bluuebunny/crossref_metadata_2025 huggingface dataset:
LC3B phosphorylation regulates FYCO1 binding and directional transport of autophagosomes
Authors: Nieto-Torres Jose L. , Shanahan Sean-Luc , Chassefeyre Romain , Landeras-Bueno Sara , Encalada Sandra E. , Hansen Malene
Published: May 2020

Macroautophagy (hereafter referred to as autophagy) is a conserved process that promotes cellular homeostasis through the degradation of cytosolic components, also known as cargo. During autophagy, cargo is sequestered into double-membrane vesicles called autophagosomes, which are predominantly transported in the retrograde direction to the perinuclear region to fuse with lysosomes, thus ensuring cargo degradation [1]. The mechanisms regulating directional autophagosomal transport remain unclear. The ATG8 family of proteins associate with autophagosome membranes [2] and play key roles in autophagy, such as the movement of autophagosomes. This is achieved via the interaction of ATG8 with adaptor proteins, including FYCO1, a protein involved in the anterograde transport of autophagosomes toward the cell periphery [1,3–5]. We previously reported that phosphorylation of LC3B/ATG8 on threonine 50 (LC3B-T50) by the Hippo kinase STK4 is required for autophagy through unknown mechanisms [6]. Here, we show that LC3B-T50 phosphorylation decreases the interaction between LC3B and FYCO1, which in turn regulates the starvation-induced perinuclear positioning of autophagosomes. Moreover, non-phosphorylatable LC3B-T50A aberrantly switches the predominant retrograde movement of autophagosomes to anterograde movement towards the cell periphery in multiple cell types, including in mouse primary hippocampal neurons. Our data support a role of a nutrient-sensitive STK4–LC3B–FYCO1 axis in the regulation of the directional transport of autophagosomes via the post-translational regulation of LC3B. Given that autophagy is impaired in many human conditions, including neurodegenerative diseases, our findings may highlight new principles of vesicle transport regulation critical for disease etiology.

Graphical abstract
A complex resistance locus inSolanum americanumrecognizes a conservedPhytophthoraeffector
Authors: Witek Kamil , Lin Xiao , Karki Hari S , Jupe Florian , Witek Agnieszka I , Steuernagel Burkhard , Stam Remco , van Oosterhout Cock , Fairhead Sebastian , Cocker Jonathan M , Bhanvadia Shivani , Barrett William , Wu Chih-Hang , Adachi Hiroaki , Song Tianqiao , Kamoun Sophien , Vleeshouwers Vivianne GAA , Tomlinson Laurence , Wulff Brande BH , Jones Jonathan DG
Published: May 2020

Late blight caused byPhytophthora infestansgreatly constrains potato production. ManyResistance (R)genes were cloned from wildSolanumspecies and/or introduced into potato cultivars by breeding. However, individualRgenes have been overcome byP. infestansevolution; durable resistance remains elusive. We positionally cloned a newRgene,Rpi-amr1, fromSolanum americanum, that encodes an NRC helper-dependent CC-NLR protein.Rpi-amr1confers resistance in potato to all 19P. infestansisolates tested. Using association genomics and long-read RenSeq, we defined eight additionalRpi-amr1alleles from differentS. americanumand related species. Despite only ∼90% identity between Rpi-amr1 proteins, all confer late blight resistance but differentially recognizeAvramr1orthologs and paralogs. We propose thatRpi-amr1gene family diversity facilitates detection of diverse paralogs and alleles of the recognized effector, enabling broad-spectrum and durable resistance againstP. infestans.
Sequence characterization and molecular modeling of clinically relevant variants of the SARS-CoV-2 main protease
Authors: Cross Thomas J. , Takahashi Gemma R. , Diessner Elizabeth M. , Crosby Marquise G. , Farahmand Vesta , Zhuang Shannon , Butts Carter T. , Martin Rachel W.
Published: May 2020

The SARS-CoV-2 main protease (Mpro) is essential to viral replication and cleaves highly specific substrate sequences, making it an obvious target for inhibitor design. However, as for any virus, SARS-CoV-2 is subject to constant selection pressure, with new Mpromutations arising over time. Identification and structural characterization of Mprovariants is thus critical for robust inhibitor design. Here we report sequence analysis, structure predictions, and molecular modeling for seventy-nine Mprovariants, constituting all clinically observed mutations in this protein as of April 29, 2020. Residue substitution is widely distributed, with some tendency toward larger and more hydrophobic residues. Modeling and protein structure network analysis suggest differences in cohesion and active site flexibility, revealing patterns in viral evolution that have relevance for drug discovery.
Impaired Layer Specific Retinal Vascular Reactivity Among Diabetic Subjects
Authors: Singer Maxwell , Ashimatey Bright S. , Zhou Xiao , Chu Zhongdi , Wang Ruikang K. , Kashani Amir H.
Published: May 2020

Purpose

To investigate layer specific retinal vascular reactivity (RVR) in capillaries of diabetic subjects with no or mild non-proliferative diabetic retinopathy (NPDR).

Methods

A previously described nonrebreathing apparatus was used to deliver room air, 5% CO2, or 100% O2to 41 controls and 22 diabetic subjects (with mild or no NPDR) while simultaneously acquiring fovea-centered 3×3mm2Swept-Source Optical Coherence Tomography Angiography. Vessel skeleton density (VSD) and vessel diameter index (VDI) were calculated for each gas condition for the superficial retinal layer (SRL) and deep retinal layer (DRL). The superficial layer analysis excluded regions of arterioles and venules. Data analysis was performed using mixed factorial analysis of covariance stratified by diabetic status. All models were adjusted for age, gender, and hypertension.

Results

Among controls, there was a significant difference in capillary VSD between all gas conditions (p<0.001). This difference was present in both the SRL and DRL. Among diabetics, there was no significant difference in response to CO2conditions in the SRL (p=0.072), and a blunted response to both CO2and O2in the DRL. A significant gas effect was detected in the capillary VDI in the SRL of controls (p=0.001), which was driven by higher VDI in the oxygen condition compared to that of carbon dioxide.

Conclusions

Impairment in RVR in diabetic subjects is driven largely by a decrease in the magnitude of the capillary response to O2in the DRL as well as almost complete attenuation of capillary CO2response in all layers. These layer and gas specific impairments in diabetics seem to occur early in the disease and to be driven primarily at the capillary level.
Cephalosporins target quorum sensing and suppress virulence ofPseudomonas aeruginosainCaenorhabditis elegansinfection model
Authors: Kumar Lokender , Brenner Nathanael , Brice John , Klein-Seetharaman Judith , Sarkar Susanta K.
Published: May 2020

Pseudomonas aeruginosautilizes a chemical social networking system referred to as quorum sensing (QS) to strategically co-ordinate the expression of virulence factors and biofilm formation. Virulence attributes damage the host cells, impair the host immune system, and protect bacterial cells from antibiotic attack. Thus, anti-QS agents may act as novel anti-infective therapeutics to treatP. aeruginosainfections. The present study was performed to evaluate the anti-QS, anti-biofilm, and anti-virulence activity of β-lactam antibiotics (carbapenems and cephalosporins) againstP. aeruginosa. The anti-QS activity was quantified usingChromobacterium violaceumCV026 as a QS reporter strain. Our results showed that cephalosporins including cefepime (CP), ceftazidime (CF), and ceftriaxone (CT) exhibited potent anti-QS and anti-virulence activities againstP. aeruginosaPAO1. These antibiotics significantly impaired motility phenotypes, decreased pyocyanin production, and reduced the biofilm formation byP. aeruginosaPAO1. In the present study, we studied isogenic QS mutants of PAO1: ΔLasR, ΔRhlR, ΔPqsA, and ΔPqsR and found that the levels of virulence factors of antibiotic-treated PAO1 were comparable to QS mutant strains. Molecular docking predicted high binding affinities of cephalosporins for the ligand-binding pocket of QS receptors (CviR, LasR, and PqsR). In addition, our results showed that the anti-microbial activity of aminoglycosides increased in the presence of sub-inhibitory concentrations (sub-MICs) of CP againstP. aeruginosaPAO1. Further, utilizingCaenorhabditis elegansas an animal model for thein vivoanti-virulence effects of antibiotics, cephalosporins showed a significant increase inC. eleganssurvival by suppressing virulence factor production inP. aeruginosa. Thus, our results indicate that cephalosporins might provide a viable anti-virulence therapy in the treatment of infections caused by multi-drug resistantP. aeruginosa.
SR7 - a dual function antisense RNA fromBacillus subtilis
Authors: Haq Inam Ul , Müller Peter , Brantl Sabine
Published: May 2020

Here, we describe SR7, a dual-function antisense RNA from theBacillus subtilischromosome. This RNA was earlier published as the SigB-dependent regulatory RNA S1136 and reported to reduce the amount of the small ribosomal subunit under ethanol stress. We found that the 5’ portion of SR7 encodes a small protein composed of 39 amino acids which we designated SR7P. It is translated from a 185 nt SigB-dependent mRNA under five different stress conditions and a longer SigB-independent RNA constitutively. Two- to three-fold higher amounts of SR7P were detected inB. subtiliscells exposed to salt, ethanol or heat stress. Co-elution experiments with SR7PC-FLAGand Far-Western blotting demonstrated that SR7P interacts with the glycolytic enzyme enolase. Enolase is a scaffolding component of theB. subtilisdegradosome where it interacts with RNase Y and phosphofructokinase PfkA. We found that SR7P increases the amount of RNase Y bound to enolase without affecting PfkA. RNA does not bridge the SR7P-enolase-RNase Y interaction.In vitro-degradation assays with the known RNase Y substratesyitJandrpsOmRNA revealed enhanced enzymatic activity of enolase-bound RNase Y in the presence of SR7P. Northern blots showed a major effect of enolase and a minor effect of SR7P on the half-life ofrpsOmRNA indicating a fine-tuning role of SR7P in RNA degradation. Moreover, SR7P impacts survival ofB. subtilisunder stress conditions. We suggest that the SR7P-dependent modification of the degradosome affects targets in different physiological pathways.
Structural analysis of the SARS-CoV-2 methyltransferase complex involved in coronaviral RNA cap creation
Authors: Krafcikova Petra , Silhan Jan , Nencka Radim , Boura Evzen
Published: May 2020

COVID-19 pandemic is caused by the SARS-CoV-2 virus that has several enzymes that could be targeted by antivirals including a 2’-O RNA methyltransferase (MTase) that is involved in the viral RNA cap formation; an essential process for RNA stability. This MTase is composed of two nonstructural proteins, the nsp16 catalytic subunit and the activating nsp10 protein. We have solved the crystal structure of the nsp10-nsp16 complex bound to the pan-MTase inhibitor sinefungin in the active site. Based on the structural data we built a model of the MTase in complex with RNA that illustrates the catalytic reaction. A structural comparison to the Zika MTase revealed low conservation of the catalytic site between these two RNA viruses suggesting preparation of inhibitors targeting both these viruses will be very difficult. Together, our data will provide the information needed for structure-based drug design.
Regulation by the Pitcher Plant Sarracenia purpurea of the Structure of its Inquiline Food Web
Authors: Ellison Aaron M. , Gotelli Nicholas J. , Błędzki Leszek A. , Butler Jessica L.
Published: May 2020

Abstract

Phytotelmata, the water-filled habitats in pitcher plants, bromeliad tanks, and tree-holes, host multitrophic food webs that are model experimental systems for studying food-web structure and dynamics. However, the plant usually is considered simply as an inert container, not as an interacting part of the food web. We used a manipulative field experiment with a response-surface design to determine effects of nutrient enrichment (multiple levels of NH4NO3, PO4, and captured prey), top predator (removed or present), and the plant itself (with or without plastic tubes inserted into the pitchers to isolate the food web from the plant) on the macrobial food web within the modified leaves (“pitchers”) of the carnivorous pitcher plantSarracenia purpurea. Connection to the plant, addition of NH4NO3and removal of the top predator significantly increased the food web’s saturation, defined as its trophic depth and number of interactions. No effects on food-web saturation resulted from addition of PO4or supplemental prey. Plants such asS. purpureathat create phytotelmata are more than inert containers and their inhabitants are more than commensal inquilines. Rather, both the plant and the inquilines are partners in a complex network of interactions.
Substrate Resistance to Traction Forces Controls Fibroblast Polarization
Authors: Missirlis D. , Haraszti T. , Heckmann L. , Spatz J. P.
Published: May 2020

The mechanics of fibronectin-rich extracellular matrix regulate cell physiology in a number of diseases, prompting efforts to elucidate cell mechanosensing mechanisms at the molecular and cellular scale. Here, the use of fibronectin-functionalized silicone elastomers that exhibit considerable frequency-dependence in viscoelastic properties unveiled the presence of two cellular processes that respond discreetly to substrate mechanical properties. Soft elastomers supported efficient focal adhesion maturation and fibroblast spreading due to an apparent stiff surface layer. However, soft elastomers did not enable cytoskeletal and fibroblast polarization; elastomers with high cross-linking and low deformability were required for polarization. The underlying reason for this behavior was the inability of soft elastomeric substrates to resist traction forces, rather than a lack of sufficient traction force generation; accordingly, mild inhibition of actomyosin contractility rescued fibroblast polarization even on the softer elastomers. Our findings help reconcile previously proposed local and global models of cell mechanosensing by demonstrating the differential dependence of substrate mechanics on distinct cellular processes.

Statement of Significance

The mechanisms cells employ to sense and respond to the mechanical properties of their surroundings remain incompletely understood. In this study we used a commercial silicone elastomer formulation to prepare compliant, fibronectin-coated substrates and investigate the adhesion and polarization of human fibroblasts. Our results suggest the existence of at least two discrete mechanosensing processes regulated at different time and length (force) scales. Focal adhesion assembly and cell spreading were promoted by a stiff surface layer independent from bulk viscoelasticity, whereas effective cell polarization required elevated elastomer stiffness, sufficient to resist applied cell traction. The results presented here have implications on the use of elastomeric substrates as biomaterials for mechanosensing studies or clinical applications.
Yeast-Expressed SARS-CoV Recombinant Receptor-Binding Domain (RBD219-N1) Formulated with Aluminum Hydroxide Induces Protective Immunity and Reduces Immune Enhancement
Authors: Chen Wen-Hsiang , Tao Xinrong , Agrawal Anurodh , Algaissi Abdullah , Peng Bi-Hung , Pollet Jeroen , Strych Ulrich , Bottazzi Maria Elena , Hotez Peter J. , Lustigman Sara , Du Lanying , Jiang Shibo , Tseng Chien-Te K.
Published: May 2020

We developed a severe acute respiratory syndrome (SARS) subunit recombinant protein vaccine candidate based on a high-yielding, yeast-engineered, receptor-binding domain (RBD219-N1) of the SARS beta-coronavirus (SARS-CoV) spike (S) protein. When formulated with Alhydrogel®, RBD219-N1 induced high-level neutralizing antibodies against both pseudotyped virus and a clinical (mouse-adapted) isolate of SARS-CoV. Here, we report that mice immunized with RBD219-N1/Alhydrogel® were fully protected from lethal SARS-CoV challenge (0% mortality), compared to ∼ 30% mortality in mice when immunized with the SARS S protein formulated with Alhydrogel®, and 100% mortality in negative controls. An RBD219-N1 formulation Alhydrogel® was also superior to the S protein, unadjuvanted RBD, and AddaVax (MF59-like adjuvant)-formulated RBD in inducing specific antibodies and preventing cellular infiltrates in the lungs upon SARS-CoV challenge. Specifically, a formulation with a 1:25 ratio of RBD219-N1 to Alhydrogel® provided high neutralizing antibody titers, 100% protection with non-detectable viral loads with minimal or no eosinophilic pulmonary infiltrates. As a result, this vaccine formulation is under consideration for further development against SARS-CoV and potentially other emerging and re-emerging beta-CoVs such as SARS-CoV-2.
Optical control of ERK and AKT signaling promotes axon regeneration and functional recovery of PNS and CNS inDrosophila
Authors: Wang Qin , Fan Huaxun , Li Feng , Skeeters Savanna S. , Krishnamurthy Vishnu , Song Yuanquan , Zhang Kai
Published: May 2020

Neuroregeneration is a dynamic process synergizing the functional outcomes of multiple signaling circuits. Channelrhodopsin-based optogenetics shows feasibility of stimulating neural repair but does not pin down specific signaling cascades. Here, we utilized optogenetic systems, optoRaf and optoAKT, to delineate the contribution of the ERK and AKT signaling pathways to neuroregeneration in liveDrosophilalarvae. We showed that optoRaf or optoAKT activation not only enhanced axon regeneration in both regeneration competent and incompetent sensory neurons in the peripheral nervous system, but also allowed temporal tuning and proper guidance of axon regrowth. Furthermore, optoRaf and optoAKT differ in their signaling kinetics during regeneration, showing a gated versus graded response, respectively. Importantly in the central nervous system, their activation promotes axon regrowth and functional recovery of the thermonociceptive behavior. We conclude that non-neuronal optogenetics target damaged neurons and signaling subcircuits, providing a novel strategy in the intervention of neural damage with improved precision.
Evolutionary Changes in Left-Right Visceral Asymmetry inAstyanaxCavefish
Authors: Ma Li , Ng Mandy , Shi Janet , Gore Aniket V. , Castranova Daniel , Weinstein Brant M. , Jeffery William R.
Published: May 2020

Vertebrates show conserved left-right (L-R) asymmetry of internal organs controlled by Nodal-Pitx2/Lefty signaling [1-3]. Modifications in L-R asymmetry occur in mutants [4] and rarely in humans [5], but little is known about natural L-R changes during evolution. Here we describe changes in L-R asymmetry inAstyanax mexicanus, a teleost with ancestral surface (surface fish) and derived cave (cavefish) morphs [6]. In teleosts, Nodal-Pitx2 signaling is activated in the left lateral plate mesoderm (LPM), the cardiac tube jogs to the left and loops to the right (D-looping), and the liver and pancreas form on opposite sides of the midline. Surface fish show conventional L-R patterning, but cavefish can show Nodal-Pitx2 expression in the right LPM or bilaterally, left (L)-looping hearts, and reversed liver and pancreas asymmetry, and these reversals have no effect on survival. The Lefty1 Nodal antagonist is expressed along the surface fish and cavefish midlines, but expression of the Lefty2 antagonist is absent in the LPM of most cavefish embryos, suggesting a role forlefty2(lft2) in changing organ asymmetry. Although CRISPR-Cas9lft2editing affected D-looping in surface fish, the cavefishlft2gene showed no coding mutations, and was expressed normally during cavefish gastrulation, suggesting downregulation by regulatory changes. Reciprocal hybridization, the fertilization of cavefish eggs with surface fish sperm andvice versa, indicated that the change in cavefish L-R asymmetry is a maternal genetic effect. Our studies reveal natural changes in internal organ asymmetry during evolution and introduceA. mexicanusas a new model to study the underlying mechanisms.
BioVizConnect: Web application linking CyVerse cloud resources to genomic visualization in the Integrated Genome Browser
Authors: Raveendran Karthik , Freese Nowlan H , Kintali Chaitanya , Tiwari Srishti , Bole Pawan , Dias Chester , Loraine Ann E
Published: May 2020

Genomics researchers do better work when they can interactively explore and visualize data. However, due to the vast size of experimental datasets, researchers are increasingly using powerful, cloud-based systems to process and analyze data. These remote systems, called science gateways, offer user-friendly, Web-based access to high performance computing and storage resources, but typically lack interactive visualization capability. In this paper, we present BioVizConnect, a middleware Web application that links the CyVerse science gateway to the Integrated Genome Browser (IGB), a highly interactive native application implemented in Java that runs on the user’s personal computer. Using BioVizConnect, users can (i) stream data from the CyVerse data store into IGB for visualization, (ii) improve the IGB user experience for themselves and others by adding IGB specific metadata to CyVerse data files, including genome version and track appearance, and (iii) run compute-intensive visual analytics functions on CyVerse infrastructure to create new datasets for visualization in IGB or other applications. To demonstrate how BioVizConnectfacilitates interactive data visualization, we describe an example RNA-Seq data analysis investigating how heat and desiccation stresses affect gene expression in the model plantArabidopsis thaliana. Lastly, we discuss limitations of the technologies used and suggest opportunities for future work. BioVizConnectis available fromhttps://bioviz.org.
The architecture of EMC reveals a path for membrane protein insertion
Authors: O’Donnell John P. , Phillips Ben P. , Yagita Yuichi , Juszkiewicz Szymon , Wagner Armin , Malinverni Duccio , Keenan Robert J. , Miller Elizabeth A. , Hegde Ramanujan S.
Published: May 2020

Approximately 25% of eukaryotic genes code for integral membrane proteins that are assembled at the endoplasmic reticulum. An abundant and widely conserved multi-protein complex termed EMC has been implicated in membrane protein biogenesis, but its mechanism of action is poorly understood. Here, we define the composition and architecture of human EMC using biochemical assays, crystallography of individual subunits, site-specific photocrosslinking, and cryo-EM reconstruction. Our results show that EMC’s cytosolic domain contains a large, moderately hydrophobic vestibule that binds a substrate’s transmembrane domain (TMD). The cytosolic vestibule leads into a lumenally-sealed, lipid-exposed intramembrane groove large enough to accommodate a single substrate TMD. A gap between the cytosolic vestibule and intramembrane groove provides a path for substrate egress from EMC. These findings suggest how EMC facilitates energy-independent membrane insertion of TMDs, explain why only short lumenal domains are translocated by EMC, and constrain models of EMC’s proposed chaperone function.
Spinal motoneurones are intrinsically more responsive in the adult G93A SOD1 mouse model of Amyotrophic Lateral Sclerosis
Authors: Jensen D.B. , Kadlecova M. , Allodi I. , Meehan C.F.
Published: May 2020

In vitrostudies from transgenic Amyotrophic Lateral Sclerosis models have suggested an increased excitability of spinal motoneurones. However,in vivointracellular recordings from adult ALS mice models have produced conflicting findings. Previous publications using barbiturate anaesthetised G93A SOD1 mice suggested that some motoneurones are hypo-excitable, defined by deficits in repetitive firing. Our own previous recordings in G127X SOD1 mice using different anaesthesia, however, showed no repetitive firing deficits, and increased persistent inward currents at symptom onset. These discrepancies may be due to differences between models, symptomatic stage, anaesthesia or technical differences. To investigate this, we repeated our original experiments, but in adult male G93A mice at both presymptomatic and symptomatic stages, under barbiturate anaesthesia.

In vivointracellular recordings from antidromically identified spinal motoneurones revealed no significant differences in the ability to fire repetitively in the G93A SOD1 mice. Motoneurones in G93A SOD1 mice fired significantly more spontaneous action potentials. Rheobase was significantly lower and the input resistance and input-output gain were significantly higher in both presymptomatic and symptomatic G93A SOD1 mice. This was despite a significant increase in the duration of the post-spike after-hyperpolarisation (AHP) in both presymptomatic and symptomatic G93A SOD1 mice. Finally, evidence of increased activation of persistent inward currents was seen in both presymptomatic and symptomatic G93A SOD1 mice. Our results do not confirm previous reports of hypo-excitability of spinal motoneurones in the G93A SOD1 mouse and demonstrate that the motoneurones do in fact show an increased response to inputs.

Key Point Summary

Althoughin vitrorecordings using neonatal preparations from mouse models of Amyotrophic Lateral Sclerosis (ALS) suggest increased motoneurone excitability,in vivorecordings in adult ALS mouse models have been conflicting.

In adult G93A SOD1 models, spinal motoneurones have previously been shown to have deficits in repetitive firing, in contrast to the G127X SOD1 mouse model.

Ourin vivointracellular recordings in barbiturate-anaesthetised adult male G93A SOD1 mice reveal no deficits in repetitive firing either prior to or after symptom onset.

We show that deficits in repetitive firing ability can be a consequence of experimental protocol and should not be used alone to classify otherwise normal motoneurones as hypo-excitable.

Motoneurones in the G93A SOD1 mice showed an increased response to inputs, with lower rheobase, higher input-output gains and increased activation of persistent inward currents.
Productivity or illusion? Assessing employees' behavior in an employability paradox
Authors: Imam Hassan , Chambel Maria José
Published: May 2020

Purpose

Employability has been studied in different disciplines (e.g. occupational health and career) and has been seen as a personal resource with overall positive outcomes. The present research investigates the behavioral implications of (perceived) employability and responds to the recent call of research that perceived employability could have not only positive but also negative behavioral implications. Furthermore, this study aims to reduce the asymmetry of data set and replication of existing results in non-Western economies.

Design/methodology/approach

Multinationals were taken as context to test the hypotheses, and a sample of 230 white-collar employees was drawn from fast-moving consumer goods companies. Partial least square–structural equation modeling through SmartPLS was used to analyze the data.

Findings

In light of social exchange theory, the present research identified the dark side of employability, which may impair the employer–employee relationship. Perceived employability did not relate significantly with in-role performance, nor did it correlate with organizational citizenship behavior, that is, a discretionary behavior promotes the efficient and effective functioning. However, perceived employability had a positive significant relationship with OCBI, that is, helping supervisors and coworkers with heavy workloads, as well as with counterproductive behaviors.

Practical implications

Employable workers have always been considered key players and an asset for organizations due to their high productivity skills. A balanced employer–employee relationship creates a mutual win; therefore, a carefully drafted human resources policy may help organizations to fulfill the needs of employable workers and reap optimal benefits in terms of productivity. Behavioral training to supervisors/managers may help to assertively deal with employees' negative behavior without further escalation.

Originality/value

The present study suggests a paradoxical perspective in employability – a behavior debate, which is in an initial phase where it is difficult to determine whether employable workers are productive to the organizations or not.
Malaria classroom corner: a school-based intervention to promote basic malaria awareness and common control practices among school-age children
Authors: Chukwuocha Uchechukwu M. , Iwuoha Greg N. , Ogara Chisom M. , Dozie Ikechukwu N.S.
Published: May 2020

Purpose

This study assessed the effectiveness of malaria classroom corner (MCC), school-based intervention in the promotion of basic malaria awareness and common control practices among children of primary school age.

Design/methodology/approach

A quasi-experimental design was employed, involving 206 children of primary 5 and 6 classes from two randomly selected public primary schools in Owerri, South Eastern Nigeria. The MCC was designed and set up in the intervention school (with 103 children) while the control school (with 103 children) was offered malaria health talk. Structured pre-tested questionnaire was used to collect data pre- and post-intervention in both schools. Data was analysed using Statistical Package – Stata version 14.1 (Stata Corp, College Station, TX, USA).

Findings

Results show that there was a significant enhancement of basic malaria awareness (p = 0.0003) and common preventive and management practices (p = 0.0202) among children in the intervention primary school compared to those in the control primary school.

Research limitations/implications

The study did not account for actual behaviour change, as its scope was within basic malaria awareness and common control practices.

Practical implications

This approach could enhance awareness and proactiveness of school children towards malaria prevention and overall health consciousness.

Social implications

This could help in achieving a healthy population of school children with a positive effect on their school performance.

Originality/value

The MCC could provide a simple, participatory and effective approach for the promotion of basic malaria awareness and common control practices among primary school-age children in malaria endemic areas. Such children could, in turn, become malaria conversation drivers and behaviour change agents in their homes and communities, thereby contributing to the malaria elimination efforts.
The role of project management in threatened species recovery
Authors: Willemsen Madelon , Pollack Julien , Algeo Chivonne
Published: May 2020

Purpose

There are significant, ongoing threats of species extinction. Threatened species recovery programs are an important way of reducing this threat, but many recovery programs are unsuccessful. The purpose of this paper is to explore the issues facing species recovery programs, and the potential benefits to be found in managing threatened species recovery from a project management perspective.

Design/methodology/approach

This research used the Grounded Theory Method to analyze the contents of four senate inquiries and 21 interviews with recovery experts. The Grounded Theory Method was then used to inductively develop concepts and theories that explain some of the issues faced in the delivery of recovery programs in Australia. These were explored from a project management perspective, to understand ways that project management could provide benefit to the recovery planning process.

Findings

Eight core challenges that have an impact on recovery emerged from the data. It was identified that there is a general lack of integration of project management into the recovery process. This was found to be particularly evident in terms of the recovery project lifecycle, risk management and stakeholder management. Strategies for addressing these issues are discussed.

Originality/value

Conservation scientists typically focus on technical recovery competencies. The authors argue that managing recovery from a project management perspective will increase recovery success rates through an increased focus on the contextual and behavioral competencies that are essential to the management and delivery of recovery projects and programs.
Informal repatriate knowledge transfer: a qualitative analysis of Malaysian corporate executives
Authors: Amir Sabrina , Okimoto Tyler G. , Moeller Miriam
Published: May 2020

Purpose

This paper examines how informal knowledge transfer processes unfold during the repatriation of Malaysian executives. The goal is to develop a repatriate knowledge transfer process model, explaining the informal process through which repatriates make decisions about and transfer newly acquired knowledge.

Design/methodology/approach

Given the unexplored nature of the informal knowledge transfer process the study investigates, this research adopts an exploratory qualitative research approach using interview data from 10 Malaysian corporate executives over a period of 14 months, covering prerepatriation and postrepatriation stages.

Findings

The findings indicate that from the repatriates' perspectives, the process flows during repatriates' knowledge transfer depend on the ability and motivation of repatriates, as well as their opportunity to communicate the newly acquired knowledge to their home country organization. We likewise learned that the repatriates' ability to overcome repatriate adjustment and knowledge transfer challenges is crucial in order for them to proactively initiate informal knowledge transfer.

Practical implications

This research is significant as it will assist current and future expatriates to plan and prepare for repatriation and eventual knowledge transfer. The findings will also be useful to organizations that employ repatriates in preparing action plans for repatriation rather than solely focusing on expatriation.

Originality/value

Research and practice formally argue that expatriates are expected to transfer knowledge from the home country organization to the host country organization. While on assignment, expatriates become exposed to various types of new knowledge during the assignment, setting them up to disseminate this newly acquired knowledge to their home country organization upon repatriation – however, knowledge transfer upon repatriation is largely informal. This paper examines how this informal knowledge transfer process unfolds in the repatriation context over a period of 14 months by qualitatively tracing the experiences of 10 Malaysian corporate executives.
Combined serum carcinoembryonic antigen and cytokeratin 19 fragment levels provide a sensitive biomarker for lymph node metastasis in extramammary Paget’s disease
Authors: Kato Hiroshi , Nakamura Motoki , Watanabe Shoichi , Oda Takao , Morita Akimichi
Published: May 2020

Most cases of extramammary Paget’s disease are diagnosed at an early stage. For advanced cases, few effective treatments are available and the prognosis is poor. Therefore, developing sensitive biomarkers for metastatic cases is a critical challenge. Carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are two potentially useful biomarkers. In the present retrospective large‐scale study, we identified other potential biomarkers of lymph node metastasis. Patients with extramammary Paget’s disease who visited our dermatology clinic between April 2004 and March 2019 (n = 138; mean age, 73.4 years; 85 men and 53 women) were enrolled in the study. The patients were divided into three groups according to the presence of regional lymph node metastasis and distant metastasis to evaluate the relationship between metastasis and various tumor markers: serum CEA, carbohydrate antigen (CA)19‐9, CA125, CA15‐3 and CYFRA. For distal metastasis, each biomarker had high sensitivity and specificity. The sensitivities and specificities for regional lymph node metastasis were as follows: CEA, 50.0% and 88.6%; CA19‐9, 50% and 89.5%; CA125, 0% and 98.2%; CA15‐3, 0% and 96.0%; and CYFRA, 66.7% and 95.0%, respectively. We also analyzed biomarker combinations. The sensitivity and specificity of the combination of all five biomarkers (CEA, CA19‐9, CA125, CA15‐3 and CYFRA) were 83.3% and 70.9%, respectively. The sensitivity of the combination of just CEA and CYFRA was also 83.3%. Screening for combinations of these biomarkers will facilitate the detection of early lymph node metastasis in patients with extramammary Paget’s disease.
Plant community flood resilience in intensively managed grasslands and the role of the plant economic spectrum
Authors: Oram Natalie J. , De Deyn Gerlinde B. , Bodelier Paul L. E. , Cornelissen Johannes H. C. , van Groenigen Jan Willem , Abalos Diego
Published: May 2020

The increasing frequency of extreme weather events, such as floods, requires management strategies that promote resilience of grassland productivity. Mixtures of plant species may better resist and recover from flooding than monocultures, as they could combine species with stress‐coping and resource acquisition traits. This has not yet been tested in intensively managed grasslands despite its relevance for enhancing agroecosystem resilience.

Using intact soil cores from an 18‐month‐old field experiment, we tested how 11 plant communities (Festuca arundinacea, Lolium perenne, Poa trivialis and Trifolium repens in monoculture, two‐ and four‐species mixtures) resist and recover from repeated flooding in a 4‐month greenhouse experiment.

We found that plant community composition, not whether the community was a mixture or monoculture, influenced the community's resistance to flooding, although most communities were able to resist and recover from both floods.

The plant community's position on the leaf economic spectrum in flooded conditions was related to its resistance to and recovery from flooding. Resistance to and recovery from a severe flood were related to flood‐induced intraspecific trait variation, causing a shift in the community's position on the leaf resource economic spectrum. In flooded conditions, resource‐conservative communities (characterized by low specific leaf area, low leaf nitrogen content and high leaf dry matter content) better resisted and recovered from flooding. The community's position on the root resource economic spectrum was less connected to the community's resistance and recovery.

Synthesis and applications. Our study shows that in flooded conditions, resource‐conservative plant communities are more resilient to flooding than resource‐acquisitive communities in an intensively managed grassland. This suggests that plant community position on the leaf economic spectrum, as well as species’ flood‐induced intraspecific variation, should be considered when designing grasslands to withstand increasing flood frequency and severity.
Estimates of beta cell function adjusted by anthropometric markers in patients with T2DM
Authors: Zhang Mingchen , Su Yinxia , Quan Li , Jiang Sheng , Yao Hua
Published: May 2020

We sought to determine whether adjusting the indices used to assess beta cell function by anthropometric markers of obesity improves their clinical value in a diabetic population. We conducted a cross‐sectional survey of 3732 diabetic patients who underwent a 100 g carbohydrate meal test. Insulin secretion was estimated using HOMA‐B of steady state as well as △C0‐30/△G0‐30, △AUCc30‐120/△AUCG30‐120 and CPIn for dynamic state. Body weight index, waist circumference, waist‐hip ratio and body surface area were recorded. The final analysis included 2873 T2DM patients. Correlation analyses showed that there was a poor correlation between diabetic duration and CPI30 (r = −.040, P < .05), and there were no remarkable changes in the correlation coefficient after CPI30 was divided by BMI, WC, WHR, or body surface area, respectively. The same was found for the correlation between HbA1c and CPI120 with these measures. The main determinants of diabetic duration were age (β = 0.388, P < .001), log HOMA‐IR (β = −0.328, P < .001), CPI30 (β = −0.045, P = .011). There were no remarkable changes in β weights between diabetic duration and CPI30 when it was corrected with anthropometric markers in the multiple stepwise linear regression analyses. The same was found between HbA1c and CPI120. CPI30 and CPI120 are more practical indexes. Correcting the indices used to estimate the beta cell function by anthropometric markers of obesity may not improve their correlations with diabetic duration or HbA1c in a diabetic population.
Kogan v Martin: A New Framework for Joint Authorship in Copyright Law
Authors: Simone Daniela
Published: May 2020

The Court of Appeal has set out a new framework for the application of copyright law's joint authorship test in a recent landmark case. Kogan v Martin brings some welcome clarity to the complex joint authorship landscape, embedding an inclusive pro‐collaboration default standard. This case note contrasts the appeal court's nuanced framing of the dispute with the first instance court's narrower approach. The note then examines the new joint authorship framework and explains how it allows the test to be applied with an eye to the reality of collaborative creative endeavours. Finally, the significance of Kogan v Martin is highlighted, as are some questions which remain unanswered.
Metachronous primary lung adenocarcinomas harboring distinct KRAS mutations
Authors: Hu Yan , Ren Siying , Chen Chen , Liang Qingchun , Yu Fenglei , Liu Wenliang
Published: May 2020

To distinguish whether multiple lung nodules represent multiple primary lung cancers (MPLC) or intrapulmonary metastases (IPM) is crucial for staging and subsequent therapy. We herein present the first report of a patient with two simultaneously resected metachronous lung adenocarcinomas in the right upper lobe, each with a distinct driver mutation in the KRAS gene identified by targeted next generation sequencing (NGS). The nodules appeared chronologically metachronous, with a 3.7 year interval. Histopathology showed two histologically identical adenocarcinomas, without lymph node metastases. It was hard to decide whether they should be classified as either MPLC or IPM based only on the clinicopathological criteria. Sequencing further revealed distinct KRAS mutation in each tumor, with one tumor harboring the KRAS‐G12C mutation, and the other tumor harboring the KRAS‐Q61H mutation. Incorporation of the molecular data cleared the confusion with regard to staging and spared this patient from adjuvant therapy. This case highlights that molecular profiling allows for better differentiation between MPLC and IPM than histopathology alone.

Key points

To the best of our knowledge, this is the first case of multiple primary lung cancers harboring distinct KRAS mutations.

The case highlights the importance of incorporating molecular profiling using NGS along with the clinicopathological criteria in classifying multiple lung tumors.
Mooring scientific instruments on the seabed—Design, deployment protocol and performance of a recoverable frame for acoustic receivers
Authors: Goossens Jolien , T'Jampens Michiel , Deneudt Klaas , Reubens Jan
Published: May 2020

Acoustic telemetry is increasingly used to observe and monitor animal movements in aquatic environments. Practical deployment mechanisms are needed to sustain consistent data flows in challenging environments.

A tripod frame was developed to facilitate the deployment of acoustic receivers on the seabed, allowing for the recovery of all equipment with an acoustic release system.

The procedures of deployment and recovery proved to be practical and efficient during a field trial in the North Sea. Compared to a common cabled design, the tripod frame realized a significantly higher detection probability and performed consistently better at greater distance and louder ambient noise.

In the context of ocean observation in challenging environments, the tripod frame is a useful tool for temporary and continuous monitoring of tagged fish presence, potentially fitted with additional instruments.
Habitat fragmentation affects movement and space use of a specialist folivore, the koala
Authors: Rus A. I. , McArthur C. , Mella V. S. A. , Crowther M. S.
Published: May 2020

Habitat fragmentation changes landscape patterns and can disrupt many important ecological processes. Movement allows individuals to find resource patches to maintain their fitness and habitat fragmentation can disrupt this process. We explored the ecological impact of habitat fragmentation on movement and space use of a specialist folivore, the koala Phascolarctos cinereus. We GPS tracked koala movements within a fragmented agricultural landscape. We calculated the total distance moved across four months and the number of core patches by each koala. We used four metrics (proximity, functional connectivity, clumpiness, perimeter‐to‐area fractal dimension) to quantify landscape fragmentation within koala home ranges and determine its effects on movement and space use. Functional connectivity had the greatest effect on individual movement and space use. Decreasing connectivity led to longer and more direct movements by koalas and more core patches within an individual home range. Our study provides insight into the effects of habitat fragmentation on animal movement and space use, which can be used by wildlife managers to plan and manage landscapes more effectively. We conclude that restoring or protecting resource patches to promote greater functional connectivity will reduce the costs associated with the isolation of resource patches for species occupying fragmented landscapes. By providing a quantitative relationship between habitat connectivity and movement and space use costs, our results enable managers to set restoration targets, by identifying the most effective way to provide the functional connectivity minimizing the negative impact on focal species.
Human disturbance and prey occupancy as predictors of carnivore richness and biomass in a Himalayan hotspot
Authors: Li X. Y. , Bleisch W. V. , Liu X. W. , Hu W. Q. , Jiang X. L.
Published: May 2020

Carnivores are of high ecological importance and often serve as flagship species for conservation. Yet, the direct and indirect effects of trophic interactions and human disturbance on carnivore communities and the occurrence of their prey in temperate forests remain poorly understood. Here we evaluate the direct and indirect effects of net primary productivity, prey (Muntjac spp) occupancy and human disturbance in shaping carnivore richness and biomass based on camera‐trap data and path analysis. Path analysis indicated that muntjac occupancy and proximity of human settlements were the main factors structuring carnivore communities. Carnivore biomass was directly affected by muntjac occupancy, while carnivore richness increased with distance from the nearest residential site. Muntjac occupancy per se directly depended on net primary productivity. We also identified several indirect effects on carnivore biomass. Increasing distance to the nearest residential site had a positive indirect effect on carnivore biomass that was mediated by increasing carnivore richness. Net primary productivity was positively associated with carnivore biomass indirectly via increasing muntjac occupancy. There were no significant correlations between the occurrence probability of livestock and muntjac. Our results point to the importance of incorporating prey occurrence and human disturbance in modelling biodiversity patterns of carnivore communities. Carnivore conservation management practices should include efforts to stop hunting and to restrict human presence in the core zones of protected areas.