bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep oncopanel sequencing reveals fixation time- and within block position-dependent quality degradation in FFPE processed samples
Authors:   SEQC2 Oncopanel Sequencing Working Group, Zhang Yifan , Blomquist Thomas M. , Kusko Rebecca , Stetson Daniel , Zhang Zhihong , Yin Lihui , Sebra Robert , Gong Binsheng , LoCoco Jennifer S. , Mittal Vinay K. , Novoradovskaya Natalia , Yeo Ji-Youn , Dominiak Nicole , Hipp Jennifer , Raymond Amelia , Qiu Fujun , Arib Hanane , Smith Melissa L. , Brock Jay E. , Farkas Daniel H. , Craig Daniel J. , Crawford Erin L. , Li Dan , Morrison Tom , Tom Nikola , Xiao Wenzhong , Yang Mary , Mason Christopher E. , Richmond Todd A. , Jones Wendell , Johann Donald J. , Shi Leming , Tong Weida , Willey James C. , Xu Joshua
Published: April 2021

Clinical laboratories routinely use formalin-fixed paraffin-embedded (FFPE) tissue or cell block cytology samples in oncology panel sequencing to identify mutations that can predict patient response to targeted therapy. To understand the technical error due to FFPE processing, a robustly characterized normal cell line was used to create FFPE samples with four different pre-tissue processing formalin fixation times. A total of 96 FFPE sections were then distributed to different laboratories for targeted sequencing analysis by four oncopanels, and variants resulting from technical error were identified. Tissue sections that failed more frequently showed low cellularity, lower than recommended library preparation DNA input, or target sequencing depth. Importantly, sections from block surfaces were more likely to show FFPE-specific errors, akin to “edge effects” seen in histology, and the depth of formalin damage was related to fixation time. To assure reliable results, we recommend avoiding the block surface portion and restricting mutation detection to genomic regions of high confidence.
Metabolic function in aging retina and retinal pigment epithelium remains robust despite vision loss
Authors: Tsantilas Kristine A. , Cleghorn Whitney M. , Bisbach Celia M. , Whitson Jeremy A. , Hass Daniel T. , Robbings Brian M. , Sadilek Martin , Linton Jonathan D. , Rountree Austin M. , Valencia Ana P. , Sweetwyne Mariya T. , Campbell Matthew D. , Zhang Huiliang , Jankowski Connor S.R. , Sweet Ian R. , Marcinek David J. , Rabinovitch Peter S. , Hurley James B.
Published: April 2021

Purpose

Characterize how metabolic function in the murine retina and retinal pigment epithelium-choroid-sclera (eyecup) complex is impacted by natural aging.

Methods

We examined scotopic and photopic visual function of young (3-6 months) and aged (23-26 months) C57Bl/6J mice using electroretinograms (ERGs). Metabolic changes in retina and eyecup explants were characterized by measuring uptake and usage of U-13C-glucose or U-13C-glutamine at different timepoints by gas chromatography-mass spectrometry (GC-MS), measuring oxygen consumption rate (OCR) using a perifusion apparatus, and determining ATP levels with a bioluminescence assay.

Results

Scotopic and photopic ERG responses declined in aged mice. Glucose metabolism, glutamine metabolism, OCR, and ATP pools in retinal explants were mostly unaffected by the age of the mouse. In eyecups, glutamine usage in the Krebs Cycle decreased while glucose metabolism, OCR, and ATP pools remained stable.

Conclusions

Theex vivoapproach in our study to examine aging glucose and glutamine metabolism in retina and RPE showed negligible impact of age on retina and an impairment of glutamine anaplerosis in eyecups. The surprising metabolic stability of these tissuesex vivosuggests age-related metabolic alterations in these tissues may not be intrinsic. Future experiments should focus on determining whether external factors including nutrient supply, oxygen availability, or other structural changes influence ocular metabolismin vivo.
A general approach for stabilizing nanobodies for intracellular expression
Authors: Dingus John , Tang Jonathan C.Y. , Cepko Constance
Published: April 2021

Conventional antibodies and their derived fragments are difficult to deploy against intracellular targets in live cells, due to their bulk and structural complexity. Nanobodies provide an alternative modality, with well documented examples of intracellular expression. Despite their promise as intracellular reagents, there has not been a systematic study of nanobody intracellular expression. Here, we examined intracellular expression of 75 nanobodies from the Protein Data Bank. Surprisingly, a majority of nanobodies were unstable in cells, illustrated by aggregation and clearance. Using comparative analysis and framework mutagenesis, we developed a general approach that stabilized a great majority of originally intracellularly unstable nanobodies, without compromising target-binding function. Additionally, we identified distinct sequence features impacting nanobody intracellular stability, and demonstrated mutationally stabilized nanobody expression in vivo, in the murine retina and inE. coli. This work will allow for standardized nanobody engineering for intracellular applications, potentiating a growing field of intracellular interrogation and intervention.
Genetically Engineered DENV Produces Antigenically Distinct Mature Particles
Authors: Tse Longping V. , Meganck Rita M. , Dong Stephanie , Adams Lily E. , White Laura J. , de Silva Aravinda M. , Baric Ralph S.
Published: April 2021

Maturation of Dengue viruses (DENV) alters the structure, immunity and infectivity of the virion and highly mature particles represent the dominant formin vivo. The production of highly mature virions principally relies on the structure and function of the viral premature protein (prM) and its cleavage by the host protease furin. We developed a reliable clonal cell line which produces single-round mature DENVs without the need for DENV reverse genetics. More importantly, using protein engineering coupled with natural and directed evolution of the prM cleavage site, we engineered genetically stable mature DENVs without comprising viral yield and independent of cell, host, or passage. Using these complementary strategies to regulate maturation, we demonstrate that the resulting mature DENVs are antigenically distinct from their isogenic immature forms. Given the clinical importance of mature DENVs in immunity, our strategy provides a reliable strategy for the production of stable, high-titer mature candidate DENV live virus vaccines, genetically stabilized viruses for DENV maturation and immunity studies, and models for maturation-regulated experimental evolution in mammalian and invertebrate cells. Our data from directed-evolution across host species reveals distinct maturation-dependent selective pressures between mammalian and insect cells, which sheds light on the divergent evolutionary relationship of DENVs between its host and vector.
Caspar, an adapter for VAP and TER94 delays progression of disease by regulating glial inflammation in aDrosophilamodel of ALS8
Authors: Tendulkar Shweta , Hegde Sushmitha , Thulasidharan Aparna , Garg Lovleen , Kaduskar Bhagyashree , Ratnaparkhi Anuradha , Ratnaparkhi Girish S
Published: April 2021

Amyotrophic Lateral Sclerosis (ALS) is a fatal, late onset, progressive motor neurodegenerative disorder. We have been studying cellular and molecular mechanisms involved in ALS using a vesicle-associated membrane protein-associated protein B (VAPB/ALS8)Drosophilamodel, which mimics many systemic aspects of the human disease. Here, we show that the ER resident VAPB interacts with Caspar, an ortholog of human fas associated factor 1 (FAF1). Caspar, in turn, interacts with transitional endoplasmic reticulum ATPase (TER94), a fly ortholog of ALS14 (VCP/p97, Valosin-containing protein), via its UBX domain and poly-ubiqutinated proteins with its UBA domain. Caspar overexpression in the glia extends lifespan and also slows the progression of motor dysfunction in the ALS8 model, a phenomenon that we ascribe to its ability to restrain age-dependant inflammation, modulated by Relish/NFκB signalling.

We hypothesize that Caspar is a key molecule in the pathogenesis of ALS. Caspar connects the plasma membrane (PM) localized immune signalosome to the ER based VAPB degradative machinery, presumably at PM:ER contact sites. The Caspar:TER94:VAPB complex appears to be a strong candidate for regulating both protein homeostasis and NFκB signalling. These, in turn, regulate glial inflammation and determine progression of disease. Our study projects human FAF1 as an important protein target to alleviate the progression of motor neuron disease.
Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp3 Papain-like Protease
Authors: Lim Chew Theng , Tan Kang Wei , Wu Mary , Ulferts Rachel , Armstrong Lee A. , Ozono Eiko , Drury Lucy S. , Milligan Jennifer C. , Zeisner Theresa U. , Zeng Jingkun , Weissmann Florian , Canal Berta , Bineva-Todd Ganka , Howell Michael , O’Reilly Nicola , Beale Rupert , Kulathu Yogesh , Labib Karim , Diffley John F.X
Published: April 2021

The COVID-19 pandemic has emerged as the biggest life-threatening disease of this century. Whilst vaccination should provide a long-term solution, this is pitted against the constant threat of mutations in the virus rendering the current vaccines less effective. Consequently, small molecule antiviral agents would be extremely useful to complement the vaccination program. The causative agent of COVID-19 is a novel coronavirus, SARS-CoV-2, which encodes at least nine enzymatic activities that all have drug targeting potential. The papain-like protease (PLpro) contained in the nsp3 protein generates viral non-structural proteins from a polyprotein precursor, and cleaves ubiquitin and ISG protein conjugates. Here we describe the expression and purification of PLpro. We developed a protease assay that was used to screen a custom chemical library from which we identified Dihydrotanshinone I and Ro 08-2750 as compounds that inhibit PLpro in protease and isopeptidase assays and also inhibit viral replication in cell culture-based assays.
Identification of SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of the nsp14 RNA Cap Methyltransferase
Authors: Basu Souradeep , Mak Tiffany , Ulferts Rachel , Wu Mary , Deegan Tom , Fujisawa Ryo , Tan Kang Wei , Lim Chew Theng , Basier Clovis , Canal Berta , Curran Joseph F. , Drury Lucy , McClure Allison W. , Roberts Emma L. , Weissmann Florian , Zeisner Theresa U. , Beale Rupert , Cowling Victoria H. , Howell Michael , Labib Karim , Diffley John F.X.
Published: April 2021

The COVID-19 pandemic has presented itself as one of the most critical public health challenges of the century, with SARS-CoV-2 being the third member of theCoronaviridaefamily to cause fatal disease in humans. There is currently only one antiviral compound, remdesivir, that can be used for the treatment of COVID-19. In order to identify additional potential therapeutics, we investigated the enzymatic proteins encoded in the SARS-CoV-2 genome. In this study, we focussed on the viral RNA cap methyltransferases, which play a key role in enabling viral protein translation and facilitating viral escape from the immune system. We expressed and purified both the guanine-N7 methyltransferase nsp14, and the nsp16 2’-O-methyltransferase with its activating cofactor, nsp10. We performed anin vitrohigh-throughput screen for inhibitors of nsp14 using a custom compound library of over 5,000 pharmaceutical compounds that have previously been characterised in either clinical or basic research. We identified 4 compounds as potential inhibitors of nsp14, all of which also show antiviral capacity in a cell based model of SARS-CoV-2 infection. Three of the 4 compounds also exhibited synergistic effects on viral replication with remdesivir.
Consolidation of human skill linked to waking hippocampo-neocortical replay
Authors: Buch ER , Claudino L , Quentin R , Bönstrup M , Cohen LG
Published: April 2021

The introduction of rest intervals interspersed with practice strengthens wakeful consolidation of skill. The mechanisms by which the brain binds discrete action representations into consolidated, highly temporally-resolved skill sequences during waking rest are not known. To address this question, we recorded magnetoencephalography (MEG) during acquisition and rapid consolidation of a sequential motor skill. We report the presence of highly prominent, fast waking neural replay during the same rest periods in which rapid consolidation occurs. The observed replay was temporally compressed by approximately 20x relative to the acquired skill, occurred in both forward and reverse directions, was selective for the trained sequence and predicted the magnitude of skill consolidation. Replay representations extended beyond the hippocampus and entrorhinal cortex to the contralateral sensorimotor cortex. These results document the presence of robust hippocampo-neocortical replay supporting rapid wakeful consolidation of skill.
Comparable environmental stability and disinfection profiles of the currently circulating SARS-CoV-2 variants of concern B.1.1.7 and B.1.351
Authors: Meister Toni Luise , Fortmann Jil , Todt Daniel , Heinen Natalie , Ludwig Alfred , Brueggemann Yannick , Elsner Carina , Dittmer Ulf , Pfaender Stephanie , Steinmann Eike
Published: April 2021

The emergence of novel SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern with increased transmission dynamics has raised questions regarding stability and disinfection of these viruses. In this study, we analyzed surface stability and disinfection of the currently circulating SARS-CoV-2 variants B.1.1.7 and B.1.351 compared to the wildtype. Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks. Overall, our data support the application of currently recommended hygiene concepts to minimize the risk of B.1.1.7 and B.1.351 transmission.
APOE ε4allele advances the age-dependent decline of amyloid β clearance in the human cortex
Authors: Saito Atsushi , Kageyama Yusuke , Pletnikova Olga , Rudow Gay L. , An Yang , Irie Yumi , Kita Akiko , Miki Kunio , Li Ling , Southall Pamela , Irie Kazuhiro , Troncoso Juan C.
Published: April 2021

Introduction

Our previous study indicated that the pericapillary clearance of amyloid β (Aβ) declines with age inAPOE 3/3subjects. Here, we examine whether theAPOEε4allele has an impact on this age-related decline.

Methods

We examined 69 autopsy brains ofAPOEε3/ε4orAPOEε3/ε3individuals (30-65 years) for the immunohistochemical localization of intracellular, extracellular, and pericapillary Aβ in the cerebral cortex.

Results

InAPOEε3/ε4individuals, the percentage of Aβ positive pericapillary spaces began to decrease (p=0.030), and the number of extracellular Aβ particles increased in the early 30s (p=0.0008). Those average values were significantly lower (p<0.0001) and higher (p<0.0001), respectively, compared toAPOEε3/ε3individuals.

Discussion

Our observations indicate thatAPOEε4allele advances by one decade at the onset of age-related decline in Aβ glymphatic clearance. This finding supports early clinical intervention and stratification by APOE genotype to prevent Aβ deposition and AD progression.
CLCd and CLCf act redundantly at the TGN/EE and prevent acidification of the Golgi stack
Authors: Scholl Stefan , Hilmer Stefan , Krebs Melanie , Schumacher Karin
Published: April 2021

The trans-Golgi network/early endosome (TGN/EE) serves as the central hub in which exo- and endocytic trafficking pathways converge and specificity of cargo routing needs to be achieved. Acidification is a hallmark of the TGN/EE and is maintained by the vacuolar H+-ATPase (V-ATPase) with support of proton-coupled antiporters. We show here that CLCd and CLCf, two distantly related members of the Arabidopsis chloride channel (CLC)-family that colocalize in the TGN/EE act redundantly and are essential for male gametophyte development. Combining an inducible knock-down approach and in vivo pH-measurements, we show here that reduced CLC-activity does not affect pH in the TGN/EE but causes accumulation of the V-ATPase in trans-Golgi cisternae leading to their hyper-acidification. Taken together, our results show that CLC-mediated anion transport into the TGN/EE is essential and affects spatio-temporal aspects of TGN/EE-maturation as well as its functional separation from the Golgi stack.
Autism risk gene POGZ promotes chromatin accessibility and expression of clustered synaptic genes
Authors: Markenscoff-Papadimitriou Eirene , Binyameen Fadya , Whalen Sean , Price James , Lim Kenneth , Catta-Preta Rinaldo , Pai Emily Ling-Lin , Mu Xin , Xu Duan , Pollard Katherine S. , Nord Alex , State Matthew W. , Rubenstein John L.
Published: April 2021

De novomutations inPOGZ, which encodes the chromatin regulatorPogoTransposable Element with ZNF Domain protein, are strongly associated with autism spectrum disorder (ASD). Here we find that in the developing mouse and human brain POGZ binds predominantly euchromatic loci and these are enriched for human neurodevelopmental disorder genes and transposable elements. We profile chromatin accessibility and gene expression inPogz−/−mice and find that POGZ promotes chromatin accessibility of candidate regulatory elements (REs) and the expression of clustered synaptic genes. We further demonstrate that POGZ forms a nuclear complex and co-occupies loci with HP1γ and ADNP, another high-confidence ASD risk gene. InPogz+/−mice,Adnpexpression is reduced. We postulate that reduced POGZ dosage disrupts cortical function through alterations in the POGZ-ADNP balance which modifies neuronal gene expression.
Regulation of Interorganellar Ca2+Transfer and NFAT Activation by the Mitochondrial Ca2+Uniporter
Authors: Yoast Ryan E. , Emrich Scott M. , Zhang Xuexin , Xin Ping , Arige Vikas , Pathak Trayambak , Benson J. Cory , Johnson Martin T. , Lakomski Natalia , Hempel Nadine , Han Jung Min , Dupont Geneviève , Yule David I. , Sneyd James , Trebak Mohamed
Published: April 2021

Mitochondrial Ca2+uptake is crucial for coupling receptor stimulation to cellular bioenergetics. Further, Ca2+uptake by respiring mitochondria prevents Ca2+-dependent inactivation (CDI) of store-operated Ca2+release-activated Ca2+(CRAC) channels and inhibits Ca2+extrusion to sustain cytosolic Ca2+signaling. However, how Ca2+uptake by the mitochondrial Ca2+uniporter (MCU) shapes receptor-evoked interorganellar Ca2+signaling is unknown. Here, we generated several cell lines with MCU-knockout (MCU-KO) as well as tissue-specific MCU-knockdown mice. We show that mitochondrial depolarization, but not MCU-KO, inhibits store-operated Ca2+entry (SOCE). Paradoxically, despite enhancing Ca2+extrusion and promoting CRAC channel CDI, MCU-KO increased cytosolic Ca2+in response to store depletion. Further, physiological agonist stimulation in MCU-KO cells led to enhanced frequency of cytosolic Ca2+oscillations, endoplasmic reticulum Ca2+refilling, NFAT nuclear translocation and proliferation. However, MCU-KO did not affect inositol-1,4,5-trisphosphate receptor activity. Mathematical modeling supports that MCU-KO enhances cytosolic Ca2+, despite limiting CRAC channel activity.
Safe and effective pool testing for SARS-CoV-2 detection
Authors: Wunsch Marie , Aschemeier Dominik , Heger Eva , Ehrentraut Denise , Krüger Jan , Hufbauer Martin , Syed Adnan S. , Horemheb-Rubio Gibran , Dewald Felix , Fish Irina , Schlotz Maike , Gruell Henning , Augustin Max , Lehmann Clara , Kaiser Rolf , Knops Elena , Silling Steffi , Klein Florian
Published: April 2021

Background / Objectives

The global spread of SARS-CoV-2 is a serious public health issue. Large-scale surveillance screenings are crucial but can exceed diagnostic test capacities. We set out to optimize test conditions and implemented high throughput pool testing of respiratory swabs into SARS-CoV-2 diagnostics.

Study design

In preparation for pool testing, we determined the optimal pooling strategy and pool size. In addition, we measured the impact of vortexing prior to sample processing, compared pipette- and swab-pooling method as well as the sensitivity of three different PCR assays.

Results

Using optimized strategies for pooling, we systematically pooled 55,690 samples in a period of 44 weeks resulting in a reduction of 47,369 PCR reactions. In a low prevalence setting, we defined a preferable pool size of ten in a two-stage hierarchical pool testing strategy. Vortexing of the swabs increased cellular yield by a factor of 2.34, and sampling at or shortly after symptom onset was associated with higher viral loads. By comparing different pooling strategies, pipette-pooling was more efficient compared to swab-pooling.

Conclusions

For implementing pooling strategies into high throughput diagnostics, we recommend to apply a pipette-pooling method, using pool sizes of ten samples, performing sensitivity validation of the PCR assays used, and vortexing swabs prior to analyses. Our data shows, that pool testing for SARS-CoV-2 detection is feasible and highly effective in a low prevalence setting.
Heterogenous impairment of α-cell function in type 2 diabetes is linked to cell maturation state
Authors: Dai Xiao-Qing , Camunas-Soler Joan , Briant Linford JB , Santos Theodore dos , Spigelman Aliya F , Walker Emily M. , Arrojo e Drigo Rafael , Bautista Austin , Jones Robert C. , Lyon James , Nie Aifang , Smith Nancy , Fox Jocelyn E Manning , Kim Seung K , Rorsman Patrik , Stein Roland W , Quake Stephen R , MacDonald Patrick E
Published: April 2021

In diabetes, glucagon secretion from pancreatic α-cells is dysregulated. We examined α-cells from human donors and mice using combined electrophysiological, transcriptomic, and computational approaches. Rising glucose suppresses α-cell exocytosis by reducing P/Q-type Ca2+channel activity, and this is disrupted in type 2 diabetes (T2D). Upon high-fat-feeding of mice, α-cells shift towards a ‘β-cell-like’ electrophysiologic profile in concert with an up-regulation of the β-cell Na+channel isoformScn9aand indications of impaired α-cell identity. In human α-cells we identify links between cell membrane properties and cell surface signalling receptors, mitochondrial respiratory complex assembly, and cell maturation. Cell type classification using machine learning of electrophysiology data demonstrates a heterogenous loss of ‘electrophysiologic identity’ in α-cells from donors with T2D. Indeed, a sub-set of α-cells with impaired exocytosis is defined by an enrichment in progenitor markers suggesting important links between α-cell maturation state and dysfunction in T2D.

Key findings

α-cell exocytosis is suppressed by glucose-dependent inhibition of P/Q-type Ca2+currents

Dysfunction of α-cells in type 2 diabetes is associated with a ‘β-cell-like’ electrophysiologic signature

Patch-seq links maturation state, the mitochondrial respiratory chain, and cell surface receptor expression to α-cell function

α-cell dysfunction occurs preferentially in cells enriched in endocrine lineage markers
Protective host-dependent antagonism amongPseudomonasin theArabidopsisphyllosphere
Authors: Shalev Or , Karasov Talia L. , Lundberg Derek S. , Ashkenazy Haim , Weigel Detlef
Published: April 2021

The plant microbiome is a rich biotic environment, comprising numerous taxa. The community structure of these colonizers is constrained by multiple factors, including host-microbe and microbe-microbe interactions, as well as the interplay between the two. While much can be learned from pairwise relationships between individual hosts and microbes, or individual microbes with themselves, the ensemble of interrelations between the host and microbial consortia may lead to different outcomes that are not easily predicted from the individual interactions. Their study can thus provide new insights into the complex relationship between plants and microbes. Of particular importance is how strain-specific such plant-microbe-microbe interactions are, and how they eventually affect plant health. Here, we test strain-level interactions in the phyllosphere between groups of co-existing commensal and pathogenicPseudomonasamong each other and withA. thaliana, by employing synthetic communities of genome-barcoded isolates. We found that commensalPseudomonasprompted a host response leading to a selective inhibition of a specific pathogenic lineage, resulting in plant protection. The extent of plant protection, however, was dependent on plant genotype, indicating that these effects are host-mediated. There were similar genotype-specific effects on the microbe side, as we could pinpoint an individualPseudomonasisolate as the predominant cause for this differential interaction. Collectively, our work highlights how within-species genetic differences on both the host and microbe side can have profound effects on host-microbe-microbe dynamics. The paradigm that we have established provides a platform for the study of host-dependent microbe-microbe competition and cooperation in theA. thaliana-Pseudomonassystem.
Tracking pre-mRNA maturation across subcellular compartments identifies developmental gene regulation through intron retention and nuclear anchoring
Authors: Yeom Kyu-Hyeon , Pan Zhicheng , Lin Chia-Ho , Lim Han Young , Xiao Wen , Xing Yi , Black Douglas L.
Published: April 2021

Steps of mRNA maturation are important gene regulatory events that occur in distinct cellular locations. However, transcriptomic analyses often lose information on the subcellular distribution of processed and unprocessed transcripts. We generated extensive RNA-seq data sets to track mRNA maturation across subcellular locations in mouse embryonic stem cells, neuronal progenitor cells, and postmitotic neurons. We find disparate patterns of RNA enrichment between the cytoplasmic, nucleoplasmic, and chromatin fractions, with some genes maintaining more polyadenylated RNA in chromatin than in the cytoplasm. We bioinformatically defined four regulatory groups for intron retention, including complete cotranscriptional splicing, complete intron retention in the cytoplasmic RNA, and two intron groups present in nuclear and chromatin transcripts but fully excised in cytoplasm. We found that introns switch their regulatory group between cell types, including neuronally excised introns repressed by polypyrimidine track binding protein 1 (PTBP1). Transcripts for the neuronal gamma-aminobutyric acid (GABA) B receptor, 1 (Gabbr1) are highly expressed in mESCs but are absent from the cytoplasm. Instead, incompletely spliced Gabbr1 RNA remains sequestered on chromatin, where it is bound by PTBP1, similar to certain long noncoding RNAs. Upon neuronal differentiation, Gabbr1 RNA becomes fully processed and exported for translation. Thus, splicing repression and chromatin anchoring of RNA combine to allow posttranscriptional regulation of Gabbr1 over development. For this and other genes, polyadenylated RNA abundance does not indicate functional gene expression. Our data sets provide a rich resource for analyzing many other aspects of mRNA maturation in subcellular locations and across development.
Stakeholders’ views on effective employment support strategies for autistic university students and graduates entering the world of work
Authors: Pesonen Henri , Waltz Mitzi , Fabri Marc , Syurina Elena , Krückels Sarah , Algner Mona , Monthubert Bertrand , Lorenz Timo
Published: April 2021

Purpose

This paper aims to examine effective support strategies for facilitating the employment of autistic students and graduates by answering the following research question: What constitutes effective employment support for autistic students and graduates?

Design/methodology/approach

Data were collected using the method of empathy-based stories (MEBS) as part of a multinational European project’s Web-based survey. The data consisted of 55 writings about effective strategies and 55 writings about strategies to ]avoid when working with autistic students and graduates. The material was analysed using qualitative inductive content analysis. Narratives were created to illustrate desirable and undesirable environments and processes as they would be experienced by students, supported by original excerpts from the stories.

Findings

The analysis revealed that effective employment support for autistic students and graduates comprised three dimensions of support activity: practices based on the form and environment of support, social interaction support and autism acceptance and awareness. These dimensions were present in both recommended and not recommended support strategy writings.

Originality/value

The results add to the literature on autism and employment with its focus on the novel context of autistic university students and graduates. Effective strategies will be based on person-centred planning, to include not only the individual impact of autism but also individual career goals, workplace characteristics in the chosen field, employer needs and allocation of the right support. There is no one-size-fits-all strategy, but rather an individualized process is needed, focused on the identification of strengths, the adaptation of employment and work processes and improved understanding and acceptance of autism by management, colleagues and administration in the workplace.
An assessment tool for the evaluation of circular economy implementation
Authors: Diéguez-Santana Karel , Rodríguez Rudi Giselle , Acevedo Urquiaga Ana Julia , Muñoz Emanuel , Sablón-Cossio Neyfe
Published: April 2021

Purpose

In this paper, the authors adopt the theory of the circular economy to study the transitions that take place in three case studies in Mexico and Ecuador. The work is aimed to systematize a circular economy assessment tool that fosters opportunities for improvement in business practices.

Design/methodology/approach

The methodology is based on a descriptive quantitative analysis, where a checklist is made with 91 items and nine study variables. This is from the study of the bibliography and business practice. Furthermore, the neural network method is used in a case study to predict the level of circular economy and the importance of each variable according to the sensitivity by the Lek’s profile method.

Findings

It is based on a descriptive quantitative analysis, where a checklist with 91 items and nine study variables is made, defined from a bibliographic study and business practice. Furthermore, the neural network method is used in a case study to predict the level of circular economy and the importance of each variable based on sensitivity.

Research limitations/implications

The application of the tool requires prior knowledge of the circular economy approach, which is why specialized personnel are needed for its application. This makes research more expensive in time and human resources.

Practical implications

The practical and methodological contribution of this work lies in the feasibility of the tool that favors the definition of improvement actions for the implementation contribution to the circular economy in business practices.

Social implications

The social contribution is framed in the gradual transition to circular economy approaches in underdeveloped countries.

Originality/value

The use of the neural network method to predict the level of circular economy in a case study allows making decisions in a predictive way. This encourages the development of the circular economy according to the context needs.
A systematic identification approach for biaxial piezoelectric stage with coupled Duhem-type hysteresis
Authors: Chen Qun , Yang Zong-Xiao , Fu Zhumu
Published: April 2021

Purpose

The problem of parameter identification for biaxial piezoelectric stages is still a challenging task because of the existing hysteresis, dynamics and cross-axis coupling. This study aims to find an accurate and systematic approach to tackle this problem.

Design/methodology/approach

First, a dual-input and dual-output (DIDO) model with Duhem-type hysteresis is proposed to depict the dynamic behavior of the biaxial piezoelectric stage. Then, a systematic identification approach based on a modified differential evolution (DE) algorithm is proposed to identify the unknown parameters of the Duhem-type DIDO model for a biaxial piezostage. The randomness and parallelism of the modified DE algorithm guarantee its high efficiency.

Findings

The experimental results show that the characteristics of the biaxial piezoelectric stage can be identified with adequate accuracy based on the input–output data, and the peak-valley errors account for 2.8% of the full range in the X direction and 1.5% in the Y direction. The attained results validated the correctness and effectiveness of the presented identification method.

Originality/value

The classical DE algorithm has many adjustment parameters, which increases the inconvenience and difficulty of using in practice. The parameter identification of Duhem-type DIDO piezoelectric model is rarely studied in detail and its successful application based on DE algorithm on a biaxial piezostage is hitherto unexplored. To close this gap, this work proposed a modified DE-based systematic identification approach. It not only can identify this complicated model with more parameters, but also has little tuning parameters and thus is easy to use.
Mobike China: competing through the giant’s ecosystem
Authors: Kittilaksanawong Wiboon , Liu Huijing
Published: April 2021

Learning outcomes

Students will be able to analyse competitive situations of the focal firm in the platform market, factors that make the focal firm become dominant in the sharing economy through the technology platform and the focal firm’s motives and growth strategies through mergers and acquisitions and overseas expansion, as well as give recommendations on the focal firm’s strategies to move forward to achieve and maintain its competitive position in the platform market.

Case overview/synopsis

On 4th April, 2018, Meituan-Dianping (Meituan), a Chinese group-buying website for consumer products and retail services acquired Mobike, a Chinese dockless bike-sharing platform for US$2.7bn. Mobike had raised several rounds of funding for its large investments and operations in this highly competitive and cash-intensive industry. However, it was still struggling to survive and make a profit in the Chinese and overseas markets. It was believed that the merger between the companies was the only viable alternative. Had Meituan’s Chief Executive Officer made the right decision in acquiring Mobike? After Mobike became an integral part of Meituan, what should be done to turn this technology platform to be profitable in the Chinese and overseas market?

Complexity academic level

The case is intended for senior undergraduate or graduate-level courses in business schools.

Supplementary materials

Teaching Notes are available for educators only.

Subject code

CSS 11: Strategy.
Exploring readiness of learners to transfer training: an interactionist approach
Authors: Ragini  , Ghosh Piyali
Published: April 2021

Purpose

Purpose of this study is to investigate the role of learner readiness in enhancing transfer of training by empirically testing a moderated mediation mechanism in which learner readiness influences transfer through motivation to transfer, and this indirect impact is moderated by supervisor support.

Design/methodology/approach

The perception of trainees about the constructs considered has been captured through a survey of 250 employees of a unit of a manufacturing organization in India. For hypotheses testing, PROCESS macro developed by Hayes (2013) has been used.

Findings

Results have confirmed the significant role played by learner readiness in predicting transfer. This apart, supervisor support has been proved to moderate the indirect impact of learner readiness on transfer.

Practical implications

Trainees need to have pre-requisite knowledge to learn the content of a training programme, which would enable them to grasp such content and transfer the same subsequently to work. It is also essential that trainees are willing to attend any training voluntarily. Specific interventions may be designed for supervisors to bolster their catalytic role in training transfer.

Originality/value

An interactionist approach has been adopted by focussing on learner readiness as a less-studied trainee characteristic and supervisor support as a situational factor of transfer. This is construed as a significant contribution of this study to training literature. The potential overlap between learner readiness and motivation to transfer as trainee characteristics is seen to be neutralized by the presence of supervisor support as a moderator. Findings help in understanding how a trainee’s readiness and motivation, together with supervisor’s positive attitude, can enhance transfer.
The role of human environment in making a workplace congenial: a case of university libraries
Authors: Saleem Qurat Ul Ain , Ameen Kanwal
Published: April 2021

Purpose

Organizations ought to provide a congenial workplace for employees, particularly females, to get optimum performance. This study aims to investigate the congeniality of libraries’ human environment for female library and information science professionals (LIPs). Regarding the human environment, the manager’s support, relationship with colleagues and informal communication have been studied.

Design/methodology/approach

For this quantitative study, the researchers use a survey research method based on a self-constructed questionnaire. The questionnaire consisted of closed-ended questions, which were used to collect the data; however, the open-ended question entitled comments was also added to take the opinion of respondents. The sampling includes the female LIPs working in the university libraries of Punjab, Pakistan.

Findings

The results highlight that female LIPs were satisfied with the human environment at their workplaces. Participants not only appreciated the role and support of their immediate managers in terms of respect, feedback, task allocation and approachability but also recognized the role of colleagues and informal communication (social interaction) in making their workplace congenial and comfortable to work by establishing a positive relationship with supervisors, colleagues or subordinates at the workplace. However, some open-ended comments reveal that females face leg-pulling, favoritism, male colleagues’ indecent behavior and managers’ critical behavior at the workplace.

Research limitations/implications

Because of the sensitivity of the topic and limitedness of an instrument, the respondents might have been hesitant to give real opinions. This study was limited in terms of participants as data was collected only from one province of Pakistan.

Practical implications

Workplaces for females in a male-dominated society like Pakistan impede their commitment to giving their best. Despite an increased number of females in the profession, it is surprising that so little empirical research has been conducted on the topic. Therefore, this study is an excellent addition to the dearth of literature on the subject. The findings may help in sensitizing the management and authorities to control the human environment at workplaces as this study will also bring into light the prevailing working environment for females.

Originality/value

Libraries as a workplace have been studied internationally (Farler and Broady-Preston, 2012; Ocholla, 2002; Oud, 2008). From the local perspective, the only study concerning the workplace issues of libraries is by Yousafet al.(2013), which was limited to the managerial problems faced by female librarians working at the University of the Punjab. Hence, to the best of the authors’ knowledge, this study will be one of its nature.
Archival Big Data and the Spanish Flu in Copenhagen
Authors: Abildgren Kim
Published: April 2021

Purpose

The Spanish Flu 1918–1920 saw a high degree of excess mortality among young and healthy adults. The purpose of this paper is a further exploration of the hypothesis that high mortality risk during The Spanish Flu in Copenhagen was associated with early life exposure to The Russian Flu 1889–1892.

Design/methodology/approach

Based on 37,000 individual-level death records in a new unique database from The Copenhagen City Archives combined with approximate cohort-specific population totals interpolated from official censuses of population, the author compiles monthly time series on all-cause mortality rates 1916–1922 in Copenhagen by gender and one-year birth cohorts. The author then analyses birth cohort effects on mortality risk during The Spanish Flu using regression analysis.

Findings

The author finds support for hypotheses relating early life exposure to The Russian Flu to mortality risk during The Spanish Flu. Some indications of possible gender heterogeneity during the first wave of The Spanish Flu – not found in previous studies – should be a topic for future research based on data from other countries.

Originality/value

Due to lack of individual-level death records with exact dates of birth and death, previous studies on The Spanish Flu in Denmark and many other countries have relied on data with lower birth cohort resolutions than the one-year birth cohorts used in this study. The analysis in this paper illustrates how archival Big Data can be used to gain new insights in studies on historical pandemics.
Success and failure factors in implementing quality management systems in small- and medium-sized enterprises: a mixed-method study
Authors: Mehrabioun Mohammadi Mohammad , Jalali Ali , Hasani Arezoo
Published: April 2021

Purpose

This manuscript concentrates on addressing the success and failure factors to satisfy the small- and medium-sized enterprises (SMEs) need when facing challenges during the implementation of the quality management systems (QMSs) such as lack of both the financial and human resources and inadequate technical knowledge of quality management and employee indifference.

Design/methodology/approach

This research employs a mixed-method research approach in three different steps. First, based on interviews and a review of previous research, a list of critical factors influencing the success and failure of QMS implementation in SMEs is provided. After conducting the interview and extracting the results, a quantitative questionnaire is recruited as a complementary tool to demonstrate the accuracy of the literature review and interview findings and to increase the validity and reliability of the data. By applying the exploratory factor analysis (EFA) method, the factors affecting the failure and success of QMS implementation are identified separately. In the third step, a focus group meeting is used to name the factors and identify the relationships among them. The relationships among the factors are also shown using the concept map. Finally, after conducting the focus group meeting, several key issues have been extracted from practice and literature to realize the critical success and failure factors.

Findings

The current study reveals that the factors supporting the SMEs during the implementation of the QMSs may be classified into nine groups. Of these, six factors are related to critical success factors (CSFs), and three factors are related to critical failure factors (CFFs).

Originality/value

There have been several studies developed and conducted to address the success factors supporting the QMSs in SMEs. However, the scope of these studies has only been set on either qualitative or quantitative approaches. Hence, the proposed method presented in this essay, which is, in turn, a new contribution, attempts to use a combined approach based on both the semistructured interviews and survey methods. The results of this study can be used as a reference by scholars and practitioners to identify the relevant issues of QMSs and their application in SMEs.
The role of knowledge diffusion in evolving governance principles for Islamic banking
Authors: Malik Adnan , Ullah Karim , Jan Shafiullah , Atiq Muhammad , Abdullah Ali
Published: April 2021

Purpose

This study aims to describe the role of knowledge diffusion in evolving governance principles for Islamic banking.

Design/methodology/approach

This study develops a discursive theoretical debate using the discourse analysis method on the Sharīʿah principles related to interest (Riba), excessive uncertainty (Gharrar) and profit and loss sharing and their convergence with the conventional banking principles of profitability, solvency and liquidity.

Findings

The study proposes a novel framework that describes how knowledge diffusion bridge-up the Sharīʿah and banking principles in terms of integration of banking principles by Sharīʿah scholars, integration of Sharīʿah principles by managers and the resultant, emergent principles for the governance of Islamic banking.

Practical implications

The proposed framework can inform professionals on how knowledge of banking practices and Sharīʿah can help them in governing Islamic banking. The Board of Directors may adopt a holistic approach for encouraging enhanced interactions between Sharīʿah scholars and managers. Such interaction may be increasing harmony, reducing conflicts and better coordination resulting in Sharīʿah-compliant and market wise viable products and services, thus increasing banking profitability.

Originality/value

This is the first study, which acknowledges and illustrates the role of the knowledge diffusion process in evolving governance principles for Islamic banks. This paper contributes to the theory of corporate governance by using the knowledge, aptitude and practice theory lens to examine conceptually how Islamic banking governance principles emerged through the knowledge diffusion process.
Depiction of possible solutions to improve the cold supply chain performance system
Authors: Kumar Neeraj , Tyagi Mohit , Sachdeva Anish
Published: April 2021

Purpose

A poor performance of the cold supply chain (CSC) may increase the loss of quality and potency of perishables and temperature-sensitive products that deteriorate the financial and environmental aspects of the same. The purpose of the current research work is to identify the critical performance factors (criteria) and their co-factors (sub-criteria) that are responsible for the performance measurement of CSC and suggest the best possible solutions (alternatives) to improve the same.

Design/methodology/approach

To achieve the objective of the research, a hierarchical model has been developed and analyzed using Analytic Hierarchy Process (AHP)-Fuzzy TOPSIS as a hybrid approach to obtain the severity weights of the identified criteria and prioritization toward their relative importance for the best possible alternatives.

Findings

Analysis reveals that the criteria “energy consumption” comes out to be the most critical criteria, and alternative “application of passive cold devices” is the most effective solution for improving the performance of CSC. Higher energy consumption leads to a higher rate of greenhouse gas (GHG) emissions increasing the global warming phenomenon, high operational cost and degradation of natural energy resources. The Application of Passive Cold Devices (PCDs) utilizes solar energy to operate the refrigeration units reducing the energy consumption, environmental and operating cost of CSC.

Research limitations/implications

The research work provides several insights into the critical issues related to the CSC and suggests significant findings that enable the management and decision-makers to adopt these practices for performance evaluation and improvement of the same. The key findings of the work, such as “application of passive cold devices” and “application of IoT in cold chain logistics”, facilitate an improved platform to improve the CSC performance and proposed several directions that will enhance the merit of future research.

Originality/value

The presented study consolidates the various perspectives associated with CSC performance, explores the most critical criteria and proposes the best suitable cold chain practices for organizational growth. The work also provides an analytical analysis with the essence of practicalities and sensitivity analysis to support the robustness of the results. By enriching the literature and quantitative analysis of the new proposed model, this paper forms vast managerial and research implications in the field of CSC.