bluuebunny/crossref_metadata_2025 huggingface dataset:
Copy number signatures predict chromothripsis and associate with poor clinical outcomes in patients with newly diagnosed multiple myeloma
Authors: Maclachlan Kylee H , Rustad Even H , Derkach Andriy , Zheng-Lin Binbin , Yellapantula Venkata , Diamond Benjamin , Hultcrantz Malin , Ziccheddu Bachisio , Boyle Eileen , Blaney Patrick , Bolli Niccolò , Zhang Yanming , Dogan Ahmet , Lesokhin Alexander , Morgan Gareth , Landgren Ola , Maura Francesco
Published: November 2020

Chromothripsis is detectable in 20-30% of newly diagnosed multiple myeloma (NDMM) patients and is emerging as a new independent adverse prognostic factor. In this study, we interrogate 752 NDMM patients using whole genome sequencing (WGS) to study the relationship of copy number (CN) signatures to chromothripsis and show they are highly associated. CN signatures are highly predictive of the presence of chromothripsis (AUC=0.90) and can be used to identify its adverse prognostic impact. The ability of CN signatures to predict the presence of chromothripsis was confirmed in a validation series of WGS comprised of 235 hematological cancers (AUC=0.97) and an independent series of 34 NDMM (AUC=0.87). We show that CN signatures can also be derived from whole exome data (WES) and using 677 cases from the same series of NDMM, we were able to predict both the presence of chromothripsis (AUC=0.82) and its adverse prognostic impact. CN signatures constitute a flexible tool to identify the presence of chromothripsis and is applicable to WES and WGS data.
Disease specific alterations in the olfactory mucosa of patients with Alzheimer’s disease
Authors: Lampinen Riikka , Fazaludeen Mohammad Feroze , Avesani Simone , Örd Tiit , Penttilä Elina , Lehtola Juha-Matti , Saari Toni , Hannonen Sanna , Saveleva Liudmila , Kaartinen Emma , Acosta Francisco Fernandez , Cruz-Haces Marcela , Löppönen Heikki , Mackay-Sim Alan , Malm Tarja , Kaikkonen Minna U , Koivisto Anne M , White Anthony R , Giugno Rosalba , Chew Sweelin , Kanninen Katja M
Published: November 2020

Olfactory dysfunction manifests early in several neurodegenerative disorders. Olfaction is orchestrated by olfactory mucosal cells located in the upper nasal cavity. However, it is unclear how this tissue reflects key neurodegenerative features in Alzheimer’s disease. Here we report that Alzheimer’s disease olfactory mucosal cells obtained from live individuals secrete toxic amyloid-beta. We detail cell-type-specific gene expression patterns, unveiling 147 differentially expressed disease-associated genes compared to the cognitively healthy controls, and 5 distinct populations in globose basal cell -, myofibroblast-, and fibroblast/ stromal – like cellsin vitro. Overall, coordinated alteration of RNA and protein metabolism, inflammatory processes and signal transduction were observed in multiple cell populations, suggesting a key role in pathophysiology. Our results demonstrate the potential of olfactory cell cultures in modelling Alzheimer’s disease advocate their use for diagnostic purposes. Moreover, for the first time we provide single cell data on olfactory mucosa in Alzheimer’s disease for investigating molecular and cellular mechanisms associated with the disease.
Initial ciliary assembly inChlamydomonasrequires Arp2/3 complex-dependent endocytosis
Authors: Bigge Brae M , Rosenthal Nicholas E , Avasthi Prachee
Published: November 2020

Ciliary assembly, trafficking, and regulation are dependent on microtubules, but the mechanisms of ciliary assembly also require the actin cytoskeleton. Here, we dissect subcellular roles of actin in ciliogenesis by focusing on actin networks nucleated by the Arp2/3 complex in the powerful ciliary model,Chlamydomonas. We find the Arp2/3 complex is required for the initial stages of ciliary assembly when protein and membrane are in high demand but cannot yet be supplied from the Golgi complex. We provide evidence for Arp2/3 complex-dependent endocytosis of ciliary proteins, an increase in endocytic activity upon induction of ciliary growth, and relocalization of plasma membrane proteins to newly formed cilia. Our data support a new model of ciliary protein and membrane trafficking during early ciliogenesis whereby proteins previously targeted to the plasma membrane are reclaimed by Arp2/3 complex-dependent endocytosis for initial ciliary assembly.

Using the ciliary model systemChlamydomonas, we find Arp2/3 complex-mediated endocytosis is needed to reclaim cell body plasma membrane for early ciliary assembly.
Genomic evidence supports the introgression between two sympatric stickleback species inhabiting the White Sea basin
Authors: Nedoluzhko Artem , Sharko Fedor , Tsygankova Svetlana , Boulygina Eugenia , Ibragimova Amina , Teslyuk Anton , Galindo-Villegas Jorge , Rastorguev Sergey
Published: November 2020

Interspecies hybridization is driven by a complex interplay of factors where introgression plays an important role. In the present study, the transfer of genetic material, between two quite distant fish species from different genera, through spontaneous hybridization was documented with dedicated molecular and bioinformatics tools. We investigate the genomic landscape of putative stickleback-relative introgression by carefully analyzing the tractable transposable elements (TE) on the admixed genome of some individuals of two sympatric stickleback species inhabiting northwestern Russia, namely the three-spined (Gasterosteus aculeatus) and the nine-spined (Pungitius pungitius) sticklebacks. Our data revealed that unique TE amplification types exist, supporting our proposed hypothesis that infers on the interspecific introgression. By running a restriction site-associated DNA sequencing (RAD-Seq) with eight samples ofG. aculeatusandP. pungitiusand subjecting further the results to a contrasting analysis by variated bioinformatic tools, we identified the related introgression-linked markers. The admixture nature observed in a single sample of the nine-spined stickleback demonstrated the possible traces of remote introgression between these two species. Our work reveals the potential that introgression has on providing particular variants at a high-frequency speed while linking blocks of sequence with multiple functional mutations. However, even though our results are of significant interest, an increased number of samples displaying the introgression are required to further ascertain our conclusions.
QuantifyPolarity, a new tool-kit for measuring planar polarized protein distributions and cell properties in developing tissues
Authors: Tan Su Ee , Tan Weijie , Fisher Katherine H. , Strutt David
Published: November 2020

The coordination of cells or structures within the plane of a tissue is known as planar polarization. It is often governed by the asymmetric distribution of planar polarity proteins within cells. A number of quantitative methods have been developed to provide a readout of planar polarization of protein distributions. However, the quantification of planar polarization can be affected by different cell geometries. Hence, we developed a novel planar polarity quantification method based on Principal Component Analysis (PCA) that is shape insensitive. Here, we compare this method with other state-of-the-art methods on simulated models and biological datasets. We found that the PCA method performs robustly in quantifying planar polarity independently of variation in cell geometry. Furthermore, we designed a user-friendly graphical user interface called QuantifyPolarity, equipped with three different methods for automated quantification of polarity. QuantifyPolarity also provides image analysis tools to quantify cell morphology and packing geometry, allowing the relationship of these characteristics to planar polarization to be investigated. This all-in-one tool enables experimentalists with no prior computational expertise to perform high-throughput cell polarity and shape analysis automatically and efficiently.
A Primeval Mechanism of Tolerance to Desiccation Based on Glycolic Acid Saves Neurons from Ischemia in Mammals by Reducing Intracellular Calcium-Mediated Excitotoxicity
Authors: Chovsepian Alexandra , Berchtold Daniel , Winek Katarzyna , Mamrak Uta , Álvarez Inés Ramirez , Dening Yanina , Golubczyk Dominika , Weitbrecht Luis , Dames Claudia , Aillery Marine , Fernandez-Sanz Celia , Gajewski Zdzislaw , Dieterich Marianne , Janowski Miroslaw , Falkai Peter , Walczak Piotr , Plesnila Nikolaus , Meisel Andreas , Pan-Montojo Francisco
Published: November 2020

Stroke is the second leading cause of death and disability worldwide. Current treatments, such as pharmacological thrombolysis or mechanical thrombectomy, re-open occluded arteries but do not protect against ischemia-induced damage that has already occurred before reperfusion or ischemia/reperfusion-induced neuronal damage. It has been shown that disrupting the conversion of glyoxal to glycolic acid (GA) results in a decreased tolerance to anhydrobiosis inC. elegans, dauer larva, while GA itself can rescue this phenotype. During the process of desiccation/rehydration, a metabolic stop/start similar to the one observed during ischemia/reperfusion occurs. In this study, we tested the protective effect of GA in different ischemia models, including commonly used stroke models in mice and swine. Our results show that GA, given during reperfusion, strongly protects against ischemic damage and improves the functional outcome. We provide evidence that GA exerts its effect by counteracting the glutamate-dependent increase in intracellular calcium during excitotoxicity. These results suggest that GA treatment has the potential to reduce the mortality and disability caused by stroke in patients.
Longitudinal white matter changes associated with cognitive training
Authors: Nichols E.S. , Erez J. , Stojanoski B. , Lyons K.M. , Witt S.T. , Mace C.A. , Khalid S. , Owen A.M.
Published: November 2020

Improvements in behaviour are known to be accompanied by both structural and functional changes in the brain. However whether those changes lead to more general improvements, beyond the behaviour being trained, remains a contentious issue. We investigated whether training on one of two cognitive tasks would lead to either near transfer (that is, improvements on a quantifiably similar task) or far transfer (that is, improvements on a quantifiably different task), and furthermore, if such changes did occur, what the underlying neural mechanisms might be. Participants trained on either a verbal inhibitory control task or a visuospatial working memory task for four weeks, over the course of which they received five diffusion tensor imaging scans. Two additional tasks, a test of verbal reasoning and a test of spatial span, served as measures of near transfer for the inhibitory control task and spatial working memory task, respectively. These two tasks also served as measures of far transfer for the alternate training task. Behaviourally, participants improved on the task that they trained on, but did not improve on cognitively similar tests (near transfer), nor cognitively dissimilar tests (far transfer). Extensive changes to white matter microstructure were observed, with verbal inhibitory control training leading to changes in a left-lateralized network of fronto-temporal and occipito-frontal tracts, and visuospatial working memory training leading to changes in right-lateralized fronto-parietal tracts. Very little overlap was observed in changes between the two training groups. On the basis of these results, we suggest that near and far transfer were not observed because the changes in white matter tracts associated with training on each task are almost entirely non-overlapping with, and therefore afford no advantages for, the untrained tasks.
Heterochiasmy facilitated the establishment ofgsdfas a novel sex determining gene in Atlantic halibut
Authors: Edvardsen R.B. , Wallerman O. , Furmanek T. , Kleppe L. , Jern P. , Wallberg A. , Kjærner-Semb E. , Mæhle S. , Olausson S. K. , Sundström E. , Harboe T. , Mangor-Jensen R. , Møgster M. , Perrichon P. , Norberg B. , Rubin C-J
Published: November 2020

Atlantic Halibut (Hippoglossus hippoglossus) has a X/Y genetic sex determination system, but the sex determining factor is not known. We produced a high-quality genome assembly and identified parts of chromosome 13 as the Y chromosome due to sequence divergence between sexes and segregation of sex genotypes in pedigrees. Linkage analysis revealed that all chromosomes exhibit heterochiasmy, i.e. male- and female restricted meiotic recombination intervals (MRR/FRR). We show that FRR/MRR intervals differ in nucleotide diversity and repeat class content and that this is true also for other Pleuronectidae species. We further show that remnants of a Gypsy-like transposable element insertion on chr13 promotes early male specific expression of gonadal somatic cell derived factor (gsdf). Less than 4 MYA, this male-determining element evolved on an autosomal FRR segment featuring pre-existing male meiotic recombination barriers, thereby creating a Y chromosome. We propose that heterochiasmy may facilitate the evolution of genetic sex determination systems.
Increased Colonic Expression of ACE2 Associates with Poor Prognosis in Crohn’s disease
Authors: Toyonaga Takahiko , Araba Kenza C. , Kennedy Meaghan M. , Keith Benjamin P. , Wolber Elisabeth A. , Beasley Caroline , Steinbach Erin C. , Schaner Matthew R. , Jain Animesh , Long Millie D. , Barnes Edward L. , Herfarth Hans H. , Isaacs Kim L. , Hansen Jonathan J. , Kapadia Muneera , Gaston Guillem José , Koruda Mark J. , Rahbar Reza , Sadiq Tim , Gulati Ajay S. , Sethupathy Praveen , Furey Terrence S. , Ehre Camille , Sheikh Shehzad Z.
Published: November 2020

Background and Aims

The host receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small intestine. Our aim was to study colonic ACE2 expression in Crohn’s disease (CD) and non-inflammatory bowel disease (non-IBD) controls. We hypothesized that the colonic expression levels of ACE2 impacts CD course.

Methods

We examined the expression of colonACE2using RNA-seq and quantitative (q) RT-PCR from 69 adult CD and 14 NIBD control patients. In a subset of this cohort we validated ACE2 protein expression and localization in formalin-fixed, paraffin-embedded matched colon and ileal tissues using immunohistochemistry. The impact of increasedACE2expression in CD for the risk of surgery was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. To provide critical support for the generality of our findings, we analyzed previously published RNA-seq data from two large independent cohorts of CD patients.

Results

ColonicACE2expression was significantly higher in a subset of adult CD patients (ACE2-high CD). IHC in a sampling of ACE2-high CD patients confirmed high ACE2 protein expression in the colon and ileum compared to ACE2-low CD and NIBD patients. Notably, we found that ACE2-high CD patients are significantly more likely to undergo surgery within 5 years of diagnosis, with a Cox regression analysis finding that highACE2levels is an independent risk factor (OR 2.18; 95%CI, 1.05-4.55; p=0.037).

Conclusion

Increased intestinal expression of ACE2 is associated with deteriorated clinical outcomes in CD patients. These data point to the need for molecular stratification that may impact CD disease-related outcomes.
SUN-MKL1 crosstalk regulates nuclear deformation and fast motility of breast carcinoma cells in fibrillar ECM micro-environment
Authors: Sharma Ved P , Williams James , Leung Edison , Sanders Joe , Eddy Robert , Castracane James , Oktay Maja H , Entenberg David , Condeelis John S
Published: November 2020

Aligned collagen fibers provide topography for the rapid migration of single tumor cells (streaming migration) to invade the surrounding stroma, move within tumor nests towards blood vessels to intravasate and form distant metastases. Mechanisms of tumor cell motility have been studied extensively in the 2D context, but the mechanistic understanding of rapid single tumor cell motility in thein vivocontext is still lacking. Here, we show that streaming tumor cellsin vivouse collagen fibers with diameters below 3 μm. Employing 1D migration assays with matchingin vivofiber dimensions, we found a dependence of tumor cell motility on 1D substrate width, with cells moving the fastest and the most persistently on the narrowest 1D fibers (700 nm – 2.5 μm). Interestingly, we also observed nuclear deformation in the absence of restricting extracellular matrix pores during high speed carcinoma cell migration in 1D, similar to the nuclear deformation observed in tumor cellsin vivo. Further, we found that actomyosin machinery is aligned along the 1D axis and actomyosin contractility synchronously regulates cell motility and nuclear deformation. To further investigate the link between cell speed and nuclear deformation, we focused on the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex proteins and SRF-MKL1 signaling, key regulators of mechanotransduction, actomyosin contractility and actin-based cell motility. Analysis of The Cancer Genome Atlas dataset showed a dramatic decrease in the LINC complex proteins SUN1 and SUN2 in primary tumor compared to the normal tissue. Disruption of LINC complex by SUN1+2 KD led to multi-lobular elongated nuclei, increased tumor cell motility and concomitant increase in F-actin, without affecting Lamin proteins. Mechanistically, we found that MKL1, an effector of changes in cellular G-actin to F-actin ratio, is required for increased 1D motility seen in SUN1+2 KD cells. Thus, we demonstrate a previously unrecognized crosstalk between SUN proteins and MKL1 transcription factor in modulating nuclear shape and carcinoma cell motility in anin vivorelevant 1D microenvironment.
Time-resolved structured illumination microscopy reveals key principles of Xist RNA spreading
Authors: Rodermund Lisa , Coker Heather , Oldenkamp Roel , Wei Guifeng , Bowness Joseph , Rajkumar Bramman , Nesterova Tatyana , Pinto David , Schermelleh Lothar , Brockdorff Neil
Published: November 2020

Xist RNA directs the process of X-chromosome inactivation in mammals by spreadingin cisalong the chromosome from which it is transcribed and recruiting chromatin modifiers to silence gene transcription. To elucidate mechanisms of Xist RNAcis-confinement, we established a sequential dual color labeling, super-resolution imaging approach to trace individual Xist RNA molecules over time, enabling us to define fundamental parameters of spreading. We demonstrate a feedback mechanism linking Xist RNA synthesis and degradation, and an unexpected physical coupling between preceding and newly synthesized Xist RNA molecules. Additionally, we show that the protein SPEN, a key factor for Xist-mediated gene-silencing, has a distinct function in Xist RNA localization, stability and in coupling behavior. Our results provide important insights towards understanding the unique dynamic properties of Xist RNA.

One Sentence Summary

Visualizing Xist RNA dynamics in single cells during X chromosome inactivation
Crystal structure of chloroplastic thioredoxin z defines a novel type-specific target recognition
Authors: Le Moigne Théo , Gurrieri Libero , Crozet Pierre , Marchand Christophe H. , Zaffagnini Mirko , Sparla Francesca , Lemaire Stéphane D. , Henri Julien
Published: November 2020

Thioredoxins (TRXs) are ubiquitous disulfide oxidoreductases structured according to a highly conserved fold. TRXs are involved in a myriad of different processes through a common chemical mechanism. Plant thioredoxins evolved into seven types with diverse subcellular localization and distinct protein targets selectivity. Five TRX types coexist in the chloroplast, with yet scarcely described specificities. We solved the first crystal structure of a chloroplastic z-type TRX, revealing a conserved TRX fold with an original electrostatic surface potential surrounding the redox site. This recognition surface is distinct from all other known TRX types from plant and non-plant sources and is exclusively conserved in plant z-type TRXs. We show that this electronegative surface endows TRXz with a capacity to activate the photosynthetic Calvin-Benson cycle enzyme phosphoribulokinase. TRXz distinct electronegative surface thereby extends the repertoire of TRX-target recognitions.
Ovarian carcinosarcoma genomics and pre-clinical models highlight the N-MYC pathway as a key driver and susceptibility to EMT-targeting therapy
Authors: Ho Gwo Yaw , Kyran Elizabeth L. , Bedo Justin , Wakefield Matthew J. , Ennis Darren P. , Mirza Hasan B. , Lieschke Elizabeth , Vandenberg Cassandra J. , Kondrashova Olga , Upstill-Goddard Rosie , Bailey Ulla-Maja , Dowson Suzanne. , Roxburgh Patricia , Glasspool Rosalind M. , Bryson Gareth , Biankin Andrew V. , Cooke Susanna L. , Ratnayake Gayanie , McNally Orla , Traficante Nadia ,   Australian Ovarian Cancer Study, DeFazio Anna , Weroha John , Bowtell David D. , McNeish Iain A. , Papenfuss Anthony T. , Scott Clare L. , Barker Holly E.
Published: November 2020

Ovarian carcinosarcoma (OCS) is an aggressive and rare tumour type with limited treatment options. OCS is hypothesised to develop via the combination theory from a single progenitor, resulting in carcinomatous and sarcomatous components, or alternatively via the conversion theory, with the sarcomatous component developing from the carcinomatous component through epithelial-to-mesenchymal transition (EMT). We show OCS from 18 women to be monoclonal through analysis of DNA variants from isolated carcinoma and sarcoma components. RNA sequencing indicated the carcinoma components were more mesenchymal when compared with pure ovarian carcinomas, supporting the conversion theory. We used pre-clinical OCS models to test the efficacy of microtubule-targeting drugs, including eribulin, which has been shown to reverse EMT characteristics. We demonstrated that microtubule inhibitors, vinorelbine and eribulin, were more effective than standard-of-care platinum-based chemotherapy. Eribulin reduced mesenchymal characteristics, N-MYC expression and cholesterol biosynthesis. Finally, eribulin induced a strong immune response, supporting immunotherapy combinations in the clinic.
The structural connectome constrains fast brain dynamics
Authors: Sorrentino P , Seguin C , Rucco R , Liparoti M , Troisi Lopez E , Bonavita S , Quarantelli M , Sorrentino G , Jirsa V , Zalesky A
Published: November 2020

Brain activity during rest displays complex, rapidly evolving patterns in space and time. Structural connections comprising the human connectome are hypothesized to impose constraints on the dynamics of this activity. Here, we use magnetoencephalography (MEG) to quantify the extent to which fast neural dynamics in the human brain are constrained by structural connections inferred from diffusion MRI tractography. We characterize the spatio-temporal unfolding of whole-brain activity at the millisecond scale from source-reconstructed MEG data, estimating the probability that any two brain regions will significantly deviate from baseline activity in consecutive time epochs. We find that the structural connectome relates to, and likely affects, the rapid spreading of neuronal avalanches, evidenced by a significant association between these transition probabilities and structural connectivity strengths (r=0.37, p<0.0001). This finding opens new avenues to study the relationship between brain structure and neural dynamics.
An Ultra-Stable and Dense Single-Molecule Click Platform for Sensing Protein-DNA Interactions
Authors: Visser Emiel W. A. , Miladinovic Jovana , Milstein Joshua N.
Published: November 2020

We demonstrate an ultra-stable, highly dense single-molecule assay ideal for observing protein-DNA interactions. Stable click Tethered Particle Motion (scTPM) leverages next generation click-chemistry to achieve an ultrahigh density of surface tethered reporter particles, has a high antifouling resistance, is stable at elevated temperatures to at least 45 °C, and is compatible with Mg2+, an important ionic component of many regulatory protein-DNA interactions. Prepared samples remain stable, with little degradation, for > 6 months in physiological buffers. These improvements enabled us to study previously inaccessible sequence and temperature dependent effects on DNA binding by the bacterial protein H-NS, a global transcriptional regulator found in E. Coli. This greatly improved assay can directly be translated to accelerate existing tethered particle based, single-molecule biosensing applications.
Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms
Authors: Malik Asad U. , Karapetsas Athanasios , Nirujogi Raja S. , Mathea Sebastian , Pal Prosenjit , Lis Pawel , Taylor Matthew , Purlyte Elena , Gourlay Robert , Dorward Mark , Weidlich Simone , Toth Rachel , Polinski Nicole K. , Knapp Stefan , Tonelli Francesca , Alessi Dario R
Published: November 2020

Much attention has focused on LRRK2, as autosomal dominant missense mutations that enhance its kinase activity cause inherited Parkinson’s disease. LRRK2 regulates biology by phosphorylating a subset of Rab GTPases including Rab8A and Rab10 within its effector binding motif. In this study we explore whether LRRK1, a less studied homologue of LRRK2 that regulates growth factor receptor trafficking and osteoclast biology might also phosphorylate Rab proteins. Using mass spectrometry, we found that the endogenous Rab7A protein, phosphorylated at Ser72 was most impacted by LRRK1 knock-out. This residue is not phosphorylated by LRRK2 but lies at the equivalent site targeted by LRRK2 on Rab8A and Rab10. Accordingly, recombinant LRRK1 efficiently phosphorylated Rab7A at Ser72, but not Rab8A or Rab10. Employing a novel phospho-specific antibody, we found that phorbol ester stimulation of mouse embryonic fibroblasts markedly enhanced phosphorylation of Rab7A at Ser72 via LRRK1. We identify two LRRK1 mutations (K746G and I1412T), equivalent to the LRRK2 R1441G and I2020T Parkinson’s mutations, that enhance LRRK1 mediated phosphorylation of Rab7A. We demonstrate that two regulators of LRRK2 namely Rab29 and VPS35[D620N], do not influence LRRK1. Widely used LRRK2 inhibitors do not inhibit LRRK1, but we identify a promiscuous Type-2 tyrosine kinase inhibitor termed GZD-824 that inhibits both LRRK1 and LRRK2. Finally, we show that interaction of Rab7A with its effector RILP is not affected by high stoichiometry LRRK1 phosphorylation. Altogether, these finding reinforce the idea that the LRRK enzymes have evolved as major regulators of Rab biology.
Synergistic CDK control pathways maintain cell size homeostasis
Authors: Patterson James O. , Basu Souradeep , Rees Paul , Nurse Paul
Published: November 2020

To coordinate cell size with cell division, cell size must be computed by the cyclin-CDK control network to trigger division appropriately. Here we dissect determinants of cyclin-CDK activity using a novel high-throughput single-cell in vivo system. We show that inhibitory phosphorylation of CDK encodes cell size information and works synergistically with PP2A to prevent division in smaller cells. However, even in the absence of all canonical regulators of cyclin-CDK, small cells with high cyclin-CDK levels are restricted from dividing. We find that diploid cells of equivalent size to haploid cells exhibit lower CDK activity in response to equal cyclin-CDK enzyme concentrations, suggesting that CDK activity is reduced by DNA concentration. Thus, multiple pathways directly regulate cyclin-CDK activity to maintain robust cell size homeostasis.
Distortions, deviations and alternative facts: reliability in crystallography
Authors: Clegg William
Published: November 2020

This feature article is derived from the author's presentation of the Lonsdale lecture at the BCA Spring Meeting in 2018. One of the research results for which Kathleen Lonsdale is best known was her 1929 demonstration that the benzene ring in crystalline hexamethylbenzene is planar and has essentially hexagonal symmetry, resolving decades of dispute among organic chemists. More recent crystallographic studies of hexamethylbenzene have shown that there are actually small deviations from planarity. Such deviations for aromatic compounds may be due to electronic, steric, and/or intermolecular factors. Some substituted benzene molecules display remarkably large deviations, both from a planar ring structure and from regular hexagonal angular geometry around the ring. Starting from this specific connection with Kathleen Lonsdale's research, a number of stories are recounted of structural distortions and deviations from expected results and explanations that have been suggested for them, across a wide range of chemical topics including macrocycles, metal clusters, unusual coordination geometry and isomerism. On the way we find genuine surprises and results that have led to new understanding, but also examples of poor experiments, misinterpretation of data, scientific bias and preconceived ideas, incompetence and even deliberate fraud. Some aspects of structure validation are discussed. While showcasing some interesting research in its own right, this account also serves an educational purpose.
Effect of volatility of foreign direct investment inflows on corporate income tax revenue volatility
Authors: Gnangnon Sena Kimm
Published: November 2020

Purpose

This paper aims to examine how the volatility of foreign direct investment (FDI) inflows affects the volatility of corporate income tax revenue.

Design/methodology/approach

The study has used an unbalanced panel data set of 129 countries over the period 1981–2016 and the two-step system generalized methods of moment approach to perform the empirical analysis.

Findings

The main findings are that FDI volatility enhances the volatility of corporate income tax revenue in less advanced economies, but reduces it in relatively advanced countries. The positive corporate income tax revenue volatility effect of FDI inflows is far higher in non-tax haven countries than in tax haven countries. Additionally, FDI volatility exerts a higher positive effect on corporate income tax revenue volatility as countries experience greater dependence on natural resources. Finally, the positive effect of FDI volatility on corporate income tax revenue volatility is further amplified by higher FDI volatility.

Research limitations/implications

One important limitation of the present analysis is the use of aggregate FDI inflows because of the lack of data over a long period on greenfield FDI inflows and cross-border mergers and acquisitions FDI inflows. Therefore, an avenue for future research could be to explore separately the effect of the volatility greenfield FDI inflows and the volatility of cross-border mergers and acquisitions FDI inflows on the volatility of corporate income tax revenue, when long-time series data (covering many countries) would be available.

Practical implications

These outcomes particularly shed light on the role of FDI volatility on the volatility of corporate income tax revenue, particularly in countries that are highly dependent on natural resources. Foreign capital flows, notably FDI flows, play an essential role for countries’ economic development through, inter alia, technology transfer, jobs creation and economic growth. Policymakers should aim to attract FDI, while also reducing their volatility, by designing and implementing policies and measures (such as those in favor of business environment improvement, property rights enforcement and political stability) that would assure foreign investors of the continuous high returns of their investments.

Originality/value

To the best of the author’s knowledge, this is the first time this topic is being addressed empirically in the literature.
Spam detection and high-quality features to analyse question –answer pairs
Authors: Wang Hei Chia , Chiang Yu Hung , Lin Si Ting
Published: November 2020

Purpose

In community question and answer (CQA) services, because of user subjectivity and the limits of knowledge, the distribution of answer quality can vary drastically – from highly related to irrelevant or even spam answers. Previous studies of CQA portals have faced two important issues: answer quality analysis and spam answer filtering. Therefore, the purposes of this study are to filter spam answers in advance using two-phase identification methods and then automatically classify the different types of question and answer (QA) pairs by deep learning. Finally, this study proposes a comprehensive study of answer quality prediction for different types of QA pairs.

Design/methodology/approach

This study proposes an integrated model with a two-phase identification method that filters spam answers in advance and uses a deep learning method [recurrent convolutional neural network (R-CNN)] to automatically classify various types of questions. Logistic regression (LR) is further applied to examine which answer quality features significantly indicate high-quality answers to different types of questions.

Findings

There are four prominent findings. (1) This study confirms that conducting spam filtering before an answer quality analysis can reduce the proportion of high-quality answers that are misjudged as spam answers. (2) The experimental results show that answer quality is better when question types are included. (3) The analysis results for different classifiers show that the R-CNN achieves the best macro-F1 scores (74.8%) in the question type classification module. (4) Finally, the experimental results by LR show that author ranking, answer length and common words could significantly impact answer quality for different types of questions.

Originality/value

The proposed system is simultaneously able to detect spam answers and provide users with quick and efficient retrieval mechanisms for high-quality answers to different types of questions in CQA. Moreover, this study further validates that crucial features exist among the different types of questions that can impact answer quality. Overall, an identification system automatically summarises high-quality answers for each different type of questions from the pool of messy answers in CQA, which can be very useful in helping users make decisions.
Can “bad” stressors spark “good” behaviors in frontline employees? Incorporating motivation and emotion
Authors: Wang Jiaxin (Sylvia) , Fu Xiaoxiao , Wang Youcheng
Published: November 2020

Purpose

This study aims to investigate the antecedents of frontline employees’ boundary-spanning behaviors in the hospitality industry. Anchored in transactional stress theory, affective events theory and motivation theories, a conceptual model was built to explore the impacts of hindrance stressors on boundary-spanning behavior.

Design/methodology/approach

Data were collected from frontline employees in the hospitality industry in the USA. Confirmatory factor analysis and structural equation modeling were used.

Findings

The findings revealed that despite hindrance stressors’ negative indirect impact on frontline employees’ boundary-spanning behaviors, intrinsic motivation worked effectively to reduce hindrance stress and influence subsequent emotions leading to boundary-spanning behaviors.

Practical implications

This study provides substantial and detailed strategies for hospitality practitioners who are pressed to alleviate the hindrance stressors from which frontline employees frequently suffer, foster employees’ positive emotions and ease negative emotions while promoting boundary-spanning behaviors. Cultivation of employees’ intrinsic motivation and emotional management is encouraged, as is effective organizational structure and management intervention. All of these are deemed helpful in buffering employees’ work-related stress while motivating them to go above and beyond their nominal duties.

Originality/value

Very few studies have examined how “bad” hindrance stressors affect boundary-spanning behaviors. Rather than suggesting that hindrance stressors are relevant only to counterproductive behaviors, this study extends both the stress and boundary-spanning literature by uncovering the impact of hindrance stressors on frontline employees’ boundary-spanning behaviors while accounting for the roles of workers’ motivation and emotion.
Application of consumer innovativeness to the context of robotic restaurants
Authors: Kim Jinkyung Jenny , Choe Ja Young (Jacey) , Hwang Jinsoo
Published: November 2020

Purpose

The purpose of this paper is to apply the concept of consumer innovativeness to the robotic restaurants field.

Design/methodology/approach

A research model including 13 hypotheses is examined using a sample of 409 subjects gathered.

Findings

The results indicate that four underlying dimensions of consumer innovativeness have a positive effect on overall image, which, in turn, increases desire. In addition, desire aids to enhance the two dimensions of behavior intentions.

Practical implications

Robotic restaurant managers are required to focus more on quality experience-seeking, hedonic experience-seeking, venturesomeness and social distinctiveness using automated systems, which aid to enhance the image of robotic restaurants.

Originality/value

Consumer innovativeness is regarded as a significant concept in the domain of a novel technology-based product and service, but it has not been explored in the restaurant context. Thus, this study tried to apply consumer innovativeness to the robotic restaurant industry for the first time and explained how to form consumer behavioral intentions based on the concept.
Identifying interrelationships among factors affecting innovation archetypes: the case of China
Authors: Al-Sayed Rafif , Yang Jianhua
Published: November 2020

Purpose

This paper aims at studying the concept of innovation ecosystems and investigating the factors affecting them based on their interrelationships with respect to different innovation archetypes.

Design/methodology/approach

The methodology is based on using multivariate statistical analysis of the inter-correlations among a number of variables which led to extracting a reduced set of new significant factors that affect China’s innovation ecosystem.

Findings

The results showed that innovation archetypes differ significantly with respect to the majority of the new factors.

Practical implications

Through identifying these challenges, decision-makers can develop a better understanding of the variables affecting each archetype of innovation and act accordingly.

Originality/value

The study is the first to fill the gap of addressing a large number of variables affecting innovation and analyzing their interrelationships.
An RSSI-based Sybil attack detection system with continuous authentication using a novel lightweight multimodal biometrics
Authors: Brindha N.V. , Meenakshi V.S.
Published: November 2020

Purpose

Any node in a mobile ad hoc network (MANET) can act as a host or router at any time and so, the nodes in the MANET are vulnerable to many types of attacks. Sybil attack is one of the harmful attacks in the MANET, which produces fake identities similar to legitimate nodes in the network. It is a serious threat to the MANET when a malicious node uses the fake identities to enter the network illegally.

Design/methodology/approach

A MANET is an independent collection of mobile nodes that form a temporary or arbitrary network without any fixed infrastructure. The nodes in the MANET lack centralized administration to manage the network and change their links to other devices frequently.

Findings

So for securing a MANET, an approach based on biometric authentication can be used. The multimodal biometric technology has been providing some more potential solutions for the user to be able to devise an authentication in MANETs of high security.

Research limitations/implications

The Sybil detection approach, which is based on the received signal strength indicator (RSSI) variations, permits the node to be able to verify the authenticity of communicating nodes in accordance with their localizations.

Practical implications

As the MANET node suffers from a low level of memory and power of computation, there is a novel technique of feature extraction that is proposed for the multimodal biometrics that makes use of palm prints that are based on a charge-coupled device and fingerprints, along with the features that are fused.

Social implications

This paper proposes an RSSI-based multimodal biometric solution to detect Sybil attack in MANETs.

Originality/value

The results of the experiment have indicated that this method has achieved a performance which is better compared to that of the other methods.
Value creation through innovation in the primary sector
Authors: Colman Pablo , Harwell Jan , Found Pauline
Published: November 2020

Purpose

Innovation is a growing topic. The primary sector is also a subject that has great importance in the global economy. However, limited research has been conducted linking these two subjects. This paper aims to start bringing them together.

Design/methodology/approach

The method selected is a systematic literature review presenting a thorough analysis of the existing discussions and a summary of the findings to identify future research opportunities.

Findings

Innovation has played and will continue to play an essential role in the success of fisheries. The fishing industry is in crisis. A decline in wild fish stocks, regulations and quota management are some of the factors that drive the need to innovate. The discussions of innovation in this industry are non-technological, which is an emerging field with opportunities for further research. There is a strong focus on fisheries sustainability. The main theoretical frameworks discussed in the literature are common property theory, cooperation and competition theory and diffusion of innovation. Emerging environmental sustainability frameworks are also becoming an essential element in the primary sector.

Research limitations/implications

This paper focuses on peer-reviewed publications based on the results of the searches from selected keywords, recognizing that the literature evaluated may not cover the full spectrum of themes related to this subject.

Originality/value

Innovation is usually linked to high tech and fast-moving industries. This paper tries to broaden this paradigm and evaluate it from a different perspective, with a focus on the primary sector.
Inquiry in higher education for sustainable development: crossing disciplinary knowledge boundaries
Authors: Galvão Cecília , Faria Cláudia , Viegas Wanda , Branco Amélia , Goulão Luís
Published: November 2020

Purpose

This paper aims to understand if a project work methodology proposed to students, based on an inquiry perspective and dealing with different dimensions of sustainable development, contributed to creating an interdisciplinary solution for a problem on sustainability challenged by food production and consumption, and also to understand if this methodological approach is perceived as important to their learning as professionals and citizens. Data were collected by direct observation, a questionnaire applied to the students and students’ individual reflections.

Design/methodology/approach

This paper aims to present the research results of the impact of a pedagogical approach on students, implemented as a part of the Doctoral Programme in Sustainability Science, which was designed following an innovative model at the University of Lisbon, Portugal. The main drivers include building a new body of interdisciplinary knowledge leading to the application of science to address real problems towards transdisciplinary education.

Findings

The results suggest great potential for an inquiry perspective in trying to solve a real problem. Students’ proposals were realistic, viable and complementary enough to collectively contribute in response to the global problem. The use of approaches acquired from different areas of knowledge was clear, and the project methodology was well understood. Students considered the experience very rewarding in terms of learning and contributing positively to their personal and professional development.

Originality/value

This Doctoral programme is anchored in a progressive continuum encompassing holistic debates with a multidisciplinary team of professors in environments that promote interdisciplinary attitudes and new knowledge, and also project work aimed at guiding students to transdisciplinary learning, which constitutes an innovative form of dealing with the complex challenges created by the science of sustainability.
A review of challenges and opportunities of blockchain adoption for operational excellence in the UK automotive industry
Authors: Upadhyay Arvind , Ayodele Julius Oluwasunkanmi , Kumar Anil , Garza-Reyes Jose Arturo
Published: November 2020

Purpose

This paper aims to explore the challenges and opportunities of blockchain technology adoption from the lens of the technological–organisational–environmental (TOE) framework for operational excellence in the UK automotive industry context.

Design/methodology/approach

The research methodology of this study follows a systematic review approach, which analyses existing academic published research papers in the top 35 academic journals. There was no specific timeframe established for this study and shortlisting the articles through a set of used keywords. A sample of 71 articles was shortlisted and analysed to provide a discussion on technological and management challenges and opportunities of blockchain adoption from the lens of the TOE framework for operational excellence.

Findings

The findings of this study present significant theoretical and managerial implications and deep understanding for firms seeking to understand the challenges and opportunities of blockchain adoption for their operational excellence.

Research limitations/implications

The systematic literature approach was considered for the present study to explore existing academic papers on technological and management challenges and opportunities from the lens of TOE framework for operational excellence, whereas a more specified method meta-analysis can be considered for future research. The study has been explored in the UK automotive industry context, which has been considered as the limitation of generalisation across countries and industries.

Originality/value

This paper represents the most comprehensive literature study related to the technological and management challenges and opportunities of blockchain from the TOE framework angle for operational excellence.