , Bharat Ankit , Gottardi Cara J. , Budinger GR Scott , Misharin Alexander V. , Singer Benjamin D. , Wunderink Richard G. ,   for The NU SCRIPT Study Investigators
Published: August 2020

Some patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) develop severe pneumonia and the acute respiratory distress syndrome (ARDS) [1]. Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from other types of pneumonia [2]. We collected bronchoalveolar lavage fluid samples from 86 patients with SARS-CoV-2-induced respiratory failure and 252 patients with known or suspected pneumonia from other pathogens and subjected them to flow cytometry and bulk transcriptomic profiling. We performed single cell RNA-Seq in 5 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours of intubation. In the majority of patients with SARS-CoV-2 infection at the onset of mechanical ventilation, the alveolar space is persistently enriched in alveolar macrophages and T cells without neutrophilia. Bulk and single cell transcriptomic profiling suggest SARS-CoV-2 infects alveolar macrophages that respond by recruiting T cells. These T cells release interferon-gamma to induce inflammatory cytokine release from alveolar macrophages and further promote T cell recruitment. Our results suggest SARS-CoV-2 causes a slowly unfolding, spatially-limited alveolitis in which alveolar macrophages harboring SARS-CoV-2 transcripts and T cells form a positive feedback loop that drives progressive alveolar inflammation.

This manuscript is accompanied by an online resource:https://www.nupulmonary.org/covid-19/

One sentence summary

SARS-CoV-2-infected alveolar macrophages form positive feedback loops with T cells in patients with severe COVID-19.
Tracking H3K27me3 and H4K20me1 during XCI reveals similarities in enrichment dynamics
Authors: Tjalsma Sjoerd J. D. , Hori Mayako , Sato Yuko , Bousard Aurelie , Ohi Akito , Raposo Ana Cláudia , Roensch Julia , Le Saux Agnes , Nogami Jumpei , Maehara Kazumitsu , Kujirai Tomoya , Handa Tetsuya , Bagés-Arnal Sandra , Ohkawa Yasuyuki , Kurumizaka Hitoshi , da Rocha Simão Teixeira , Żylicz Jan J. , Kimura Hiroshi , Heard Edith
Published: August 2020

During X chromosome inactivation (XCI), in female placental mammals, gene silencing is initiated by theXistlong-noncoding RNA.Xistaccumulation at the X leads to enrichment of specific chromatin marks, including PRC2-dependent H3K27me3 and SETD8-dependent H4K20me1. However, the dynamics of this process in relation toXistRNA accumulation remains unknown as is the molecular mechanism allowing for H4K20me1 enrichment. To follow XCI dynamics in living cells, we developed a genetically-encoded, H3K27me3-specific intracellular antibody, or H3K27me3-mintbody. By combining it with live-imaging of H4K20me1, the X chromosome andXistRNA we uncover similarities in the initial accumulation dynamics of H3K27me3 and H4K20me1. Further ChIP-seq analysis confirmed concurrent accumulation of both marks during XCI albeit with distinct genomic distributions. Using aXistB and C repeat mutant, which can silence the X but does not allow for H3K27me3 deposition, we also found a lack of H4K20me1 enrichment. Thus, these two marks accumulate at the X thanks to the same region ofXistand H4K20me1 in particular may have a role in the chromatin compaction that characterises facultative heterochromatin.
Lead emissions from the use of leaded avgas in Turkey
Authors: Altuntas Onder
Published: August 2020

Purpose

This study aims to present the impact of using leaded avgas in piston-prop aircraft, in Turkey.

Design/methodology/approach

Increasing air traffic directly increases the total amount of consumed aviation fuels (kerosene or avgas). The number of aircraft and traffic that will increase soon will further increase fuel consumption. For this reason, aircraft power generation methods (long term) must be changed or the fuel must be improved (short term). The avgas used in piston-prop aircraft is known to contain lead and as a result, the production or consumption of avgas has adverse effects on human health, the ecosystem quality and resources.

Findings

The overall human health impact, ecosystem quality impact and resource impact in Turkey were determined to be 2.83 disability-adjusted life years, 1.21 × 10−04 species.yr and $138, respectively. According to the results, although the normalized total effect of Turkey was calculated as 208.18 nkg, 43.89% of the total was observed in the Marmara region.

Originality/value

The originality is the use of real-time values for all calculations. For the purpose of showing the most impacted or damaged regions in Turkey via a life cycle analysis, a new definition, the normalized total effect in nkg, is defined in this study.
Heterogeneous beliefs and idiosyncratic volatility puzzle: evidence from China
Authors: He Mao , Huang Juncheng , Zhu Hongquan
Published: August 2020

Purpose

The purpose of our study is to explore the “idiosyncratic volatility puzzle” in Chinese stock market from the perspective of investors' heterogeneous beliefs. To delve into the relationship between idiosyncratic volatility and investors' heterogeneous beliefs, and uncover the ability of heterogeneous beliefs, as well as to explain the “idiosyncratic volatility puzzle”, we construct our study as follows.

Design/methodology/approach

Our study adopts the unexpected trading volume as proxies of heterogeneity, the residual of Fama–French three-factor model as proxies of idiosyncratic volatility. Portfolio strategies and Fama–MacBeth regression are used to investigate the relationship between the two proxies and stock returns in Chinese A-share market.

Findings

Investors' heterogeneous beliefs, as an intermediary variable, are positively correlated with idiosyncratic volatility. Meanwhile, it could better demonstrate the negative correlation between the idiosyncratic volatility and future stock returns. It is one of the economic mechanisms linking idiosyncratic volatility to subsequent stock returns, which can account for 11.28% of the puzzle.

Originality/value

The findings indicate that idiosyncratic volatility is significantly and positively correlated with heterogeneous beliefs and that heterogeneous beliefs are effective intervening variables to explain the “idiosyncratic volatility puzzle”.
The relationship between environmental degradation, energy use and economic growth in Nigeria: new evidence from non-linear ARDL
Authors: Musibau Hammed Oluwaseyi , Shittu Waliu Olawale , Ogunlana Fatai Olarewaju
Published: August 2020

Purpose

The purpose of this paper is to study the relationship among environmental degradation, energy use and economic growth, thus lending a voice to testing the relevance, or otherwise, of the environmental Kuznets curve (EKC) hypothesis in Nigeria.

Design/methodology/approach

The authors rely on the secondary data obtained from World Bank’s World Development Indicators for Nigeria, between 1981 and 2014. The non-linear autoregressive distributed lag (ARDL) technique is used after examining the unit root properties – using the augmented Dickey–Fuller and Phillips–Perron methods – and the long-run relationship – using the ARDL bounds approach to estimate the asymmetries in the effects of economic growth on the environment.

Findings

The findings of this study uphold the relevance of the EKC hypothesis in Nigeria, as the growth of GDP first reduces the environmental quality but raises it over time. Furthermore, the use of energy is found to deteriorate environmental quality, given that CO2 rises by 0.002% for a unit increase in the consumption of energy in Nigeria.

Research limitations/implications

A limitation to this research is the data coverage, which is just between 1981 and 2014, based on availability. One other limitation is the use of electric power consumption as a proxy for energy use (because of the difficulty in obtaining accurate data on energy consumption in Nigeria). Future research should, therefore, test different other proxies, to either agree with the findings or justify any deviation therefrom. Also, the use of up-to-date data is recommended as an improvement to this study, while a non-linear technique should be used on studies involving the panel of countries.

Originality/value

Many studies have examined this relationship by simply taking the square of GDP as a measure of its non-linear effect on the environment. The authors are one of the first who consider the asymmetric effect of economic growth on the environment through the non-linear ARDL technique. With this, the partial sums of positive and negative changes in economic growth on the environment are easily established.
Corporate social responsibility reporting of local oil companies in Nigeria
Authors: Odera Odhiambo
Published: August 2020

Purpose

The purpose of this paper is to analyze annual reports through content analysis. Corporate social responsibility reporting (CSRR) extent and type are measured by the number of sentences. CSRR are further classified into three subcategories according to whether they are negative, neutral or positive reports and then their proportions compared through descriptive analysis.

Design/methodology/approach

This paper seeks to examine and identify factors influencing CSRR practices of local oil companies (LOCs) in Nigeria. It aims at distinguishing CSRR levels by examining both the quantity and quality of reporting.

Findings

For the extent of CSRR, employee-related information was the most reported category with community reports being of greater quality in the LOCs. The majority of the total CSRR in the LOCs was positive with very little evidence of negative news.

Research limitations/implications

The measurement of CSRR focuses only on annual reports, without consideration of other reporting media, such as standalone reports. CSRR are assumed to be voluntary for the companies, and they may choose not to report any information in annual reports, as there are no regulations or reporting guidelines in Nigeria to be followed.

Originality/value

The main contribution of this study lies in identifying the factors that have led to diversity and uniqueness in CSRR in LOCs. As such, this study seeks to contribute to the development of understanding multiple factors that could give rise to changing patterns of CSRR.
Research on the influence of ground effect on the performance of robotic fish propelled by oscillating paired pectoral fins
Authors: Ma Hongwei , Ren Shuai , Wang Junxiang , Ren Hui , Liu Yang , Bi Shusheng
Published: August 2020

Purpose

This paper aims to carry out the research on the influence of ground effect on the performance of robotic fish propelled by oscillating paired pectoral fins.

Design/methodology/approach

The two-dimensional ground effect model of the oscillating pectoral fin without considering flexible deformation is established by introducing a two-dimensional fluid ground effect model. The parameters of the influence of ground effect on the oscillating pectoral fin are analyzed. Finally, the ground effect test platform is built, and a series of hydrodynamic experiments are carried out to study the influence of ground effect on the propulsion performance of the robotic fish propelled by oscillating paired pectoral fins under different motion parameters.

Findings

The thickness of the trailing edge and effective clearance are two important parameters that can change the influence of ground effect on the rigid pectoral fin. The experimental results are consistent with that obtained through theoretical analysis within a certain extent, which indicates that the developed two-dimensional ground effect model in this paper can be used to analyze the influence of ground effect on the propulsion performance of the oscillating pectoral fin. The experiment results show that the average thrust increases with the decreasing distance between the robot fish and the bottom. Meanwhile, with the increase of oscillation frequency and amplitude, the average thrust increases gradually.

Originality/value

The developed two-dimensional ground effect model provides the theoretical basis for the further research on the influence of ground effect on the propulsion performance of the oscillating pectoral fin. It can also be used in the design of the bionic pectoral fins.
Big data management and environmental performance: role of big data decision-making capabilities and decision-making quality
Authors: Nisar Qasim Ali , Nasir Nadia , Jamshed Samia , Naz Shumaila , Ali Mubashar , Ali Shahzad
Published: August 2020

Purpose

This study is undertaken to examine the antecedents and role of big data decision-making capabilities toward decision-making quality and environmental performance among the Chinese public and private hospitals. It also examined the moderating effect of big data governance that was almost ignored in previous studies.

Design/methodology/approach

The target population consisted of managerial employees (IT experts and executives) in hospitals. Data collected using a survey questionnaire from 752 respondents (374 respondents from public hospitals and 378 respondents from private hospitals) was subjected to PLS-SEM for analysis.

Findings

Findings revealed that data management challenges (leadership focus, talent management, technology and organizational culture for big data) are significant antecedents for big data decision-making capabilities in both public and private hospitals. Moreover, it was also found that big data decision-making capabilities played a key role to improve the decision-making quality (effectiveness and efficiency), which positively contribute toward environmental performance in public and private hospitals of China. Public hospitals are playing greater attention to big data management for the sake of quality decision-making and environmental performance than private hospitals.

Practical implications

This study provides guidelines required by hospitals to strengthen their big data capabilities to improve decision-making quality and environmental performance.

Originality/value

The proposed model provides an insight look at the dynamic capabilities theory in the domain of big data management to tackle the environmental issues in hospitals. The current study is the novel addition in the literature, and it identifies that big data capabilities are envisioned to be a game-changer player in effective decision-making and to improve the environmental performance in health sector.