bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrinsic Timescales Across the Basal Ganglia
Authors: Nougaret Simon , Fascianelli Valeria , Ravel Sabrina , Genovesio Aldo
Published: April 2021

Recent studies have shown that neuronal stability over time can be estimated by the structure of the spike-count autocorrelation of neuronal populations. This estimation, called the intrinsic timescale, has been computed for several cortical areas and can be used to propose a cortical hierarchy reflecting a scale of temporal receptive windows between areas. In this study, we performed an autocorrelation analysis on neuronal populations of three basal ganglia (BG) nuclei, including the striatum and the subthalamic nucleus (STN), the input structures of the BG, and the external globus pallidus (GPe). The analysis was performed during the baseline period of a motivational visuomotor task in which monkeys had to apply different amounts of force to receive a different amount of reward. We found that the striatum and the STN have longer intrinsic timescales than the GPe. Moreover, our results allow for the placement of these subcortical structures within the already-defined scale of cortical temporal receptive windows. Estimates of intrinsic timescales are important in adding further constraints in the development of computational models of the complex dynamics among these nuclei and throughout cortico-BG-thalamo-cortical loops.
Selective abrogation of S6K2 maps lipid homeostasis as a survival vulnerability in MAPKi-resistant NRASMUTmelanoma
Authors: Lipchick Brittany , Guterres Adam N. , Chen Hsin-Yi , Zundell Delaine M. , Aguila Segundo Del , Reyes-Uribe Patricia I. , Basu Subhasree , Yin Xiangfan , Kossenkov Andrew V. , Lu Yiling , Mills Gordon B. , Liu Qin , Goldman Aaron R. , Murphy Maureen E. , Speicher David W. , Villanueva Jessie
Published: April 2021

Although oncogenic NRAS activates MAPK signaling, inhibition of the MAPK pathway is not therapeutically efficacious in NRAS-mutant tumors. Here we report that silencing the ribosomal protein S6 kinase 2 (S6K2), while preserving the activity of S6K1, perturbs lipid metabolism, enhances fatty acid unsaturation, and triggers lethal lipid peroxidation selectively in NRAS-mutant melanoma cells that are resistant to MAPK inhibition. S6K2 depletion induces ER stress, and PPARα activation, triggering cell death selectively in MAPKi-resistant melanoma. We show that combining PPARα agonists and polyunsaturated fatty acids phenocopies the effects of S6K2 abrogation, blocking tumor growth in PDX and immunocompetent mouse pre-clinical models. Collectively, our study establishes S6K2 and its effector subnetwork as promising targets for NRAS-mutant melanoma that are resistant to global MAPK pathway inhibitors.

One Sentence Summary

S6K2 is a vulnerability in MAPK inhibitor-resistant NRAS-mutant melanoma
Within-host genetic micro-diversity ofMycobacterium tuberculosisand the link with tuberculosis disease features
Authors: Genestet Charlotte , Hodille Elisabeth , Massol François , Refrégier Guislaine , Barbry Alexia , Westeel Emilie , Lina Gérard , Ader Florence , Jacob Laurent , Dray Stéphane , Berland Jean-Luc , Venner Samuel , Dumitrescu Oana
Published: April 2021

Tuberculosis (TB), caused byMycobacterium tuberculosis(Mtb) complex, is still the number one deadly contagious disease. Mtb infection results in a wide spectrum of clinical presentations and severity symptoms, but without proven Mtb genetic determinants. Thanks to a collection of 355 clinical isolates with associated patient’s clinical data, we showed that Mtb micro-diversity within patient isolates is strongly correlated with TB-associated severity scores. Interestingly, this diversity is driven by a selection pressure to adapt to different lifestyles related to the infection site. Taken together, these results provide a new insight to better understand TB pathophysiology. Furthermore, Mtb micro-diversity could be envisioned as a new prognostic tool to improve the management of TB patients.
Dissociation of early and late face-related processes in Autism Spectrum Disorder and Williams syndrome
Authors: Gomez Alice , Lio Guillaume , Costa Manuela , Sirigu Angela , Demily Caroline
Published: April 2021

Williams syndrome (WS) and Autism Spectrum Disorders (ASD) are psychiatric conditions associated with atypical but opposite face-to-face interactions patterns: WS patients overly stare at others, ASD individuals escape eye contact. Whether these behaviors result from dissociable visual processes within the occipito-temporal pathways is unknown.

Using high-density electroencephalography, multivariate signal processing algorithms and a protocol designed to identify and extract evoked activities sensitive to facial cues, we investigated how WS (N=14), ASD (N=14) and neurotypical subjects (N=14) decode the information content of a face stimulus.

We found two neural components in neurotypical participants, both strongest when the eye region was projected onto the subject’s fovea, simulating a direct eye contact situation, and weakest over more distant regions, reaching a minimum when the focused region was outside the stimulus face. The first component peaks at 170ms, an early signal known to be implicated in low-level face features. The second is identified later, 260ms post-stimulus onset and is implicated in decoding salient face social cues.

Remarkably, both components were found distinctly impaired and preserved in WS and ASD. In WS, we could weakly decode the 170ms signal based on our regressor relative to facial features, probably due to their relatively poor ability to process faces’ morphology, while the late 260ms component was highly significant. The reverse pattern was observed in ASD participants who showed neurotypical like early 170ms evoked activity but impaired late evoked 260ms signal. Our study reveals a dissociation between WS and ASD patients and point at different neural origins for their social impairments.
Whole genome sequencing revealed genetic diversity and selection of Guangxi indigenous chickens
Authors: Sun Junli , Chen Tao , Zhu Min , Wang Ran , Huang Yingfei , Wei Qiang , Yang Manman , Liao Yuying
Published: April 2021

Guangxi chickens play an important role in promoting the high-quality development of the broiler industry in China, but their value and potential are yet to be discovered. To determine the genetic diversity and population structure of Guangxi indigenous chicken, we analyzed the whole genomes of 185 chicken from 8 phenotypically and geographically representative Guangxi chicken breeds, together with 12 RJFt, 12 BRA and 12 WL genomes available from previous studies. Calculation of heterozygosity (Hp), nucleotide diversity (π), and LD level indicated that Guangxi populations were characterized by higher genetic diversity and lower differentiation than RJFt and commercial breeds except HGFC. Population structure analysis also confirmed the introgression from commercial broiler breeds. Each population clustered together while the overall differentiation was small, MA has the richest genetic diversity among all varieties. Selective sweep analysis revealedBCO2,EDN3and other candidate genes have received strong selection in local breeds, these also provided novel breeding visual and data basis for future breeding.
Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp14/nsp10 Exoribonuclease
Authors: Canal Berta , McClure Allison W. , Curran Joseph F. , Wu Mary , Ulferts Rachel , Weissmann Florian , Zeng Jingkun , Bertolin Agustina P. , Milligan Jennifer C. , Basu Souradeep , Drury Lucy S. , Deegan Tom , Fujisawa Ryo , Roberts Emma L. , Basier Clovis , Labib Karim , Beale Rupert , Howell Michael , Diffley John F.X
Published: April 2021

SARS-CoV-2 is a coronavirus that emerged in 2019 and rapidly spread across the world causing a deadly pandemic with tremendous social and economic costs. Healthcare systems worldwide are under great pressure, and there is urgent need for effective antiviral treatments. The only currently approved antiviral treatment for COVID-19 is remdesivir, an inhibitor of viral genome replication. SARS-CoV-2 proliferation relies on the enzymatic activities of the non-structural proteins (nsp), which makes them interesting targets for the development of new antiviral treatments. With the aim to identify novel SARS-CoV-2 antivirals, we have purified the exoribonuclease/methyltransferase (nsp14) and its cofactor (nsp10) and developed biochemical assays compatible with high-throughput approaches to screen for exoribonuclease inhibitors. We have screened a library of over 5000 commercial compounds and identified patulin and aurintricarboxylic acid (ATA) as inhibitors of nsp14 exoribonucleasein vitro. We found that patulin and ATA inhibit replication of SARS-CoV-2 in a VERO E6 cell-culture model. These two new antiviral compounds will be valuable tools for further coronavirus research as well as potentially contributing to new therapeutic opportunities for COVID-19.
Redetermination of the first unknown protein MicroED structure by high resolution X-ray diffraction
Authors: Xu Hongyi , Zou Xiaodong , Högbom Martin , Lebrette Hugo
Published: April 2021

Microcrystal electron diffraction (MicroED) has the potential to considerably impact the field of structural biology. Indeed, the method can solve atomic structures of a wide range of molecules, beyond the reach of single particle cryo-electron microscopy, exploiting crystals too small for X-ray diffraction (XRD) even using X-ray free-electron lasers. However, until the first unknown protein structure – a R2-like ligand-binding oxidase fromSulfolobus acidocaldarius(SaR2lox) – was recently solved at 3.0 Å resolution, MicroED had only been used to study known protein structures previously obtained by XRD. Here, after adapting sample preparation protocols, the structure of theSaR2lox protein originally solved by MicroED was redetermined by XRD at 2.1 Å resolution. In light of the higher resolution XRD data and taking into account experimental differences of the methods, the quality of the MicroED structure is examined. The analysis demonstrates that MicroED provided an overall accurate model, revealing biologically relevant information specific toSaR2lox, such as the absence of an ether cross-link, but did not allow to detect the presence of a ligand visible by XRD in the protein binding pocket. Furthermore, strengths and weaknesses of MicroED compared to XRD are discussed in the perspective of this real-life protein example. The study provides fundaments to help MicroED become a method of choice for solving novel protein structures.

Synopsis

The first unknown protein structure solved by microcrystal electron diffraction (MicroED) was recently published. The redetermination by X-ray diffraction of this protein structure provides new insights into the strengths and weaknesses of the promising MicroED method.
Discovery of target genes and pathways of blood trait loci using pooled CRISPR screens and single cell RNA sequencing
Authors: Morris John A. , Daniloski Zharko , Domingo Júlia , Barry Timothy , Ziosi Marcello , Glinos Dafni A. , Hao Stephanie , Mimitou Eleni P. , Smibert Peter , Roeder Kathryn , Katsevich Eugene , Lappalainen Tuuli , Sanjana Neville E.
Published: April 2021

The majority of variants associated with complex traits and common diseases identified by genome-wide association studies (GWAS) map to noncoding regions of the genome with unknown regulatory effects incisandtrans. By leveraging biobank-scale GWAS data, massively parallel CRISPR screens and single cell transcriptome sequencing, we discovered target genes of noncoding variants for blood trait loci. The closest gene was often the target gene, but this was not always the case. We also identifiedtrans-effects networks of noncoding variants whencistarget genes encoded transcription factors, such asGFI1BandNFE2. We observed that GFI1Btrans-target genes were enriched for GFI1B binding sites and fine-mapped GWAS variants, and expressed in human bone marrow progenitor cells, suggesting that GFI1B acts as a master regulator of blood traits. This platform will enable massively parallel assays to catalog the target genes of human noncoding variants in bothcisandtrans.
The mitotic spindle mediates nuclear migration through an extremely narrow infection structure of the rice blast fungusMagnaporthe oryzae
Authors: Pfeifer Mariel A. , Khang Chang Hyun
Published: April 2021

The blast fungus,Magnaporthe oryzae, causes severe destruction to rice and other crops worldwide. As the fungus infects rice, it develops unique cellular structures, such as an appressorium and a narrow penetration peg, to permit successful invasion of host rice cells. Fundamental knowledge about these cellular structures and how organelles, such as the nucleus, are positioned within them is still emerging. Previous studies show that a single nucleus becomes highly stretched during movement through the narrow penetration peg in an extreme nuclear migration event. Yet, the mechanism permitting this nuclear migration event remains elusive. Here, we investigate the role of the mitotic spindle in mediating nuclear migration through the penetration peg. We find that disruption of spindle function during nuclear migration through the penetration peg prevents development of invasive hyphae and virulence on rice. Furthermore, regulated expression of conserved kinesin motor proteins, MoKin5 and MoKin14, is essential to form and maintain the spindle, as well as, properly nucleate the primary hypha. Overexpression of MoKin5 leads to formation of aberrant microtubule protrusions, which contributes to formation of nuclear fragments within the appressorium and primary hypha. Conversely, overexpression of MoKin14 causes the spindle to collapse leading to the formation of monopolar spindles. These results establish a mechanistic model towards understanding the intricate subcellular dynamics of extreme nuclear migration through the penetration peg, a critical step in the development of rice blast disease.

Importance

Magnaporthe oryzae, also known as the blast fungus, is a formidable hinderance to global food production, including rice. The destructive fungal pathogen develops highly-specialized cells and structures, such as appressoria and penetration pegs, to permit successful invasion of rice cells. Our understanding ofM. oryzae’sfundamental biology during host cell invasion and colonization is still developing. For instance, it is not yet known how organelles, such as the nucleus, migrate through the narrow penetration peg. Moreover, few previous studies examine the role of motor proteins inM. oryzae.In this study, we determined that the mitotic spindle propels a single nucleus through the penetration peg to permit successful development of fungal hyphae inside the first-invaded rice cell. We also identified two conserved kinesin motor proteins, MoKin5 and MoKin14. Our analyses suggested that MoKin5 and MoKin14 exhibit canonical functions inM. oryzaeduring rice infection. This study addressed long-standing questions in rice blast biology, and our results offer opportunities for future research.
CCNE1 amplification is synthetic-lethal with PKMYT1 kinase inhibition
Authors: Gallo David , Young Jordan T.F. , Fourtounis Jimmy , Martino Giovanni , Álvarez-Quilón Alejandro , Bernier Cynthia , Duffy Nicole M. , Papp Robert , Roulston Anne , Stocco Rino , Szychowski Janek , Veloso Artur , Alam Hunain , Baruah Prasamit S. , Fortin Alexanne Bonneau , Bowlan Julian , Chaudhary Natasha , Desjardins Jessica , Dietrich Evelyne , Fournier Sara , Fugère-Desjardins Chloe , de Rugy Theo Goullet , Leclaire Marie-Eve , Liu Bingcan , Melo Henrique , Nicolas Olivier , Singhania Akul , Szilard Rachel K. , Tkáč Ján , Yin Shou Yun , Morris Stephen J. , Zinda Michael , Gary Marshall C. , Durocher Daniel
Published: April 2021

Amplification of the gene encoding cyclin E (CCNE1) is an oncogenic driver in several malignancies and is associated with chemoresistance and poor prognosis. To uncover therapeutic targets forCCNE1-amplified tumors, we undertook genome-scale CRISPR/Cas9-based synthetic lethality screens in cellular models ofCCNE1amplification. Here, we report that increasingCCNE1dosage engenders a vulnerability to the inhibition of the PKMYT1 kinase, a negative regulator of CDK1. To inhibit PKMYT1, we developed RP-6306, an orally bioavailable and selective inhibitor that shows single-agent activity and durable tumor regressions when combined with gemcitabine in models ofCCNE1-amplification. RP-6306 treatment causes unscheduled activation of CDK1 selectively inCCNE1overexpressing-cells, promoting early mitosis in cells undergoing DNA synthesis.CCNE1overexpression disrupts CDK1 homeostasis at least in part through an early activation of the FOXM1/MYBL2/MuvB-dependent mitotic transcriptional program. We conclude that PKMYT1 inhibition is a promising therapeutic strategy forCCNE1-amplified cancers.
Modulation of endometrial E-Cadherin and N-Cadherin by ovarian steroids and embryonic stimuli
Authors: Tiwari Abhishek , Ashray Nancy , Singh Neha , Sharma Shipra , Modi Deepak
Published: April 2021

The endometrium is a dynamic tissue that undergoes extensive remodelling to attain a receptive state which is further modulated in presence of an embryo for successful initiation of pregnancy. Cadherins are the proteins of junctional complex of which E-cadherin (E-Cad) is crucial for maintaining epithelial cell state and integrity of the epithelial barrier; gain of N-cadherin (N-Cad) in epithelial cells leads to epithelial to mesenchymal transition (EMT). In the present study, we aimed to investigate the expression of E-Cad and N-Cad in the mouse endometrial luminal epithelium and its modulation by estrogen, progesterone and embryonic stimuli. We observed that E-Cad is diffusely expressed in the luminal epithelium of mouse endometrium during the estrus stage and upon estrogen treatment. It is apico-laterally and basolaterally sorted at the diestrus stage and in response to combined treatment of estrogen and progesterone. In 3D spheroids of human endometrial epithelial cells, combined treatment with estrogen and progesterone led to lateral sorting of E-Cad. In the mouse endometrium at the time of embryo implantation, there is loss of E-Cad which was associated with the gain of N-Cad suggestive of EMT in the luminal epithelium. This EMT is possibly driven by embryonic stimuli as treatment with estrogen and progesterone did not lead to gain of N-Cad expression. In conclusion, the present study demonstrates that steroid hormones directly affect E-Cad sorting in the endometrial epithelium.
Label-free tracking and mass measurement of single proteins on lipid bilayers
Authors: Foley Eric D. B. , Kushwah Manish S. , Young Gavin , Kukura Philipp
Published: April 2021

We introduce dynamic mass photometry, a method for label-free imaging, tracking and mass measurement of membrane-associated proteins. Our method enables quantitative studies of their mobility, membrane affinity and interactions at the single molecule level. Application to the membrane remodelling GTPase dynamin1 reveals heterogeneous mixtures of oligomers suggesting that the fundamental building block for oligomerisation is a dimer, challenging current tetramer-centric models. Dynamic mass photometry has the ability to transform our approach to studying biomolecular mechanisms in and on lipid bilayers.
Mass-sensitive particle tracking (MSPT) to elucidate the membrane-associated MinDE reaction cycle
Authors: Heermann Tamara , Steiert Frederik , Ramm Beatrice , Hundt Nikolas , Schwille Petra
Published: April 2021

In spite of their great importance in biology, methods providing access to spontaneous molecular interactions with and on biological membranes have been sparse. So far, it has been consensus that their observation with sufficient sensitivity and time resolution requires the introduction of - predominantly fluorescent-labels to the system. However, the recent advent of mass photometry to quantify mass distributions of unlabelled biomolecules landing on surfaces raised hopes that this approach could be transferred to membranes. Here, we introduce mass-sensitive particle tracking (MSPT), enabling simultaneous label-free tracking and monitoring of molecular masses of single biomolecules diffusing on lipid membranes. We applied this approach to the highly non-linear reaction cycles underlying MinDE protein self-organisation. MSPT allowed us to determine the stoichiometry and turnover of individual membrane-bound MinD/MinDE protein complexes and to quantify their size-dependent diffusion. We found that MinD assembles into complexes larger than the commonly postulated dimer, through lateral interactions of membrane-bound complexes and subunit recruitment from solution. Furthermore, the ATPase-activating protein MinE interconnects MinD into high-molecular-weight heteromeric complexes and affects their subunit turnover and concerted membrane release. This study demonstrates the potential of MSPT to enhance our quantitative understanding of both prokaryotic and eukaryotic membrane-associated biological systems.
Structure-based design of selective salt-inducible kinase (SIK) inhibitors
Authors: Tesch Roberta , Rak Marcel , Raab Monika , Berger Lena M. , Kronenberger Thales , Joerger Andreas C. , Berger Benedict-Tilman , Abdi Ismahan , Hanke Thomas , Poso Antti , Strebhardt Klaus , Sanhaji Mourad , Knapp Stefan
Published: April 2021

Salt-inducible kinases (SIKs) are key metabolic regulators. Imbalance of SIK function is associated with the development of diverse cancers, including breast, gastric and ovarian cancer. Chemical tools to clarify the roles of SIK in different diseases are, however, sparse and are generally characterized by poor kinome-wide selectivity. Here, we have adapted the pyrido[2,3-d]pyrimidin-7-one-based PAK inhibitor G-5555 for the targeting of SIK, by exploiting differences in the back-pocket region of these kinases. Optimization was supported by high-resolution crystal structures of G-5555 bound to the known off-targets MST3 and MST4, leading to a chemical probe, MRIA9, with dual SIK/PAK activity and excellent selectivity over other kinases. Furthermore, we show that MRIA9 sensitizes ovarian cancer cells to treatment with the mitotic agent paclitaxel, confirming earlier data from genetic knockdown studies and suggesting a combination therapy with SIK inhibitors and paclitaxel for the treatment of paclitaxel-resistant ovarian cancer.
Snazarus and its human ortholog SNX25 regulate autophagic flux by affecting VAMP8 endocytosis
Authors: Lauzier Annie , Bossanyi Marie-France , Ugrankar Rupali , Mike Henne W. , Jean Steve
Published: April 2021

Autophagy, the degradation and recycling of cytosolic components in the lysosome, is an essential cellular mechanism. It is a membrane-mediated process that is linked to vesicular trafficking events. The sorting nexin (SNX) protein family controls the sorting of a large array of cargoes, and various SNXs can impact autophagy. To gain a better understanding of their functionsin vivounder nutrient starvation, we screened allDrosophilaSNXs by RNAi in the fat body. Significantly, depletion ofsnazarus(snz) strongly impacted autolysosome formation and led to decreased autophagic flux. Interestingly, we observed altered distribution of Vamp7-positive vesicles with snz depletion andsnzroles were conserved in human cells.SNX25is the closest ortholog tosnz, and we demonstrate a role for it in VAMP8 trafficking. We found that this activity was dependent on theSNX25PX domain, and independent ofSNX25anchoring at the ER. We also demonstrate that differentially spliced forms ofSNX14andSNX25are present in cancer cells. This work identifies a conserved role forsnz/SNX25as regulators of autophagic flux, and show differential isoform expression between orthologs.
Interpretation of allele-specific chromatin accessibility using cell state–aware deep learning
Authors: Atak Zeynep Kalender , Taskiran Ibrahim Ihsan , Demeulemeester Jonas , Flerin Christopher , Mauduit David , Minnoye Liesbeth , Hulselmans Gert , Christiaens Valerie , Ghanem Ghanem-Elias , Wouters Jasper , Aerts Stein
Published: April 2021

Genomic sequence variation within enhancers and promoters can have a significant impact on the cellular state and phenotype. However, sifting through the millions of candidate variants in a personal genome or a cancer genome, to identify those that impact cis-regulatory function, remains a major challenge. Interpretation of noncoding genome variation benefits from explainable artificial intelligence to predict and interpret the impact of a mutation on gene regulation. Here we generate phased whole genomes with matched chromatin accessibility, histone modifications, and gene expression for 10 melanoma cell lines. We find that training a specialized deep learning model, called DeepMEL2, on melanoma chromatin accessibility data can capture the various regulatory programs of the melanocytic and mesenchymal-like melanoma cell states. This model outperforms motif-based variant scoring, as well as more generic deep learning models. We detect hundreds to thousands of allele-specific chromatin accessibility variants (ASCAVs) in each melanoma genome, of which 15%–20% can be explained by gains or losses of transcription factor binding sites. A considerable fraction of ASCAVs are caused by changes in AP-1 binding, as confirmed by matched ChIP-seq data to identify allele-specific binding of JUN and FOSL1. Finally, by augmenting the DeepMEL2 model with ChIP-seq data for GABPA, the TERT promoter mutation, as well as additional ETS motif gains, can be identified with high confidence. In conclusion, we present a new integrative genomics approach and a deep learning model to identify and interpret functional enhancer mutations with allelic imbalance of chromatin accessibility and gene expression.
The α-D-anomer of 2′-deoxycytidine: crystal structure, nucleoside conformation and Hirshfeld surface analysis
Authors: Budow-Busse Simone , Chai Yingying , Müller Sebastian Lars , Daniliuc Constantin , Seela Frank
Published: April 2021

β-2′-Deoxyribonucleosides are the constituents of nucleic acids, whereas their anomeric α-analogues are rarely found in nature. Moreover, not much information is available on the structural and conformational parameters of α-2′-deoxyribonucleosides. This study reports on the single-crystal X-ray structure of α-2′-deoxycytidine, C9H13N3O4(1), and the conformational parameters characterizing1were determined. The conformation at the glycosylic bond isanti, with χ = 173.4 (2)°, and the sugar residue adopts an almost symmetrical C2′-endo-C3′-exotwist (23T;S-type), withP= 179.7°. Both values lie outside the conformational range usually preferred by α-nucleosides. In addition, the amino group at the nucleobase shows partial double-bond character. This is supported by two separated signals for the amino protons in the1H NMR spectrum, indicating a hindered rotation around the C4—N4 bond and a relatively short C—N bond in the solid state. Crystal packing is controlled by N—H...O and O—H...O contacts between the nucleobase and sugar moieties. Moreover, two weak C—H...N contacts (C1′—H1′ and C3′—H3′A) are observed. A Hirshfeld surface analysis was carried out and the results support the intermolecular interactions observed by the X-ray analysis.
Not a stranger to the dark: discrimination against autistic students and employees
Authors: Lorenz Timo , Brüning Chelsea Rebecca , Waltz Mitzi , Fabri Marc
Published: April 2021

Purpose

The purpose of this paper is to reveal barriers and their coherences between discrimination and self-perceived employability which students and employees on the autism spectrum often face and need to overcome. These include discrimination based on disability, when applying for a job or retaining employment. This research located barriers in three different categories: formality – problems that focus on organizational structures in the application process; social – communication and interaction problems; and job demand barriers – obstacles that epitomize work-related strains.

Design/methodology/approach

Barriers and discrimination can prevent individuals from accessing the labor market which can lead to severe consequences for an individual on the autism spectrum, such as poverty, social deprivation or lack of health promotion and equal treatment. Self-perceived employability can be regarded as an additional strength, as it describes the perception of an individual’s own skills and versatility to acquire and keep a job. In total, 53 German-speaking individuals on the autism spectrum participated in an online survey.

Findings

Results showed statistically significant coherences between both, formality and social barriers with discrimination. Formality barriers also indicated statistically significant coherences with self-perceived employability. A mediation model with discrimination as mediator between each category of barriers and self-perceived employability was examined. The non-significant results suggest that discrimination does not work as a superior construct but as a sole influence next to barriers and self-perceived employability.

Originality/value

Individuals on the autism spectrum epitomize a less common research approach. Moreover, diversity policies and practices in the workplace often do not focus on including individuals on the autism spectrum even though the employment rates for this specific group of potential highly qualified employees were reported to be consistently lower when compared to any other group of disabled people. Findings suggest possible starting points for future research, which are discussed alongside practical strategies to overcome barriers and change discriminatory attitudes toward skilled individuals on the autism spectrum.
How far are we from understanding corruption? The effect of cultural distance on corruption perception
Authors: Szymanski Mike , Valdovinos Ivan , Kaltenecker Evodio
Published: April 2021

Purpose

This study aims to examine the relationship between cultural distances between countries and their scores in the Corruption Perception Index (CPI), which is the most commonly used measure of corruption in international business (IB) research.

Design/methodology/approach

The authors applied fixed-effect (generalized least squares) statistical modeling technique to analyze 1,580 year-country observations.

Findings

The authors found that the CPI score is determined to a large extent by cultural distances between countries, specifically the distance to the USA and to Denmark.

Research limitations/implications

CPI is often used as a sole measure of state-level corruption in IB research. The results show that the measure is significantly influenced by cultural differences and hence it should be applied with great caution, preferably augmented with other measures.

Originality/value

To the best of the authors’ knowledge, this is the first study to look at cultural distances as determinants of CPI score. The authors empirically test whether the CPI is culturally biased.
Toll-based access vs pirate access: a webometric study of academic publishers
Authors: Amin Raashida , Ayoub Arshia , Amin Sumeera , Wani Zahid Ashraf
Published: April 2021

Purpose

The purpose of this paper is to draw a comparison of the Web traffic ranking, usage and popularity of websites of databases of reputed publishers, namely, ScienceDirect and Emerald Insight, that provide access on subscription basis with Sci-Hub, on the basis of data obtained from Alexa databank (www.alexa.com). Sci-Hub is a website that provides pirated open-access to the research literature, where piracy, according to The Economic Times (2020), refers to the unauthorized duplication of copyrighted content.

Design/methodology/approach

Under present study, the quantitative study of the collected data was carried out with help of descriptive research methodology. The Alexa databank was singled out as the source of data. This study crawled through Alexa databank on 01.12.2019 and collected relevant data regarding Sci-Hub, ScienceDirect and Emerald Insight using the search terms Sci-hub.tw, Sciencedirect.com and Emeraldinsight.com sequentially. Different criteria were taken into consideration, which include global traffic rank, the average number of page views per user, time taken for uploading, bounce rate, percentage of users, the number of in-links and daily time spent on the site.

Findings

The results of this study showed that ScienceDirect has the highest traffic rank and in-linking sites among the surveyed databases. But highest number of page visits were recorded for Sci-Hub with fastest downloading speed. It has also been observed that the users spent less time on ScienceDirect and Emerald Insight as compared to Sci-Hub. This study further observed that Sci-Hub has the lowest bounce rate. Users from both the developing and developed economies use the Sci-Hub, though the highest number of visitors belongs to the developing nations.

Originality/value

This study provides an overview of the performance of toll-based publishing databases with pirated database based on different criteria through World Wide Web. Though, this study in no way supports or endorses the unauthorized and illegal access to knowledge, but such data helps in depicting and analyzing how much a particular database is accessed by its users all over the globe and also determines and illustrates the time spent by users while accessing a specific database, thus, providing the user preferences in information seeking activities. This study provides an overall view of adoption of open resources.
The plight of racialised minorities during a pandemic: migrants and refugees in Italy and Australia
Authors: De Nardi Sarah , Phillips Melissa
Published: April 2021

Purpose

The purpose of this paper is to draw on data from interviews with six Italian migrant service providers and media stories in Italy and Australia to weave a comparative snapshot of the plight of precarious migrant and refugee communities in these two countries during the COVID-19 pandemic.

Design/methodology/approach

The article draws attention to prejudicial shortcomings towards vulnerable migrant communities enacted by the states of Italy and Australia in response to COVID-19.

Findings

While the unequal ecology of the pandemic has flared up the need for the State to strengthen participation and inclusion policies, it has also provided opportunities to foreground the disadvantages vulnerable communities face that also demand policy attention and sustained funding. Governments in migrant-receiving countries like Australia and Italy need to articulate culturally sensitive and inclusive responses that foreground agencies give vulnerable migrants, asylum seekers and refugees clear, supportive messages of solidarity leading to practical solutions.

Originality/value

This paper relays preliminary data from the coalface (migrant service providers) and media as the pandemic evolved in the two countries, whose support mechanisms had never before been critically compared and evaluated through the lens of racial inequality in the face of a health and social crisis.
Engaging Gen Z in professional selling: a systematic literature review
Authors: Loring Andrew , Wang Jia
Published: April 2021

Purpose

Employee engagement literature pertaining to professional salespeople has revealed several antecedents and consequences that lead to greater performance and turnover reduction. However, engagement literature in the field of human resource development (HRD) does not account for Generation Z (Gen Z), the latest in the workforce who has been noted to be vastly different from previous generations. This study aims to explore how to engage Gen Z in the context of professional selling by identifying the antecedents and consequences of employee engagement based on individual characteristics and organizational needs of this group.

Design/methodology/approach

A systematic literature review was conducted. In total, 21 papers relevant to employee engagement, professional selling and Gen Z were critically analyzed.

Findings

Findings indicate that Gen Z’s organizational need for mentoring and their individual characteristic of wanting job control and ownership are vital antecedents that could increase employee engagement. In addition, competitive rewards are important consequences that could improve individual sales performance.

Practical implications

HRD practitioners and organizational leaders must understand the unique characteristics of Gen Z to effectively engage them in the workplace. For sales organizations, there is a critical need to offer mentoring opportunities and competitive rewards from the start of Gen Z salespeople’s employment.

Originality/value

This research expands current engagement literature by addressing an emerging, under-explored issue – how to engage the newest workforce, Gen Z, in the context of professional selling.
Application of tools and techniques of quality by design in pharmaceutical process
Authors: Gijo E.V.
Published: April 2021

Purpose

The purpose of this article is to demonstrate the application of the tools and techniques of Quality by Design (QbD) approach in an Indian pharmaceutical drug product manufacturing company and to understand the challenges, managerial implications and lessons learned while implementing this initiative.

Design/methodology/approach

This work adopts the Action Research methodology for impurity reduction in a drug product manufacturing company in India by using the tools and techniques of QbD approach. Various QbD tools like Design of experiments, process capability evaluation and control charts were effectively utilized for the study.

Findings

As a part of QbD implementation in the organization, a specific drug product was identified and the impurity level in the product was studied. Significant variables impacting the impurity were identified and the optimum levels for the significant variables were identified through design of experiments. The solutions were implemented and the impurity levels were reduced significantly.

Research limitations/implications

Even though the article is based on a single case study related to tools and techniques of QbD in a single organization in India, the identified problem is a generic product quality related issue for any pharmaceutical drug product manufacturing company. Hence the findings of this research are applicable to pharmaceutical drug manufacturing industry in general.

Originality/value

This article illustrates the systematic usage of various tools and techniques of QbD methodology in a pharmaceutical drug product manufacturing company. The usage of Design of Experiments for process optimization and application of other tools and techniques are ready references for the practitioners and novice users in the field.
Enabling design: a case of maker workshops as a method for including special educators in creating digital interactions for learners with profound disabilities
Authors: Keay-Bright Wendy Elizabeth , Eslambolchilar Parisa , Taylor Aidan
Published: April 2021

Purpose

This purpose of this paper is to present findings from three workshops that aimed to enable learners with profound and multiple learning disabilities to have a richer, more meaningful experience of a digital curriculum and to bolster a more meaningful creative exchange than currently offered by off the shelf products.

Design/methodology/approach

Informed by the maker culture and participatory action research, this workshop method focussed on making prototypes and creating concepts that encourage a dialogic approach for envisioning future technologies. As a process of enabling design, this approach placed participants at the heart of iterative methods that support imaginative ideation and improvisation, rather than the production of marketable products.

Findings

A thematic analysis of post-workshop discussions revealed that participants felt inspired and supported to envision learner responses to stimuli as novel interactions, without prior knowledge of designing and coding. The collaborative approach provoked the articulation of narratives on learner ability and a reconsideration of “digital” with a contemporary curriculum for learners with profound disabilities.

Practical implications

Running a maker workshop requires a time and resource commitment from all parties. The emphasis is on easy-to-follow, direct teaching together with low cost electronics and non-digital materials, ensured that these demands were kept to a minimum. However, the gains of participation can only be maintained when support exists both in and out of the workshop environment through the provision of resources and communication channels.

Originality/value

The originality of the workshops lies in the focus on basic electronics, coding and prototyping as a means to think about digital futures. As a method of enabling technologies to tap into learner ability, this process fostered design dialogues through the social act of making, sharing and learning without the need for prerequisite skills.
Research output of Indian universities in sciences (2015–2019): a scientometric analysis
Authors: Mahala Avijit , Singh Rajesh
Published: April 2021

Purpose

The present study aims to trace out the science research output of top Indian universities from 2015 to 2019, as reflected in the Web of Science (WOS) database.

Design/methodology/approach

The present study has selected the Science Citation Index (SCI) of WOS core collection for selecting top Indian universities in terms of total publications in the last five years (2015–2019). The University of Delhi (DU), Banaras Hindu University (BHU), Anna University (AU), Jadavpur University (JU) and Punjab University (PU) have been selected. The study identified the most prolific authors, collaborating countries, collaborating institutions and the impact of their output in terms of citations per paper (CPP) and relative citation impact (RCI). For visualizing purposes, VOSviewer was used. The study also identified frequently used keywords and channels used for communicating research results.

Findings

The authors retrieved 26,173 documents consisting of journal articles, review papers and proceeding papers. The consistent growth of science research output has been observed. The University of Delhi (DU) has the maximum science publications. The study reflects that multi-authored papers have more research impact in terms of citation received. The USA, South Korea and Germany are the most collaborating countries. The top Indian Universities have a major collaboration with Anna University, Indian Institute of Technology, Center for Scientific and Industrial Research (CSIR) of India.

Originality/value

The present study reveals how the science research output of top Indian universities has grown in the last few years. The findings of the study can be used for identifying specific science research areas where special attention can be given.
Stakeholder relationships in off-site construction: a systematic literature review
Authors: Nguyen Bao Ngoc , London Kerry , Zhang Peng
Published: April 2021

Purpose

This paper aims to report a comprehensive analysis of literature on stakeholder relationships towards identifying patterns of relationships within the off-site construction context.

Design/methodology/approach

Key scholarly databases were accessed and after a filtering process, 74 relevant papers were retrieved for analysis. The papers were analysed using qualitative content analysis and scientometric techniques through the application of software Leximancer and VOSviewer.

Findings

Research synthesis methods used in the present study generate compatible results. Through text mining analysis, the key themes identified in the off-site construction stakeholder relationships literature included “collaboration”, “building information modelling”, “social network analysis”, supply chain. As a finding by scientometric analysis, collaboration, BIM, supply chain management, housing and social network analysis were the most frequently entered keywords context of off-site construction. Regarding authorship pattern, the whole network of collaboration was fragmented into multiple isolated clusters, implying that the authors had tendency to cooperate in small groups.

Practical implications

The paper can bring together an important area of research not previously studied in detail. It will primarily assist academics in the first instance; however, the research leads to important findings that will ultimately assist policymakers and practitioners better understand factors affecting stakeholder relationships and in particular network thinking and collaborative mind-sets.

Originality/value

The review contributes a needed systematic and theoretical foundation for future stakeholder relationship studies and practices in off-site construction sector. It provides the basis for future studies and is a seminal analysis of stakeholder management and off-site construction. The scientometric methodology offers scholars a different approach to analysing and visualising literature reviews.
A dynamic model of crisis management from a stakeholder perspective: the case of COVID-19 in China
Authors: Li Bin , Zhang Tingting , Hua Nan , Wang Youcheng
Published: April 2021

Purpose

This study aims to develop a holistic and dynamic model that governs the various relationships among the critical factors of crisis management from a stakeholder perspective in the context of China’s COVID-19 epidemic outbreak.

Design/methodology/approach

Data were collected from 731 textual sources, and the text mining technique identified the themes of a holistic crisis management model. Then, content analysis was applied to reveal in-depth insights into the themes.

Findings

From a stakeholder perspective, the model comprises six elements: political environment, economic environment, technology, social environment, health and science and international relationships, which relate significantly to four procedural actions: prevention, response, recovery and adaptation. The overlapping stages and situational dynamic mechanisms of the process are another two new major findings of this study; learning and preparing are threaded throughout the whole dynamic process.

Practical implications

Hospitality stakeholders are advised to collaborate under the guidance of the dynamic crisis management model and adopt high-technology tools for the industry’s recovery management. Developing a new business model and marketing strategy is a useful approach to face similar crisis management challenges in the future.

Originality/value

This paper fills an existing research gap by presenting a health-related crisis management model that can be used to evaluate the dynamic process of collaborations among stakeholders in coping with external challenges forced upon the hospitality industry.