bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia
Authors: Moutal Aubin , Martin Laurent F. , Boinon Lisa , Gomez Kimberly , Ran Dongzhi , Zhou Yuan , Stratton Harrison J. , Cai Song , Luo Shizhen , Gonzalez Kerry Beth , Perez-Miller Samantha , Patwardhan Amol , Ibrahim Mohab M. , Khanna Rajesh
Published: July 2020

Global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues unabated. Binding of SARS-CoV-2’s Spike protein to host angiotensin converting enzyme 2 triggers viral entry, but other proteins may participate, including neuropilin-1 receptor (NRP-1). As both Spike protein and vascular endothelial growth factor-A (VEGF-A) – a pro-nociceptive and angiogenic factor, bind NRP-1, we tested if Spike could block VEGF-A/NRP-1 signaling. VEGF-A–triggered sensory neuronal firing was blocked by Spike protein and NRP-1 inhibitor EG00229. Pro-nociceptive behaviors of VEGF-A were similarly blocked via suppression of spontaneous spinal synaptic activity and reduction of electrogenic currents in sensory neurons. Remarkably, preventing VEGF-A/NRP-1 signaling was antiallodynic in a neuropathic pain model. A ‘silencing’ of pain via subversion of VEGF-A/NRP-1 signaling may underlie increased disease transmission in asymptomatic individuals.
Interplay of Monocytes and T Lymphocytes in COVID-19 Severity
Authors: Padgett Lindsey E. , Dinh Huy Q. , Chee Serena J. , Olingy Claire E. , Wu Runpei , Araujo Daniel J. , Vijayanand Pandurangan , Ottensmeier Christian H. , Hedrick Catherine C.
Published: July 2020

The COVID-19 pandemic represents an ongoing global crisis that has already impacted over 13 million people. The responses of specific immune cell populations to the disease remain poorly defined, which hinders improvements in treatment and care management. Here, we utilized mass cytometry (CyTOF) to thoroughly phenotype peripheral myeloid cells and T lymphocytes from 30 convalescent patients with mild, moderate, and severe cases of COVID-19. We identified 10 clusters of monocytes and dendritic cells and 17 clusters of T cells. Examination of these clusters revealed that both CD14+CD16+intermediate and CD14dimCD16+nonclassical monocytes, as well as CD4+stem cell memory T (TSCM) cells, correlated with COVID-19 severity, coagulation factor levels, and/or inflammatory indicators. We also identified two nonclassical monocyte subsets distinguished by expression of the sugar residue 6-Sulfo LacNac (Slan). One of these subsets (Slanlo, nMo1) was depleted in moderately and severely ill patients, while the other (Slanhi, nMo2) increased with disease severity and was linked to CD4+T effector memory (TEM) cell frequencies, coagulation factors, and inflammatory indicators. Intermediate monocytes tightly correlated with loss of naive T cells as well as an increased abundance of effector memory T cells expressing the exhaustion marker PD-1. Our data suggest that both intermediate and non-classical monocyte subsets shape the adaptive immune response to SARS-CoV-2. In summary, our study provides both broad and in-depth characterization of immune cell phenotypes in response to COVID-19 and suggests functional interactions between distinct cell types during the disease.

One Sentence Summary

Use of mass cytometry on peripheral blood mononuclear cells from convalescent COVID-19 patients allows correlation of distinct monocyte and T lymphocyte subsets with clinical factors.
Global transcriptional regulators fine-tune the translational and metabolic machinery inEscherichia coliunder anaerobic fermentation
Authors: Iyer Mahesh S. , Pal Ankita , Srinivasan Sumana , Somvanshi Pramod R. , Venkatesh K.V.
Published: July 2020

Complex regulatory interactions between genetic and metabolic networks together confer robustness against external and internal perturbations in an organism such asEscherichia coli. In balanced exponential growth, this robustness is attributed to cost-effective metabolism by means of efficient resource allocation coordinated by the interplay of global transcriptional regulators with growth-rate dependent machinery. Here, we reappraise the role of global transcriptional regulators FNR, ArcA and IHF, integral to sustaining proteome-efficiency in anaerobic fermentative conditions, fundamental for optimal growth ofE. coli. We reveal at the transcriptome and metabolome level, that absence of these global regulators ensued a disruption of nitrogen homeostasis, overexpression of otherwise unnecessary or hedging genes and impairment in core bottleneck steps and amino acid metabolism. Notably, our findings emphasize their importance in optimizing the metabolic proteome resources essential for rapid exponential growth. Consequentially, the perturbations in the metabolic proteome as a result of deletion of global regulators unbalances the ribosomal proteome share imposing a high translation program, though at the expense of lowered efficiency. We illustrate that disruption of this inherent trade-off between metabolic and ribosomal proteomic investment eventually culminate to lowered growth rates. Despite no changes in gene expression related to glucose import, our findings elucidate that the accumulations of intracellular metabolites directly modulated by growth rate, negatively impacts the glucose uptake. Our results employing the proteome allocation theory and quantitative experimental measurements, suffices to explain the physiological consequences of altered translational and metabolic efficiency in the cell, driven by the loss of these global regulators.
CRISPR RNA-guided integrases for high-efficiency and multiplexed bacterial genome engineering
Authors: Vo Phuc Leo H. , Ronda Carlotta , Klompe Sanne E. , Chen Ethan E. , Acree Christopher , Wang Harris H. , Sternberg Samuel H.
Published: July 2020

Tn7-like transposons are pervasive mobile genetic elements in bacteria that mobilize using heteromeric transposase complexes comprising distinct targeting modules. We recently described a Tn7-like transposon fromVibrio choleraethat employs a Type I-F CRISPR–Cas system for RNA-guided transposition, in which Cascade directly recruits transposition proteins to integrate donor DNA downstream of genomic target sites complementary to CRISPR RNA. However, the requirement for multiple expression vectors and low overall integration efficiencies, particularly for large genetic payloads, hindered the practical utility of the transposon. Here, we present a significantly improved INTEGRATE (insertion of transposable elements by guide RNA-assisted targeting) system for targeted, multiplexed, and marker-free DNA integration of up to 10 kilobases at ~100% efficiency. Using multi-spacer CRISPR arrays, we achieved simultaneous multiplex insertions in three genomic loci, and facile multi-loci deletions when combining orthogonal integrases and recombinases. Finally, we demonstrated robust function in other biomedically- and industrially-relevant bacteria, and developed an accessible computational algorithm for guide RNA design. This work establishes INTEGRATE as a versatile and portable tool that enables multiplex and kilobase-scale genome engineering.
Precision long-read metagenomics sequencing for food safety by detection and assembly of Shiga toxin-producingEscherichia coliin irrigation water
Authors: Maguire Meghan , Kase Julie A. , Roberson Dwayne , Muruvanda Tim , Brown Eric W. , Allard Marc , Musser Steven M. , González-Escalona Narjol
Published: July 2020

Shiga toxin-producingEscherichia coli(STEC) contamination of agricultural water might be an important factor to recent foodborne illness and outbreaks involving leafy greens. Whole genome sequencing generation of closed bacterial genomes plays an important role in source tracking. We aimed to determine the limits of detection and classification of STECs by qPCR and nanopore sequencing using enriched irrigation water artificially contaminated withE. coliO157:H7 (EDL933). We determined the limit of STEC detection by qPCR to be 30 CFU/reaction, which is equivalent to 105CFU/ml in the enrichment. By using Oxford Nanopore’s EPI2ME WIMP workflow andde novoassembly with Flye followed by taxon classification with a k-mer analysis software (Kraken),E. coliO157:H7 could be detected at 103CFU/ml (68 reads) and a complete fragmentedE. coliO157:H7 metagenome-assembled genome (MAG) was obtained at 105-108CFU/ml. Using a custom script to extract theE. colireads, a completely closed MAG was obtained at 107-108CFU/ml and a complete, fragmented MAG was obtained at 105-106CFU/ml.In silicovirulence detection forE. coliMAGs for 105-108CFU/ml showed that the virulotype was indistinguishable from the spikedE. coliO157:H7 strain. We further identified the bacterial species in the un-spiked enrichment, including antimicrobial resistance genes, which could have important implications to food safety. We propose this workflow could be used for detection and complete genomic characterization of STEC from a complex microbial sample and could be applied to determine the limit of detection and assembly of other foodborne bacterial pathogens.

IMPORTANCE

Foodborne illness caused by Shiga toxin-producingE. coli(STEC) ranges in severity from diarrhea to hemolytic uremic syndrome and produce-related incidence is increasing. The pervasive nature ofE.colirequires not only detection, but also a complete genome to determine potential pathogenicity based onstxandeaegenes, serotype, and other virulence factors. We have developed a pipeline to determine the limits of nanopore sequencing for STECs in a metagenomic sample. By utilizing the current qPCR in the FDA Bacteriological Analytical Manual (BAM) Chapter 4A, we can quantify the amount of STEC in the enrichment and then sequence and classify the STEC in less than half the time as current protocols that require a single isolate. These methods have wide implications for food safety, including decreased time to STEC identification during outbreaks, characterization of the microbial community, and the potential to use these methods to determine the limits for other foodborne pathogens.
Disparate effects of metformin onMycobacterium tuberculosisinfection in diabetic and non-diabetic mice
Authors: Sathkumara Harindra D. , Hansen Karyna , Miranda-Hernandez Socorro , Govan Brenda , Rush Catherine M. , Henning Lars , Ketheesan Natkunam , Kupz Andreas
Published: July 2020

Comorbid type 2 diabetes poses a great challenge to the global control of tuberculosis. Here we assessed the efficacy of metformin (MET); an anti-diabetic drug, in mice infected with a very-low dose ofMycobacterium tuberculosis. In contrast to diabetic mice, infected non-diabetic mice that received the same therapeutic concentration of MET presented with significantly higher disease burden. This warrants further studies to investigate the disparate efficacy of MET against tuberculosis in diabetic and non-diabetic individuals.
Extratubular polymerized uromodulin induces leukocyte recruitment and inflammationin vivo
Authors: Immler Roland , Lange-Sperandio Bärbel , Steffen Tobias , Beck Heike , Roth Jonas , Hupel Georg , Pfister Frederik , Popper Bastian , Uhl Bernd , Mannell Hanna , Reichel Christoph A. , Vielhauer Volker , Scherberich Jürgen , Sperandio Markus , Pruenster Monika
Published: July 2020

Uromodulin (UMOD) is produced and secreted by tubular epithelial cells. Secreted UMOD polymerizes (pUMOD) within the lumen, where it regulates salt transport and protects the kidney from bacteria and stone formation. Under various pathological conditions, pUMOD accumulates within the tubular lumen and reaches extratubular sites where it may interact with renal interstitial cells. Here, we investigated the potential of extratubular pUMOD to act as a damage associated molecular pattern (DAMP) molecule thereby creating local inflammation. We found that intrascrotal and intraperitoneal injection of pUMOD induced leukocyte recruitmentin vivoand led to TNF-α secretion by F4/80 positive macrophages. Additionally, pUMOD directly affected vascular permeability and increased neutrophil extravasation independent of macrophage-released TNF-α. Interestingly, pUMOD did not directly upregulate adhesion molecules on endothelial cells and did not directly activate β2 integrins on neutrophils. In obstructed neonatal murine kidneys, we observed extratubular UMOD accumulation with tubular atrophy and leukocyte infiltrates. Finally, we found extratubular UMOD deposits associated with peritubular leukocyte infiltration in kidneys from patients with inflammatory kidney diseases. Taken together, we identified extratubular pUMOD as a strong inducer of leukocyte recruitment, underlining its critical role in mounting an inflammatory response in various kidneys pathologies.
Regulatory roles of 5′ UTR and ORF-internal RNAs detected by 3′ end mapping
Authors: Adams Philip P. , Baniulyte Gabriele , Esnault Caroline , Chegireddy Kavya , Singh Navjot , Monge Molly , Dale Ryan K. , Storz Gisela , Wade Joseph T.
Published: July 2020

Many bacterial genes are regulated by RNA elements in their 5′ untranslated regions (UTRs). However, the full complement of these elements is not known even in the model bacteriumEscherichia coli. Using complementary RNA-sequencing approaches, we detected large numbers of 3′ ends in 5′ UTRs and open reading frames (ORFs), suggesting extensive regulation by premature transcription termination. We documented regulation for multiple transcripts, including spermidine induction involving Rho and translation of an upstream ORF for an mRNA encoding a spermidine efflux pump. In addition to discovering novel sites of regulation, we detected short, stable RNA fragments derived from 5′ UTRs and sequences internal to ORFs. Characterization of three of these transcripts, including an RNA internal to an essential cell division gene, revealed that they have independent functions as sRNA sponges. Thus, these data uncover an abundance ofcis- andtrans-acting RNA regulators in bacterial 5′ UTRs and internal to ORFs.
Cortical recycling in high-level visual cortex during childhood development
Authors: Nordt Marisa , Gomez Jesse , Natu Vaidehi , Rezai Alex A. , Finzi Dawn , Kular Holly , Grill-Spector Kalanit
Published: July 2020

Human ventral temporal cortex (VTC) contains category-selective regions that respond preferentially to ecologically-relevant categories such as faces, bodies, places, and words, which are causally involved in the perception of these categories. How do these regions develop during childhood? We used functional MRI to measure longitudinal development of category-selectivity in school-age children over 1 to 5 years. We discovered that from young childhood to the teens, face- and word-selective regions in VTC expand and become more category-selective, but limb-selective regions shrink and lose their preference for limbs. Critically, as a child develops, increases in face- and word-selectivity are directly linked to decreases in limb-selectivity, revealing that during childhood limb-selectivity in VTC is repurposed into word- and face-selectivity. These data provide evidence for cortical recycling during childhood development. This has important implications for understanding typical as well as atypical brain development and necessitates a rethinking of how cortical function develops during childhood.
Computational and Molecular Dynamics Simulation Approach To Analyze the Impact ofXPDGene Mutation on Protein Stability and Function
Authors: Panchal Nagesh Kishan , Bhale Aishwarya , Verma Vinod Kumar , Beevi Syed Sultan
Published: July 2020

XPDacts as a functional helicase and aids in unwinding double helix around damaged DNA, leading to efficient DNA repair. Mutations ofXPDgive rise to DNA-repair deficiency diseases and cancer proneness. In this study, cancer-causing missense mutation that could inactivate helicase function and hinder its binding with other complexes were analysed using bioinformatics approach. Rigorous computational methods were employed to understand the molecular pathogenic profile of mutation. The mutant model with the desired mutation was built with I-TASSER. GROMACS 5.0.1 was used to evaluate the effect of a mutation on protein stability and function. Of the 276 missense mutations, 64 were found to be disease-causing. Out of these 64, seven were of cancer-causing mutations. Among these, we evaluated K48R mutation in a computational simulated environment to determine its impact on protein stability and function since K48 position was ascertained to be highly conserved and substitution with arginine could impair theXPDactivity. Molecular Dynamic Simulation and Essential Dynamics analysis showed that K48R mutation altered protein structural stability and produced conformational drift. Our predictions thus revealed that K48R mutation could impair theXPDhelicase activity and affect its ability to repair the damaged DNA, thus augmenting the risk for cancer.
Generalized Hidden Markov Models for Phylogenetic Comparative Datasets
Authors: Boyko James D. , Beaulieu Jeremy M.
Published: July 2020

Hidden Markov models (HMM) have emerged as an important tool for understanding the evolution of characters that take on discrete states. Their flexibility and biological sensibility make them appealing for many phylogenetic comparative applications.

Previously available packages placed unnecessary limits on the number of observed and hidden states that can be considered when estimating transition rates and inferring ancestral states on a phylogeny.

To address these issues, we expanded the capabilities of the R packagecorHMMto handlen-state andn-character problems and provide users with a streamlined set of functions to create custom HMMs for any biological question of arbitrary complexity.

We show that increasing the number of observed states increases the accuracy of ancestral state reconstruction. We also explore the conditions for when an HMM is most effective, finding that an HMM is an appropriate model when the degree of rate heterogeneity is moderate to high.

Finally, we demonstrate the importance of these generalizations by reconstructing the phyllotaxy of the ancestral angiosperm flower. Partially contradicting previous results, we find the most likely state to be a whorled perianth, whorled androecium, whorled gynoecium. The difference between our analysis and previous studies was that our modeling explicitly allowed for the correlated evolution of several flower characters.
Novel mechanisms of efflux-mediated levofloxacin resistance and reduced amikacin susceptibility inStenotrophomonas maltophilia
Authors: Dulyayangkul Punyawee , Calvopiña Karina , Heesom Kate J. , Avison Matthew B.
Published: July 2020

Fluoroquinolone resistance inStenotrophomonas maltophiliais multi-factorial, but the most significant factor is production of efflux pumps, particularly SmeDEF. Here we report that mutations in the glycosyl transferase genesmlt0622inS. maltophiliaK279a mutant K M6 cause constitutive activation of SmeDEF production, leading to elevated levofloxacin MIC. Selection of a levofloxacin-resistant K M6 derivative, K M6 LEVR, allowed identification of a novel two-component regulatory system, Smlt2645/6 (renamed as SmaRS). The sensor kinase Smlt2646 (SmaS) is activated by mutation in K M6 LEVRcausing over-production of two novel ABC transporters and the known aminoglycoside efflux pump SmeYZ. Over-production of one ABC transporter, Smlt1651-4 (renamed as SmaCDEF) causes levofloxacin resistance in K M6 LEVR. Over-production of the other ABC transporter, Smlt2642/3 (renamed SmaAB) and SmeYZ both contribute to the elevated amikacin MIC against K M6 LEVR. Accordingly, we have identified two novel ABC transporters associated with antimicrobial drug resistance inS. maltophilia, and two novel regulatory systems whose mutation causes resistance to levofloxacin, clinically important as a promising drug for monotherapy against this highly resistant pathogen.
Probing the dissonance among the diagnostic outputs of multiple approaches used for detection of Methicillin-resistant Staphylococcus aureus (MRSA)
Authors: Dahiya Ujjwal Ranjan , Sikidar Arnab , Sharma Priyanka , Rawat Chitra , Dhawan Benu , Kapil Arti , Elangovan Ravikrishnan , Kalyanasundaram Dinesh
Published: July 2020

Methicillin resistant staphylococcus aureus (MRSA) is an extremely infectious hospital acquired bacterial pathogen often found in post-surgical patients globally. Early detection of such pathogens is a critical requirement to eliminate or reduce the incidence of anti-microbial resistance as well as for effective management of the disease. Despite the development of multiple biochemical, microbiological and nucleic acid amplifications techniques (NAATs), conventional culture methods are widely used clinically owing to high variability between the methods, technical skills and infrastructural needs. Further, multiple reports suggest significant variation among diagnostic output for MRSA detection. This work attempts to probe the discordance among the diagnostic output of three commonly used methods, while trying to understand the underlying cause of variability. MRSA detection on 217 clinical pus isolates was carried out using three different methods namely, conventional culture method, qPCR-based amplification and a modern LAMP based detection approach. Also, to confirm the presence of MRSA and distinguish from coagulase-negative staphylococci (CoNS), as well as to investigate the observed differences between qPCR and LAMP outputs, melt curve analysis was performed on discordant samples. LAMP based MRSA detection was found to be the optimum method. In summary, this study evaluates the diagnostic efficiency of the different detection methods, while probing for possible explanations for the observed differences.
Timing of mating, reproductive status and resource availability in relation to migration in the painted lady butterfly,Vanessa cardui
Authors: Stefanescu Constantí , Ubach Andreu , Wiklund Christer
Published: July 2020

In many migratory insects, migration occurs during the pre-reproductive phase of the life cycle. This trait probably arises from a trade-off between migration and reproduction and in females has been termed as the ‘oogenesis-flight syndrome’. However, the generality of this syndrome has been questioned, especially for monomorphic insects. We studied the relationship between migration and reproduction in the highly cosmopolitan painted lady butterfly, which in the Palaearctic undertakes the longest known multi-generational migration circuit of any insect. We tested for the oogenesis-flight syndrome in both spring and autumn migrants in two regions linked by migration, North Africa and northern Spain. Field observations were combined with laboratory experiments to determine the lifespan and the age at first mating to unravel the reproductive strategy observed in individuals captured in the wild. Females and males wait on average around 5–6 days before mating, and field data revealed that mating frequencies increase rapidly once females reach a medium wing wear category. There were seasonal differences in mating frequencies in the study regions depending on whether the region acted as a source or as a destination for migrants, and in the latter case there were almost twice as many mated females. Moreover, about 80% of females collected during migratory flights were unmated, the remaining females having mated only very recently. Our results thus strongly indicate that the painted lady fulfils the oogenesis-flight syndrome, as migration is concentrated in its relatively short pre-reproductive period. Field data also showed a high positive correlation between mating frequency and host plant abundance, which suggests that mated females have the ability to locate potential breeding areas. This, together with the very high fecundity estimated from over 1000 eggs in laboratory trials, makes the painted lady one of the most successful migratory insects on Earth.
Phenotypical predictors of Restless Legs Syndrome in pregnancy and their association with basal ganglia and the limbic circuits
Authors: Chechko Natalia , Lefort-Besnard Jeremy , Goecke Tamme W. , Frensch Markus , Schnakenberg Patricia , Stickel Susanne , Bzdok Danilo
Published: July 2020

The pregnancy-related restless legs syndrome (RLS) is thought to have a multifactorial etiology. However, the reason behind the manifestation of RLS during pregnancy remains largely elusive.

A neurological and obstetrical cohort of 308 postpartum women was screened for RLS symptoms twice: 1 to 6 days (T0) and 12 weeks postpartum (T1). 57 participants were identified as affected by pregnancy-associated RLS. The clinical and anamnestic indicators of the condition were assessed by a pattern-learning classifier trained to predict the RLS status. Structural MRI was obtained from 25 of the 57 participants with RLS history in pregnancy. In this sample, a multivariate two-window algorithm was employed to systematically chart the relationship between brain structures and phenotypical predictors.

The RLS prevalence rate in our sample was 19% (n=57), with the women suffering from RLS being older, more often unmarried, affected by gestational diabetes and having been more exposed to stressful life events. A history of RLS and the severity and frequency of repetitive compulsive movements were found to be the strongest predictors of RLS manifestation. In the RLS group, high cortisol levels, being married and receiving iron supplements were found to be associated with increased volumes in the bilateral striatum.

Investigating pregnancy-related RLS in a frame of brain phenotype modes may help shed light on the heterogeneity of the condition.
FOXP1 negatively regulates intrinsic excitability in D2 striatal projection neurons by promoting inwardly rectifying and leak potassium currents
Authors: Khandelwal Nitin , Cavalier Sheridan , Rybalchenko Volodymyr , Kulkarni Ashwinikumar , Anderson Ashley G. , Konopka Genevieve , Gibson Jay R.
Published: July 2020

Heterozygous loss-of-function mutations in the transcription factorFOXP1are strongly associated with autism. Dopamine receptor 2 expressing (D2) striatal projection neurons (SPNs) in heterozygousFoxp1(Foxp1+/−) mice have higher intrinsic excitability. To understand the mechanisms underlying this alteration, we examined SPNs with cell-type specific homozygousFoxp1deletion to study cell-autonomous regulation byFoxp1. As inFoxp1+/−mice, D2 SPNs had increased intrinsic excitability with homozygousFoxp1deletion. This effect involved postnatal mechanisms. The hyperexcitability was mainly due to down-regulation of two classes of potassium currents: inwardly rectifying (KIR) and leak (KLeak). Single-cell RNA sequencing data from D2 SPNs withFoxp1deletion indicated the down-regulation of transcripts of candidate ion channels that may underlie these currents:Kcnj2andKcnj4for KIRandKcnk2for KLeak. ThisFoxp1-dependent regulation was neuron-type specific since these same currents and transcripts were either unchanged, or very little changed, in D1 SPNs with cell-specificFoxp1deletion. Our data are consistent with a model where FOXP1 negatively regulates the excitability of D2 SPNs through KIRand KLeakby transcriptionally activating their corresponding transcripts. This, in turn, provides a novel example of how a transcription factor may regulate multiple genes to impact neuronal electrophysiological function that depends on the integration of multiple current types – and do this in a cell-specific fashion. Our findings provide initial clues to altered neuronal function and possible therapeutic strategies not only for FOXP1-associated autism but also for other autism forms associated with transcription factor dysfunction.
A biaryl-linked tripeptide fromPlanomonosporaleads to widespread class of minimal RiPP gene clusters
Authors: Zdouc Mitja M. , Alanjary Mohammad M. , Zarazúa Guadalupe S. , Maffioli Sonia I. , Crüsemann Max , Medema Marnix H. , Donadio Stefano , Sosio Margherita
Published: July 2020

Microbial natural products impress by their bioactivity, structural diversity and ingenious biosynthesis. While screening the rare actinobacterial genusPlanomonospora,cyclopeptides1Aand1Bwere discovered, featuring an unusual Tyr-His biaryl-bridging across a tripeptide scaffold, with the sequencesN-acetyl-Tyr-Tyr-His (1A) andN-acetyl-Tyr-Phe-His (1B). Genome analysis of the1Aproducing strain pointed to-wards a ribosomal synthesis of1A, from a pentapeptide precursor encoded by the tiny 18-nucleotide genebycA,to our knowledge the smallest gene ever reported. Further, biaryl instalment is performed by the closely linked genebycB,encoding a cytochrome P450 monooxygenase. Biosynthesis of1Awas confirmed by heterologous production inStreptomyces,yielding the mature product. Bioinformatic analysis of related cytochrome P450 monooxygenases indicated that they constitute a widespread family of pathways, associated to 5-aa coding sequences in approximately 200 (actino)bacterial genomes, all with potential for a biaryl linkage between amino acids 1 and 3. We propose the name biarylicins for this newly discovered family of RiPPs.
Numerical analysis of electrically conductive fillers of composites for aircraft lightning strike protection
Authors: Lesiuk Igor , Katunin Andrzej
Published: July 2020

Purpose

This paper aims to present a numerical analysis and comparison of two types of conductive fillers of polymeric composites subjected to lightning strikes.

Design/methodology/approach

Two types of conductive fillers were considered in the developed numerical models of electrically conductive composites: carbon nanotubes and polyaniline. For these fillers, the representative volume elements were developed to consider distribution of the particles that ensures percolation and homogenization of the materials within the Eshelby-based semi-analytical mean-field homogenization approach. The performed numerical analyses allowed determination of effective volume fractions of conducting particles, resistivity and conductivity tensors, and finally the current density for the simulated materials subjected to lightning strike.

Findings

The obtained results allowed for comparison of electrical conductivity of two simulated materials. It was observed that besides fair results obtained in the previous studies for intrinsically conducting polymers as fillers of composites dedicated for lightning strike protection, the composites filled with carbon nanotubes reveal much better conductivity.

Practical implications

The presented simulation results can be considered as initial information for further experimental tests on electrical conductivity of such materials.

Originality/value

The originality of the paper lies in the proposed design and simulation procedures of conductive composites as well as the comparison of selected composites dedicated for lightning strike protection as the most intensively developed materials for this purpose.
Robust output feedback control of fixed-wing aircraft
Authors: Raza Abid , Malik Fahad Mumtaz , Khan Rameez , Mazhar Naveed , Ullah Hameed
Published: July 2020

Purpose

This paper aims to devise a robust controller for the non-linear aircraft model using output feedback control topology in the presence of uncertain aerodynamic parameters.

Design/methodology/approach

Feedback linearization-based state feedback (SFB) controller is considered along with a robust outer loop control which is designed using Lyapunov’s second method. A high-gain observer (HGO) in accordance with the separation principle is used to implement the output feedback (OFB) control scheme. The robustness of the controller and observer is assessed by introducing uncertain aerodynamics coefficients in the dynamic model. The proposed scheme is validated using MATLAB/SIMULINK.

Findings

The efficacy of the proposed scheme is authenticated with the simulation results which show that HGO-based OFB control achieves the SFB control performance for a small value of the high-gain parameter in the presence of uncertain aerodynamic parameters.

Originality/value

A HGO for the non-linear model of aircraft with uncertain parameters is a novel contribution which could be further used for the unmanned aerial vehicles autopilot, flight trajectory tracking and path following.
Assessing the credibility of Web information by university students: findings from a case study in Iran
Authors: Keshavarz Hamid
Published: July 2020

Purpose

The purpose of this paper is to explore how university students assess the credibility of diverse information available on the Web.

Design/methodology/approach

This paper used applied study and was conducted using the survey-descriptive method. Using a randomized stratified sampling method and the Cochran sampling formula, a sample including 380 student participants was selected from Shahid Beheshti University, Tehran, Iran. Data were gathered by administrating a validated questionnaire including eight components of ethics, writing style, website appearance, website identity, professional information, accuracy, usability and interaction. Data were analyzed by software SPSS 20.0 and LISREL 8.7.

Findings

Confirmatory factor analysis using structural equation modeling indicated that the overall framework is reliable according to the goodness of fit indices for the measurement and structural models showing a high quality on measuring the variable in the context studied. Findings also showed that the components usability, interaction, accuracy, website appearance, writing style, professional information, ethics and website identity had the standard relevance.

Practical implications

Users paid more attention to semantic- and expertise-related features compared to characteristics of the source and its authority. Such preference should be taken into account by providers when producing information and students when evaluating information.

Originality/value

The framework underlying this research had the required quality incorporating a set of most important criteria for exploring Web information evaluation behavior by the students, which is also useful for future related studies.
Changing the course of IfATE: healthier higher and degree apprenticeships for regulated healthcare professionals
Authors: Lillis Finbar , Varetto Angelo
Published: July 2020

Purpose

The purpose of this paper is to show how and why government discoursal constraints have obstructed the development of viable degree apprenticeships for regulated healthcare professionals working in England and suggests some ways these constraints can now be managed and overcome.

Design/methodology/approach

The study uses an analysis of published literature, reviews of government and health professional body policies and regulations and semi-structured interviews recorded with those leading on the development of degree apprenticeships in healthcare-regulated professions.

Findings

Once created, a bureaucracy tends to look for ways to control discourse, to sustain itself and to extend its reach. In doing so, fault lines may be exposed which undermine the position of that bureaucracy, but it will continue to control discourses to maintain power over those it requires to act. There is no pedagogical need for End Point Assessment (EPA) to measure the competence of regulated healthcare professionals. The paper produces evidence to show how meeting health professional registration requirements is a sufficient metric for measuring successful degree apprenticeship outcomes.

Research limitations/implications

This paper examined current practices relating to the registered nurse and nursing associate degree apprenticeships only. The validity of EPA for measuring occupational competence should be further investigated.

Practical implications

The NHS and other public service organisations should use these findings to re-examine and challenge the requirements for EPA in degree apprenticeships for all regulated professions.

Originality/value

Understanding how “centering” bureaucracies control discourse in their interests can help those in their orbit find ways to challenge and alter the course of policy.
Research Productivity Index (RPI): a new metric for measuring universities’ research productivity
Authors: Halaweh Mohanad
Published: July 2020

Purpose

This paper aims to propose a new metric, called the Research Productivity Index (RPI), which can be used to measure universities’ research productivity and benchmark them accordingly at both national and global levels.

Design/methodology/approach

The paper used a partial-factor productivity measurement as the basis to develop RPI, which considers the ratio of total weighted publications (outputs) to the used input (affiliated researchers). To demonstrate the applicability of the RPI, data were collected from Scopus to assess the research productivity of a university in the UAE, as an example. The methodological steps (algorithm) were demonstrated using mathematical and query functions to extract the required data from the Scopus data set and then compute the RPI value.

Findings

A new effective and objective metric was developed for measuring universities’ research productivity.

Practical Implications

This paper suggests that Scopus could use RPI as a metric for measuring the research productivity of each university. RPI can be used by university administrators and government decision-makers to evaluate and rank/benchmark institutions’ research productivity. They can consequently make more effective decisions with regard to the efficient allocation of research budgets and funding.

Originality/value

This paper distinguishes between measuring research impact and research productivity. It proposes RPI for measuring the latter, whereas most existing metrics measure the former. RPI is an objective measurement, as it is calculated based on a constant period of time, three years, and takes into consideration the university size (i.e. affiliated researchers) in addition to the quality and quantity (total) of research outcomes.
Students’ knowledge and expectations about sustainable food systems in higher education
Authors: Migliorini Paola , Wezel Alexander , Veromann Eve , Strassner Carola , Średnicka-Tober Dominika , Kahl Johannes , Bügel Susanne , Briz Teresa , Kazimierczak Renata , Brives Hélène , Ploeger Angelika , Gilles Ute , Lüder Vanessa , Schleicher-Deis Olesa , Rastorgueva Natalia , Tuccillo Fabio , Talgre Liina , Kaart Tanel , Ismael Diana , Rembiałkowska Ewa
Published: July 2020

Purpose

To clarify needs and requests of the young generation to the contemporary and future education on food systems, this paper aims to examine the following issues: students’ background knowledge, students’ behaviour as consumers and food citizenship, most interesting topics of SFS for students and students’ preferences and expectations in developing different skills, topics and preferences in teaching/learning methods.

Design/methodology/approach

This study was performed as an online-survey amongst eight European Universities in seven European Union (EU) countries to which 1,122 students responded. Data was analysed with descriptive and multivariate statistical analyses.

Findings

Taste and Health are the most important values and motives that influence students’ food buying and consumption decisions, but significant differences were found amongst students from different universities and countries. The most important topics for students for future teaching courses are “organic food”, “fair trade”, “organic agriculture” and most important skills to learn are “ability to make a judgement and justify decisions” and the “ability to create and innovate”. Excursions and field trips as teaching methods was given the highest ranks.

Research limitations/implications

Different study programmes and cultural backgrounds of the participating students in the different universities could be a limiting factor for the interpretation of some results.

Originality/value

These results provide a basis for improvement of higher education in the EU towards sustainable food systems based on experiential learning/teaching methods.
Accruals quality and leverage adjustments
Authors: Dufour Dominique , Luu Philippe , Teller Pierre
Published: July 2020

Purpose

This paper analyses the role of accounting information quality on leverage adjustments. More specifically, the authors investigate whether a better accounting information leads to a higher speed of adjustment to the target financial leverage.

Design/methodology/approach

The authors use a two-step method. They first estimate the target financial structure and then the influence of accruals quality on the speed of adjustment to this target. The study sample consists of French listed companies in the CAC All-Tradable index. The sample contains 210 companies and 1,713 observations.

Findings

Accounting literature showed the positive influence of accounting quality on financial management. The study findings are in line with these results. The authors give evidence of that a better quality of accruals is associated with a greater speed of adjustment.

Research limitations/implications

A common limitation in this field is the use of proxies. This makes results harder to generalize. For this reason, the authors implemented several models to improve the robustness of their results.

Practical implications

The authors give evidence that firms have an incentive to disclose a good-quality accounting information. A weak accounting quality prevents firms from adjusting their leverage to their financial target and therefore reduce their value.

Social implications

This work shows the need for accounting standardization bodies to strive to produce accounting standards allowing the production of high-quality accounting information. In a teaching dimension, these results highlight the importance in corporate finance of acquiring expertise in quality accounting information analysis.

Originality/value

This work is original because the authors study the influence of accounting quality on speed of adjustments of firms operating in the same legal environment and using the same accounting standards, when previous work compared different accounting frameworks. The French context is characterized by the weakness of market mechanisms and the important role of banks. These characteristics are known to reduce the role of accounting information in financing process. This result is interesting because the authors demonstrate that firms operating in this context still have an incentive in producing high accounting quality information.
How does knowledge heterogeneity affect transactive memory system in innovation? Evidence from a field study
Authors: Zhang Ruilin , Wang Jun , Hao Jin-Xing
Published: July 2020

Purpose

The dispute over the benefit of diversity on the transactive memory system (TMS) has attracted the attention with the development of global collaboration. This paper aims to discover how knowledge heterogeneity (KH), categorized as explicit and tacit KH, affects TMS and to test the mediation effect of innovation climate (IC).

Design/methodology/approach

Data from a 6-month field study of 207 research and development (R&D) members and 7 expertize observers were analyzed by partial least squares structure equation model. Robustness check and Barron and Kenny mediation test were used to evaluate the model and confirm the mediation effect.

Findings

Tacit KH of R&D team negatively influences the development of TMS. Furthermore, IC partially mediates tacit KHs’ negative influence on the development of TMS.

Research limitations/implications

These results distinguish the different influence of explicit and tacit KH on TMS and explore the mediating role of IC that has been confirmed affecting the development of TMS.

Practical implications

These results could motivate practitioners to address more attention to tacit KH, IC and the development of TMS in the R&D team members composition.

Originality/value

This study contributes not only to elucidate the different influence of explicit and tacit KH on TMS but also to the appropriate members composition of R&D team by considering the relationships among KH, IC, TMS and innovation performance.
International rivalry and global business leadership: an historical perspective
Authors: Casson Mark
Published: July 2020

Purpose

This paper aims to introduce economic history as a new stream of international business (IB) research. It offers a long-term perspective on how the IB has evolved over time, focussing on the interplay between multinational enterprise and the nation state.

Design/methodology/approach

The paper uses existing scholarly literature on international economic history to develop eight key propositions regarding the interface between the politics and economics of foreign direct investment (FDI).

Findings

There is a rivalry between nation states and competition between firms. These two forms of conflict interact. Nations use their leading firms as instruments of international policy while leading firms rely on political and financial support from home nations. Using historical evidence and cross-country comparisons, the paper explains has the scale and scope in IB activity have changed dramatically over time.

Research limitations/implications

There is scope for more detailed historical studies on national policies towards inward and outward FDI.

Practical implications

It is important to see the recent international economic policies of China in a long-run historical perspective and to appreciate the similarities between its policies and those of other countries in the past.

Social implications

Many of the potential economic gains generated by FDI may be lost through an excessive commitment of resources to the pursuit of military power as a foundation for international political power.

Originality/value

This paper challenges IB researchers to widen their horizons.
How do mid-senior multinational officers perceive shared leadership for military teams? A qualitative study
Authors: Cakiroglu Sultan Serkan , Caetano António , Costa Patrícia
Published: July 2020

Purpose

The purpose of this study is to explore the military team members’ (mid-senior multinational officers’) perceptions of shared leadership and analyze the facilitation of shared leadership in military teams.

Design/methodology/approach

The sample size was 20 interviewees that participants must hold leadership positions at the mid-senior management level and from NATO member countries. To analyze the data, the authors used Gioia’s thematic analysis methodology (Gioiaet al., 2013) and manual coding rather than computer usage for the analysis, due to the small data pool and their proficiency in literature.

Findings

Complexity and the new information era force military organizations toward the change and that with shared leadership they can even change the organization’s culture. The final framework highlights five main dimensions that emerged from mid-multinational military officers’ experience: driving forces of change, triggers to shared leadership, specific cases shared leadership, operational team environment and operational team characteristics. Results of the study supported that driving forces of change comprised the primary factor affecting shared leadership in military project teams.

Practical implications

The Headquarter environment (strategic and operational planning) and planning were critical factors for the successful implementation and development of shared leadership in military project teams. Thus, military organizations could easily implement the shared leadership approach in the military research teams and planning teams.

Originality/value

The authors present a framework of leadership change context for military teams, which depicts how shared leadership could be implemented differently in military teams.