bluuebunny/crossref_metadata_2025 huggingface dataset:
Induce Pluripotency via Specific distal enhancer-promoter associations
Authors: Zhu Xiusheng , Huang Lei , Li Dongwei , Luo Jing , Huang Qitong , Wang Xueyan , Zhang Yubo
Published: June 2021

Induced pluripotent stem cell (iPSC) technology promises to be an inexhaustible source of any type of cell needed for therapeutic and research purposes. It is unclear that how distal enhancer-promoter associations/ 3D chromatin conformation involving in the capacity of self-renewal and pluripotency maintenance. In this study, we have selected a few defined enhancer-promoter associations. After screening of enhancer specificity and activity individually, we design the different combinations and transfect these enhancers into the MEF cells. We simultaneously transfect 7 determined enhancers which represents various specific distal chromatin associations into a GFP tracing MEF cell line. We observe that the MEF cells start generating iPS-like clones at day 22. Importantly, our validations with three germ layer marker genes and in vitro experiments have further confirmed the pluripotency of these clones. Here, our study proposes a potential de novo method of a low-genetic risk iPS generation by introducing spatiotemporal distal chromatin associations. This result also paves out the way on utilizing 3D genomic information to alter cell identity and reprogramming for potential therapeutic strategy.
Monod model is insufficient to explain biomass growth in nitrogen-limited yeast fermentation
Authors: Henriques David , Balsa-Canto Eva
Published: June 2021

The yeastSaccharomyces cerevisiaeis an essential microorganism in food biotechnology; particularly, in wine and beer making. During wine fermentation, yeasts transform sugars present in the grape juice into ethanol and carbon dioxide. The process occurs in batch conditions and is, for the most part, an anaerobic process. Previous studies linked limited-nitrogen conditions with problematic fermentations, with negative consequences for the performance of the process and the quality of the final product. It is, therefore, of the highest interest to anticipate such problems through mathematical models. Here we propose a model to explain fermentations under nitrogen-limited anaerobic conditions. We separated the biomass formation into two phases: growth and carbohydrate accumulation. Growth was modelled using the well-known Monod equation while carbohydrate accumulation was modelled by an empirical function, analogous to a proportional controller activated by the limitation of available nitrogen. We also proposed to formulate the fermentation rate as a function of the total protein content when relevant data are available. The final model was used to successfully explain experiments taken from the literature, performed under normal and nitrogen-limited conditions. Our results revealed that Monod model is insufficient to explain biomass formation kinetics in nitrogen-limited fermentations ofS. cerevisiae. The goodness-of-fit of the herewith proposed model is superior to that of previously published models, offering the means to predict, and thus control fermentations.

Importance

Problematic fermentations still occur in the winemaking industrial practise. Problems include sluggish rates of fermentation, which have been linked to insufficient levels of assimilable nitrogen. Data and relevant models can help anticipate poor fermentation performance. In this work, we proposed a model to predict biomass growth and fermentation rate under nitrogen-limited conditions and tested its performance with previously published experimental data. Our results show that the well-known Monod equation does not suffice to explain biomass formation.
Fuzzy RNA-recognition by theTrypanosoma bruceieditosome
Authors: Leeder Wolf-Matthias , Göringer H. Ulrich
Published: June 2021

The recognition of RNA-molecules by proteins and protein complexes is a critical step on all levels of gene expression. Typically, the generated ribonucleoprotein complexes rely on the binary interaction of defined RNA-sequences or precisely folded RNA-motifs with dedicated RNA-binding domains on the protein side. Here we describe a new molecular recognition principle of RNA-molecules by a high molecular mass protein complex. By chemically probing the solvent accessibility of mitochondrial pre-mRNAs when bound to theTrypanosoma bruceieditosome we identified multiple similar but nonidentical RNA-motifs as editosome contact sites. However, by treating the different motifs as mathematical graph objects we demonstrate that they fit a consensus 2D-graph consisting of 4 vertices (V) and 3 edges (E) with a Laplacian eigenvalue of 0.523 (λ2). We establish that a synthetic 4V(3E)-RNA is sufficient to compete for the editosomal pre-mRNA binding site and that it is able to inhibit RNA-editingin vitro. Our analysis corroborates that the editosome has adapted to the structural multiplicity of the mitochondrial mRNA-folding space by recognizing a fuzzy continuum of RNA-folds that fit a consensus graph-descriptor. This provides a mechanism on how the protein complex is able to bind the structurally pleomorphic pool of pre- and partially edited mRNAs. We speculate that other fuzzy RNA-recognition motifs exist especially for proteins that interact with multiple RNA-species.
Psychophysical evidence and perceptual observations show that object recognition is not hierarchical but is a parallel, simultaneous, egalitarian, non-computational system
Authors: Gur Moshe
Published: June 2021

Object recognition models have at their core similar essential characteristics: feature extraction and hierarchical convergence leading to a code that is unique to each object and immune to variations in the object appearance. To compare computational, biologically-feasible models to human performance, subjects viewed objects displayed at a wide range of orientations and sizes, and were able to recognize them almost perfectly. These empirical results, together with consideration of thought experiments and analysis of everyday perceptual performance, lead to a conclusion that biologically-plausible object perception models do not even come close to matching our perceptual abilities. We can categorize many thousands of objects, discriminate between enormous numbers of different exemplars within each category, and recognize an object as unique although it may appear in countless variations―most of which have never been seen. This seemingly technical, quantitative failure stems from a fundamental property of our perception: the ability to perceive spatial information instantaneously and in parallel, retain details including their relative properties, and yet be able to integrate details into a meaningful percept such as an object. I present an alternative view of object perception whereby objects are represented by responses in primary visual cortex (V1) which is the only cortical area responding to small spatial elements. The rest of the visual cortex is dedicated to scene understanding and interpretation such as constructing 3D percepts from 2D inputs, coding motion, categorization and memories. Since our perception abilities cannot be explained by convergence to “object cells” or by interactions implemented by axonal transmissions, a parallel-to-parallel field-like process is suggested. In this view, spatial information is not modified by multiple neural interactions but is retained by affecting changes in a “neural field” which preserves the identity of individual elements while enabling a new holistic percept when these elements change.
Computational inference, validation, and analysis of 5’UTR-leader sequences of alleles of immunoglobulin heavy chain variable genes
Authors: Huang Yixun , Thörnqvist Linnea , Ohlin Mats
Published: June 2021

Upstream and downstream sequences of immunoglobulin genes may affect the expression of such genes. However, these sequences are rarely studied or characterized in most studies of immunoglobulin repertoires. Inference from large, rearranged immunoglobulin transcriptome data sets offers an opportunity to define the upstream regions (5’-untranslated regions and leader sequences). We have now established a new data pre-processing procedure to eliminate artifacts caused by a 5’-RACE library generation process, reanalyzed a previously studied data set defining human immunoglobulin heavy chain genes, and identified novel upstream regions, as well as previously identified upstream regions that may have been identified in error. Upstream sequences were also identified for a set of previously uncharacterized germline gene alleles. Several novel upstream region variants were validated, for instance by their segregation to a single haplotype in heterozygotic subjects. SNPs representing several sequence variants were identified from population data. Finally, based on the outcomes of the analysis, we define a set of testable hypotheses with respect to the placement of particular alleles in complex IGHV locus haplotypes, and discuss the evolutionary relatedness of particular heavy chain variable genes based on sequences of their upstream regions.
Enteric glial cells favour accumulation of anti-inflammatory macrophages during the resolution of muscularis inflammation
Authors: Stakenborg Michelle , Abdurahiman Saeed , De Simone Veronica , Goverse Gera , Stakenborg Nathalie , van Baarle Lies , Wu Qin , Pirottin Dimitri , Kim Jung-Seok , Chappell-Maor Louise , Pintelon Isabel , Thys Sofie , Boon Louis , Hao Marlene , Van Ginderachter Jo A. , Boeckxstaens Guy E. , Timmermans Jean-Pierre , Jung Steffen , Marichal Thomas , Ibiza Sales , Matteoli Gianluca
Published: June 2021

Objective

Monocyte-derived macrophages (Mφs) are crucial regulators during muscularis inflammation. However, it is unclear which microenvironmental factors are responsible for monocyte recruitment and neurotrophic Mφ differentiation in this paradigm. Here, we investigate Mφ heterogeneity at different stages of muscularis inflammation and determine how environmental cues can attract and activate tissue protective Mφs.

Design

Single cell RNA sequencing was performed on immune cells from the muscularis of wild-type and CCR2-/- mice at different timepoints after muscularis inflammation. CX3CR1GFP/+ and CX3CR1CreERT2 R26YFP mice were analyzed by flow cytometry and immunofluorescence. The transcriptome of enteric glial cells (EGCs) was investigated using PLPCreERT2 Rpl22HA mice. In addition, we assessed the effect of supernatant from neurosphere-derived EGCs on monocyte differentiation based on the expression of pro- and anti-inflammatory factors.

Results

Muscularis inflammation induced marked alterations in mononuclear phagocyte populations associated with a rapid infiltration of Ly6c+ monocytes that locally acquired unique transcriptional states. Trajectory inference analysis revealed two main pro-resolving Mφ subpopulations during the resolution of muscularis inflammation, i.e. Cd206+ MhcIIhi and Timp2+ MhcIIlo Mφs, which were both derived from CCR2+ monocytes. Interestingly, we found that EGCs were able to sense damage to the muscularis to stimulate monocyte recruitment and differentiation towards pro-resolving Mφs via CCL2 and CSF1, respectively.

Conclusion

Our study provides a comprehensive insight into pro-resolving Mφ differentiation and their regulators during muscularis inflammation. We deepened our understanding in the interaction between EGCs and Mφs, thereby highlighting pro-resolving Mφ differentiation as a potential novel therapeutic strategy for the treatment of intestinal inflammation.
Ghrelin proteolysis by insulin-degrading enzyme
Authors: Bocach David D. , Jones Kierstin L. , Bell Jonathan M. , Zheng Qiuchen , Lazo Noel D. , Smith-Carpenter Jillian E. , Alper Benjamin J.
Published: June 2021

Here we report proteolysis of synthetic acylated human ghrelin by recombinant human insulin-degrading enzyme (IDE). Kinetic parameters and sites of proteolytic cleavage were evaluated. Ghrelin proteolysis by IDE was inhibited by ethylenediaminetetraacetate (EDTA), a metal chelating agent. Ghrelin proteolysis appears at least somewhat specific to M16 family proteases such as IDE, as the M13 protease neprilysin (NEP) did not exhibit ghrelin proteolysis in this study. A quenched fluorogenic peptide substrate comprising the primary sites of IDE-mediated ghrelin proteolysis (Mca-QRVQQRKESKK(Dnp)-OH; Mca: 7-methoxycoumarin-3-carboxylic acid; Dnp: 2,4-dinitrophenyl) was developed and used to evaluate enzyme specificity and kinetic parameters of proteolysis. Like acyl ghrelin, Mca-QRVQQRKESKK(Dnp)-OH was efficiently cleaved by IDE central to the target sequence. We anticipate that this quenched fluorogenic peptide substrate will be of value to future studies of ghrelin proteolysis by IDE and potentially other peptidases.
CANT-HYD: A curated database of phylogeny-derived Hidden Markov Models for annotation of marker genes involved in hydrocarbon degradation
Authors: Khot Varada , Zorz Jackie , Gittins Daniel A. , Chakraborty Anirban , Bell Emma , Bautista María A. , Paquette Alexandre J. , Hawley Alyse K. , Novotnik Breda , Hubert Casey R. J. , Strous Marc , Bhatnagar Srijak
Published: June 2021

Discovery of microbial hydrocarbon degradation pathways has traditionally relied on laboratory isolation and characterization of microorganisms. Although many metabolic pathways for hydrocarbon degradation have been discovered, the absence of tools dedicated to their annotation makes it difficult to identify the relevant genes and predict the hydrocarbon degradation potential of microbial genomes and metagenomes. Furthermore, sequence homology between hydrocarbon degradation genes and genes with other functions often results in misannotation. A tool that systematically identifies hydrocarbon metabolic potential is therefore needed. We present the Calgary approach to ANnoTating HYDrocarbon degradation genes (CANT-HYD), a database containing HMMs of 37 marker genes involved in anaerobic and aerobic degradation pathways of aliphatic and aromatic hydrocarbons. Using this database, we show that hydrocarbon metabolic potential is widespread in the tree of life and identify understudied or overlooked hydrocarbon degradation potential in many phyla. We also demonstrate scalability by analyzing large metagenomic datasets for the prediction of hydrocarbon utilization in diverse environments. To the best of our knowledge, CANT-HYD is the first comprehensive tool for robust and accurate identification of marker genes associated with aerobic and anaerobic hydrocarbon degradation.
Calcium-permeable cation channels are involved in uranium uptake in Arabidopsis thaliana
Authors: Sarthou Manon C.M. , Devime Fabienne , Baggio Célia , Figuet Sylvie , Alban Claude , Bourguignon Jacques , Ravanel Stéphane
Published: June 2021

Uranium (U) is a non-essential and toxic element that is taken up by plants from the environment. The assimilation pathway of U is still unknown in plants and any other organism. In this study, we provide several evidences that U is taken up by the roots of Arabidopsis thaliana through Ca2+-permeable cation channels. First, we showed that deprivation of Arabidopsis plants with calcium induced a 1.5-fold increase in the capacity of roots to accumulate U, suggesting that calcium deficiency promoted the radionuclide import pathway. Second, we showed that external calcium inhibits U accumulation in roots, suggesting a common route for the uptake of both cations. Third, we found that gadolinium, nifedipine and verapamil inhibit the absorption of U, suggesting that different types of Ca2+-permeable channels serve as a route for U uptake. Last, we showed that U bioaccumulation in Arabidopsis mutants deficient for the Ca2+-permeable channels MCA1 and ANN1 was decreased by 40%. This suggests that MCA1 and ANN1 contribute to the absorption of U in different zones and cell layers of the root. Together, our results describe for the first time the involvement of Ca2+-permeable cation channels in the cellular uptake of U.
High-affinity iron and calcium transport pathways are involved in U(VI) uptake in the budding yeast Saccharomyces cerevisiae
Authors: Revel Benoît , Catty Patrice , Ravanel Stéphane , Bourguignon Jacques , Alban Claude
Published: June 2021

Uranium (U) is a naturally-occurring radionuclide toxic for living organisms that can take it up. To date, the mechanisms of U uptake are far from being understood. Here, we used the yeast Saccharomyces cerevisiae as a unicellular eukaryote model to identify U assimilation pathways. Thus, we have identified, for the first time, transport machineries capable of transporting U in a living organism. First, we evidenced a metabolism-dependent U transport in yeast. Then, competition experiments with essential metals allowed us to identify calcium, iron and copper entry pathways as potential routes for U uptake. The analysis of various metal transport mutants revealed that mid1Δ, cch1Δ and ftr1Δ mutants, affected in calcium (Mid1/Cch1 channel) and Fe(III) (Ftr1/Fet3 complex) transport, respectively, exhibited highly reduced U uptake rates and accumulation, demonstrating the implication of these import systems in U uptake. Finally, expression of the Mid1 gene into the mid1Δ mutant restored U uptake levels of the wild type strain, underscoring the central role of the Mid1/Cch1 calcium channel in U absorption process in yeast. Our results also open up the opportunity for rapid screening of U-transporter candidates by functional expression in yeast, before their validation in more complex higher eukaryote model systems.

Highlights

Living yeast Saccharomyces cerevisiae is able to take up U

Availability of a metabolizable substrate stimulates U uptake

Calcium, iron and copper inhibit U uptake

Strains deleted in Mid1/Cch1 calcium channel and Ftr1 iron permease are affected in U uptake

Expression of MID1 gene in mid1Δ strain restore wild type levels of U uptake

Graphical Abstract
The Consciousness Theories Studies (ConTraSt) database: analyzing and comparing empirical studies of consciousness theories
Authors: Yaron Itay , Melloni Lucia , Pitts Michael , Mudrik Liad
Published: June 2021

Understanding how consciousness arises from neural activity remains one of the biggest challenges for neuroscience. Numerous theories have been proposed in recent years, each gaining independent empirical support. Currently, there is no comprehensive, quantitative and theory-neutral overview of the field that enables an evaluation of how theoretical frameworks interact with empirical research. We provide a bird’s eye view on studies that interpreted their findings in light of at least one of four leading neuroscientific theories of consciousness (N=412 experiments), asking how methodological choices of the researchers might affect the final conclusions. We found that supporting a specific theory can be predicted solely from methodological choices, irrespective of findings. Furthermore, most studies interpret their findings post-hoc, rather than a-priori testing critical predictions of the theories. Our results highlight challenges for the field and provide researchers with a unique, open-access website to further analyze trends in the neuroscience of consciousness.
The dynamic properties of a nuclear coactivator binding domain are evolutionarily conserved
Authors: Karlsson Elin , Sorgenfrei Frieda A. , Andersson Eva , Dogan Jakob , Jemth Per , Chi Celestine N.
Published: June 2021

Evolution of proteins is constrained by their structure and function. While there is a consensus that the plasticity of intrinsically disordered proteins relaxes the structural constraints on evolution there is a paucity of data on the molecular details of these processes. The Nuclear co-activator binding domain (NCBD) from CREB-binding protein is a protein-protein interaction domain, which contains a hydrophobic core but is not behaving as a typical globular domain, and has been desribed as ‘molten-globule like’. The highly dynamic properties of NCBD makes it an interesting model system for evolutionary structure-function investigation of intrinsically disordered proteins. We have here compared the structure and biophysical properties of an ancient version of NCBD present in a bilaterian animal ancestor living around 600 million years ago with extant human NCBD. Using a combination of NMR spectroscopy, circular dichroism and kinetic methods we show that although NCBD has increased its thermodynamic stability, it has retained its dynamic biophysical properties in the ligand-free state in the evolutionary lineage leading from the last common bilaterian ancestor to humans. Our findings suggest that the dynamic properties of NCBD have been maintained by purifying selection and thus are important for its function, which includes mediating several distinct protein-protein interactions.
Shape-restrained modelling of protein-small molecule complexes with HADDOCK
Authors: Koukos Panagiotis I. , Réau Manon , Bonvin Alexandre M. J. J.
Published: June 2021

Small molecule docking remains one of the most valuable computational techniques for the structure prediction of protein-small molecule complexes. It allows us to study the interactions between compounds and the protein receptors they target at atomic detail, in a timely and efficient manner. Here we present a new protocol in HADDOCK, our integrative modelling platform, which incorporates homology information for both receptor and compounds. It makes use of HADDOCK’s unique ability to integrate information in the simulation to drive it toward conformations which agree with the provided data. The focal point is the use of shape restraints derived from homologous compounds bound to the target receptors. We have developed two protocols: In the first, the shape is composed of fake atom beads based on the position of the heavy atoms of the homologous template compound, whereas in the second the shape is additionally annotated with pharmacophore data, for some or all beads. For both protocols, ambiguous distance restraints are subsequently defined between those beads and the heavy atoms of the ligand to be docked. We have benchmarked the performance of these protocols with a fully unbound version of the widely used DUD-E dataset. In this unbound docking scenario, our template/shape-based docking protocol reaches an overall success rate of 81% on 99 complexes, which is close to the best results reported for bound docking on the DUD-E dataset.

Table of contents graphic
Enhanced Immunoprecipitation Techniques for the Identification of RNA Binding Protein Partners: CRD-BP interactions in mammary epithelial cells
Authors: Fakhraldeen Saja A. , Berry Scott M. , Beebe David J. , Roopra Avtar , Spiegelman Vladimir S. , Alexander Caroline M.
Published: June 2021

RNA binding proteins (RBPs) regulate expression of large cohorts of RNA species to affect programmatic changes in cellular phenotypes. In order to describe the function of RBPs within a cell, it is key to identify their mRNA binding partners. This is often done by cross-linking nucleic acids to RBPs, followed by chemical release of the nucleic acid fragments for analysis. However, this methodology is lengthy, involves complex processing leading to extraordinary losses, requires large amounts of starting materials, and is prone to artifacts due to the labile nature of mRNA. To evaluate potential alternative technologies, we tested “exclusion-based” purification of immunoprecipitates (oil-based IFAST™ or air-based SLIDE™), and report here that these methods can efficiently, rapidly and specifically isolate RBP-RNA complexes with minimal handling. The analysis starts with >100x less material than for techniques that include cross-linking. Depending on the specific antibody used, 50-100% of starting protein is retrieved, allowing the assay of endogenous levels of RBP instead of tagged and over-expressed ectopic proteins. Isolated protein and nucleic acid components are purified and analyzed using standard techniques to provide a comprehensive portrait of RBP complexes. Using exclusion-based techniques, we show that the mRNA binding partners for CRD-BP/IMP1/IGF2BP1/ZBP1 in cultured mammary epithelial cells are enriched in mRNAs important for de-toxifying superoxides (glutathione metabolic enzymes) and other mRNAs encoding mitochondrial proteins.
A community-driven roadmap to advance research on translated open reading frames detected by Ribo-seq
Authors: Mudge Jonathan M. , Ruiz-Orera Jorge , Prensner John R. , Brunet Marie A. , Gonzalez Jose Manuel , Magrane Michele , Martinez Thomas , Schulz Jana Felicitas , Yang Yucheng T. , Albà M. Mar , Baranov Pavel V. , Bazzini Ariel , Bruford Elspeth , Martin Maria Jesus , Carvunis Anne-Ruxandra , Chen Jin , Couso Juan Pablo , Flicek Paul , Frankish Adam , Gerstein Mark , Hubner Norbert , Ingolia Nicholas T. , Menschaert Gerben , Ohler Uwe , Roucou Xavier , Saghatelian Alan , Weissman Jonathan , van Heesch Sebastiaan
Published: June 2021

Ribosome profiling (Ribo-seq) has catalyzed a paradigm shift in our understanding of the translational ‘vocabulary’ of the human genome, discovering thousands of translated open reading frames (ORFs) within long non-coding RNAs and presumed untranslated regions of protein-coding genes. However, reference gene annotation projects have been circumspect in their incorporation of these ORFs due to uncertainties about their experimental reproducibility and physiological roles. Yet, it is indisputable that certain Ribo-seq ORFs make stable proteins, others mediate gene regulation, and many have medical implications. Ultimately, the absence of standardized ORF annotation has created a circular problem: while Ribo-seq ORFs remain unannotated by reference biological databases, this lack of characterisation will thwart research efforts examining their roles. Here, we outline the initial stages of a community-led effort supported by GENCODE / Ensembl, HGNC and UniProt to produce a consolidated catalog of human Ribo-seq ORFs.
Meditation-induced effects on whole-brain structural and effective connectivity
Authors: De Filippi Eleonora , Escrichs Anira , Càmara Estela , Garrido César , Sánchez-Fibla Marti , Gilson Matthieu , Deco Gustavo
Published: June 2021

In the past decades, there has been a growing scientific interest in characterizing neural correlates of meditation training. Nonetheless, the mechanisms underlying meditation remain elusive. In the present work, we investigated meditation-related changes in structural and functional connectivities (SC and FC, respectively). For this purpose, we scanned experienced meditators and control (naive) subjects using magnetic resonance imaging (MRI) to acquire structural and functional data during two conditions, resting-state and meditation (focused attention on breathing). In this way, we aimed to characterize and distinguish both short-term and long-term modifications in the brain’s structure and function. First, we performed a network-based analysis of anatomical connectivity. Then, to analyze the fMRI data, we calculated whole-brain effective connectivity (EC) estimates, relying on a dynamical network model to replicate BOLD signals’ spatio-temporal structure, akin to FC with lagged correlations. We compared the estimated EC, FC, and SC links as features to train classifiers to predict behavioral conditions and group identity. The whole-brain SC analysis revealed strengthened anatomical connectivity across large-scale networks for meditators compared to controls. We found that differences in SC were reflected in the functional domain as well. We demonstrated through a machine-learning approach that EC features were more informative than FC and SC solely. Using EC features we reached high performance for the condition-based classification within each group and moderately high accuracies when comparing the two groups in each condition. Moreover, we showed that the most informative EC links that discriminated between meditators and controls involved the same large-scale networks previously found to have increased anatomical connectivity. Overall, the results of our whole-brain model-based approach revealed a mechanism underlying meditation by providing causal relationships at the structure-function level.
Discovering single-cell eQTLs from scRNA-seq data only
Authors: Ma Tianxing , Li Haochen , Zhang Xuegong
Published: June 2021

eQTL studies are essential for understanding genomic regulation. Effects of genetic variations on gene regulation are cell-type-specific and cellular-context-related, so studying eQTLs at a single-cell level is crucial. The ideal solution is to use both mutation and expression data from the same cells. However, current technology of such paired data in single cells is still immature. We present a new method, eQTLsingle, to discover eQTLs only with single cell RNA-seq (scRNA-seq) data, without genomic data. It detects mutations from scRNA-seq data and models gene expression of different genotypes with the zero-inflated negative binomial (ZINB) model to find associations between genotypes and phenotypes at single-cell level. On a glioblastoma and gliomasphere scRNA-seq dataset, eQTLsingle discovered hundreds of cell-type-specific tumor-related eQTLs, most of which cannot be found in bulk eQTL studies. Detailed analyses on examples of the discovered eQTLs revealed important underlying regulatory mechanisms. eQTLsingle is a unique powerful tool for utilizing the huge scRNA-seq resources for single-cell eQTL studies, and it is available for free academic use at https://github.com/horsedayday/eQTLsingle.
Improvement of precision in refinements of structure factors using convergent-beam electron diffraction patterns taken at Bragg-excited conditions
Authors: Aryal B. , Morikawa D. , Tsuda K. , Terauchi M.
Published: June 2021

A local structure analysis method based on convergent-beam electron diffraction (CBED) has been used for refining isotropic atomic displacement parameters and five low-order structure factors with sin θ/λ ≤ 0.28 Å−1 of potassium tantalate (KTaO3). Comparison between structure factors determined from CBED patterns taken at the zone-axis (ZA) and Bragg-excited conditions is made in order to discuss their precision and sensitivities. Bragg-excited CBED patterns showed higher precision in the refinement of structure factors than ZA patterns. Consistency between higher precision and sensitivity of the Bragg-excited CBED patterns has been found only for structure factors of the outer zeroth-order Laue-zone reflections with larger reciprocal-lattice vectors. Correlation coefficients among the refined structure factors in the refinement of Bragg-excited patterns are smaller than those of the ZA ones. Such smaller correlation coefficients lead to higher precision in the refinement of structure factors.
Theoretical and methodological milestones in international accounting research: the contributions of Jill L. McKinnon
Authors: Patel Chris , Harrison Graeme
Published: June 2021

Purpose

This paper chronicles Jill McKinnon's theoretical and methodological contributions to international accounting research generally and socio-cultural research specifically over a 25-year period, 1981–2006. The purposes are: (1) to apprise contemporary and future researchers in international accounting, working with a socio-cultural lens, of a major contributor and contribution to the historical origin and development of that lens; and (2) to revisit and reappraise McKinnon's identification of critical theoretical and methodological cautions to guide future research in international accounting.

Design/methodology/approach

The paper provides a historical narrative and contemporary appraisal of: (1) McKinnon's seminal doctoral research into the Japanese system of corporate reporting regulation using a holistic and dynamic socio-cultural model of social systems change; and (2) her contribution to the advancement of cross-cultural international accounting research including her critique of that research leading to the identification of cautions, the recognition and observance of which are critical to the development of contemporary and future research. The narrative is informed by historical context of time and space, and imbued and interwoven with the personal story of McKinnon both as human and humane.

Findings

McKinnon's research invoking holistic theoretical and methodological perspectives provides a continuing template and pathway to guide contemporary and future international accounting researchers and to shape the development of international accounting research. Her career, research and humanity leave a legacy distilled into four themes that serve as counsels for accounting research and researchers; eclecticism of world-view and method choice, rigour, holism and the importance of collegiality with and to the accounting research community.

Originality/value

The paper provides original insights into the personality, career development and research of an important contributor to international accounting research specifically and interdisciplinary research in accounting generally. The paper demonstrates empirically the importance of historical analysis, contextualized by time, space and person, in understanding and informing the present state of international accounting research and, hence, linking past, present and future.
Pathways toward entrepreneurial intention among Malaysian universities’ students
Authors: Bazkiaei Hanieh Alipour , Khan Noor Ullah , Irshad Ateeq-ur-Rehman , Ahmed Adeel
Published: June 2021

Purpose

Entrepreneurship is a vital source of job creation and a key driver in promoting economic growth. The Malaysian government encourages higher educational institutions (HEIs) to develop more competitive and innovative graduates for the economy so that Malaysia achieves high-income nation status by 2025. This study aims to investigate the mediating role of attitude toward entrepreneurship (ATE) in the relationship between key psychological factors, that is, subjective norm (SN), perceived behavior control (PBC), big-five (BF) personality traits, entrepreneurial motivation (EM) and educational factors (EFs) with entrepreneurial intention (EI) among Malaysian university students.

Design/methodology/approach

This study used a quantitative design based on a positivist approach. The adopted questionnaire was used as the survey instrument. The primary data were collected from a sample of 251 final-year students in the management field who were enrolled in research-intensive Malaysian universities. Data were analyzed through the structural equation modeling (SEM) technique using AMOS 24 software.

Findings

Findings confirmed that the BF personality traits, EM, PBC, SN, ATE and EFs were positively related to EI. Furthermore, ATE mediated the relationship between BF personality traits, EM, PBC, SN, EF, and EI among Malaysian university students.

Research limitations/implications

This research provides critical insights into the key antecedents, for example, psychological and EFs, in explaining the EI of university students and future graduates. However, results can only be generalized to research-intensive Malaysian universities.

Originality/value

This study investigated the relationship between psychological factors, that is, BF personality traits, EM, PBC, SN and EFs in predicting EI of Malaysian university students. ATE mediated the relationship between BF personality traits, EM, PBC, SN, EF and EI among these students.
Antecedents of organizational citizenship behavior towards the environment in manufacturing organizations: using a structural equation modeling approach
Authors: Khan Noor Ullah , Irshad Ateeq-ur-Rehman , Ahmad Saufi Roselina , Ahmed Adeel
Published: June 2021

Purpose

Organizations worldwide are integrating sustainability into their operations to reduce the damage they do to the environment and to earn a better reputation in society. Scholars have acknowledged the role of environmental transformational leadership (ETL) in creating pro-environmental behaviors (PEBs). The manufacturing sector has shown interest in accepting an environmental management system (EMS) and fostering a mechanism for what is called perceived support organizational support for the environment (POSE). Voluntary PEBs taking the form of organizational citizenship behavior toward the environment (OCBE) increasingly interests researchers because it is important for the success of the EMS in the manufacturing sector. This study aims to investigate the mediating role of the EMS and POSE in the relationship between ETL and OCBE within ISO14001-certified Malaysian manufacturing firms.

Design/methodology/approach

A quantitative design was used based on a positivist approach. The data of 216 manufacturing firms were targeted using random probability sampling via a survey questionnaire. Later, the data were analyzed through the structural equation modeling (SEM) method using the SmartPLS 3.3.3 software.

Findings

Research findings confirmed a significant direct positive relationship between ETL and OCBE. Also, they confirmed the mediating role of the EMS and POSE in the relationship between ETL and OCBE among ISO14001-certified Malaysian manufacturing firms.

Research limitations/implications

This research has vital ramifications for both managers and organizations. Manufacturing firms should modify the traditional OCB towards pro-environmental OCBE using key antecedents, e.g. ETL, EMS and POSE.

Originality/value

The study analyzed the impact of ETL on OCBE through the mediating role of PSOE and the EMS. Here the focus is on the impact of OCBE key antecedents, i.e. ETL, EMS and POSE in predicting OCBE among ISO14001-certified Malaysian manufacturing firms.
Analysis of shielding effectiveness and mechanical properties of metal matrix composite AL6061 reinforced with Al2O3 and fly ash for oblique incidence of EM wave
Authors: Budumuru Srinu , Mosa Satya Anuradha
Published: June 2021

Purpose

Fiber-reinforced polymers (FRP) contain critical electrical conductivity for high-intensity radiated fields such as lightning strike susceptibility, electromagnetic energy from radar, airborne radio frequency transmitter. To provide high-intensity radiated field protection (HIRFP) for the electric and electronic aircraft system and defied the EMI effect on it, metal matrix composite was conquered. To provide the dynamic ever-increasing requirement of industries, it is necessary that Al6061 metal matrix composite assisted with AL2O3 and fly ash is used to construct the aircraft to provide HIRFP. The thickness of the material can be maintained as low as possible to use it as a coating material for the aircraft surface. X-band for oblique incidence is used to measure electromagnetic and mechanical safeguarding properties of composites.

Design/methodology/approach

Day by day, the applications of aerospace are becoming digital and automated. Proper shielding techniques are required to operate digital electronic devices without electromagnetic interference. It leads to a rapid rise in temperature, thermal ablation, delamination, and adverse effects on the electric and electronic aircraft system. Fly ash, a metal matrix material composite AL6061 with different percentages of reinforcement of Al2O3, was contemplated and experimented with for mechanical properties like tensile strength, density and hardness.

Findings

The obtained results compared with adjusted values and an improvement of 0.19, 0.18, 0.14 g/cm3 for density of MMC-1, MMC-2, MMC-3.31, 11 MPa for tensile strength of MMC-1, MMC-2. 24, 27, 23 BHN for hardness of MMC-1, MMC-2, MMC-3. With regard to the shielding effectiveness the results compared with adjusted values and obtained 11.36, 14.56, 19.47 dB better value than it. According to the above results, fabricated MMC’s provide superior results for a defined application like HIRFP(Surface material of aircraft).

Practical implications

It can be used to protect electronic devices under a high-intensity radiated field, mainly in aircraft design to protect from lightning effect.

Originality/value

For a better approximation of the signal toward the practical case, the oblique incidence was considered with a different combination of Al2O3 and fly ash, reinforced to pure AL6061 to get better shielding and mechanical properties.
Psychological impact of the COVID-19 lockdown on Vietnamese community
Authors: Gan Christopher , Anh Dao Le Trang , Nguyen Quang Thi Thieu
Published: June 2021

Purpose

This study investigates the psychological impact of the COVID-19 lockdown on Vietnamese people and examines the factors affecting their psychological well-being during and after the lockdown period.

Design/methodology/approach

Based on the survey answers of 701 Vietnamese respondents, this study explores the psychological impact associated with COVID-19 lockdown in Vietnam. Using a newly developed “mvord” package in R that controls the heterogeneity in error structure of the sample units (Hirk et al., 2020), the study runs multivariate ordinal logistic regression models to examine the determinants of the emotional outcomes.

Findings

The study discloses negative psychological states among the Vietnamese community during and after the lockdown, including boredom, anxiety, sadness, stress, anger, precautionary measures and post-traumatic stress symptoms. Demographic characteristics (male gender, young age, poor-health condition, high educational level, small family size, officers or professionals, using public transport, quarantine experience before the lockdown, non-extended lockdown period and living in rural areas) and various difficulties during lockdown (insufficient information about COVID-19, income loss, having daily-life difficulties and unhappy experiences during lockdown) are related to higher degrees of different psychological symptoms during and after lockdown in Vietnam.

Originality/value

This study identifies the importance of mitigating the detrimental effects of the COVID-19 lockdown on Vietnamese well-being and prepares the Vietnamese government better to handle the public mental issues during future lockdowns.
Understanding the link between IS capabilities and cost performance in services: the mediating role of supplier integration
Authors: Teng Teng , Tsinopoulos Christos
Published: June 2021

Purpose

The purpose of this study is to explore the link between information systems (IS) capabilities, supplier integration and cost performance in the service context. Specifically, it empirically investigates how supplier integration meditates the relationship between three dimensions of IS capabilities and cost performance in service firms.

Design/methodology/approach

A survey of 156 UK service firms was conducted and the data analyzed to determine the role of supplier integration in mediating the effects of IS capabilities on firms' cost performance. The research model was tested using structural equation modeling (SEM), and the neural network model was used to rank the relative influence of significant predictors obtained from SEM.

Findings

The results confirmed that supplier integration fully mediates the effects of information technology (IT) for supply chain activities and flexible IT infrastructure on cost performance and partially mediates the effect of operations manager's IT knowledge on cost performance. The results showed that operations manager's IT knowledge is the strongest predictor of supplier integration.

Originality/value

This study takes a step toward quelling concerns about the business value of IS, contributing to the development and validation of the measurement of IS capabilities in the service operations context. Additionally, it adds to the emerging body of literature linking supplier integration to the operational performance of service firms.
Revisiting the patient–physician relationship under the lens of value co-creation and defensive medicine
Authors: Riotta Sergio , Bruccoleri Manfredi
Published: June 2021

Purpose

This study formulates a new archetypical model that describes and re-interprets the patient–physician relationship from the perspective of two widespread phenomena in the healthcare delivery process: value co-creation (VCC) and defensive medicine (DM).

Design/methodology/approach

Grounded in the existing literature on VCC and DM, the authors designed and conducted 20 in-depth interviews with doctors (and patients) about their past relationships with patients (and doctors). After putting the recorded interviews through qualitative analysis with a three-level coding activity, the authors built an empirically informed model to classify patient–physician relationships.

Findings

The authors identified four archetypes of patient–physician relationships. Each archetype is described along with its representing characteristics and explained in terms of its consequences as they relate to VCC and DM.

Research limitations/implications

This research contributes to the literature on both VCC in healthcare and DM, in addition to the patient–physician's relationship literature.

Practical implications

Being aware of patient–physician relationship mechanics, building long-term relations with patients and investing in service personalization and patient-centred care can effectively mitigate the risks of DM behaviours on one side while increasing the likelihood of VCC actualization on the other.

Originality/value

Although strictly linked to the interactions between patients and doctors, VCC and DM are typically considered disentangled. In this research paper, the authors identified four archetypes of patient–physician relationships in relation to these two phenomena.
Hubert Joly: The new capitalism formula – purpose first, people at the center, then profits
Authors: Leavy Brian
Published: June 2021

Purpose

An interview with Hubert Joly, former CEO of Best Buy. His new book is the articulation of key leadership principles for the next era of capitalism, and how to put them into practice, in both the best and hardest of times.

Design/methodology/approach

Joly believes “Work is a quest for meaning. Maximizing profit does not answer that quest.” His “purpose first” approach enabled the acclaimed turnaround of the company during his 2012-to-2019 tenure

Findings

Best Buy’s purpose was ‘to enrich our customers’ lives through technology.

Practical implications

According to Joly, “When we ask Best Buy employees what drives them, no one ever says ‘shareholder value.’”

Originality/value

Joly is a CEO who believes in and practices the approach that it is critical for leaders to understand what drives the individuals around them–and how it connects to the purpose of the organization. He believes business is fundamentally about purpose, people and human relationships. When common purpose aligns with individual searches for meaning, it can unleash a kind of human magic that results in outstanding performance.
Performance evaluation of newly designed nozzle on abrasive jet machining characteristics of laminated composites
Authors: Balasubramanian M. , Madhu S.
Published: June 2021

Purpose

The purpose of the study is to machine the composites at lower machining time with higher accuracy without causing delamination.

Design/methodology/approach

Abrasive jet machining is the technology appropriate for machining composite materials to obtain good dimensional accuracy without causing de-lamination. The central composite design was followed in deciding the number of experiments to be carried out.

Findings

The influence of abrasive jet machining process parameters on machining time, material removal rate (MRR) and kerf characteristics were investigated. The experimental results proved the newly designed internal threaded nozzle increased MRR, thereby reducing the machining time.

Originality/value

Machining of glass fibre reinforced polymer (GFRP) is one of the challenging tasks given its non-linear and in-homogeneous properties. In this investigation, newly developed threaded and unthreaded nozzles in machining were used for making holes on the GFRP composites.