bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence of genetic overlap between circadian preference and brain white matter microstructure
Authors: García-Marín Luis M. , Alcauter Sarael , Campos Adrian I. , Mulcahy Aoibhe , Kho Pik-Fang , Cuéllar-Partida Gabriel , Rentería Miguel E.
Published: November 2020

Study objective

Previous neuroimaging studies have highlighted differences in white matter microstructure among individuals with different chronotypes, but it is unclear whether those differences are due to genetic or environmental factors.

Methods

Here we leverage summary statistics from recent large-scale genome-wide association studies (GWAS) of chronotype and diffusion tensor imaging (DTI) measures to examine the genetic overlap and infer causal relationships between these traits.

Results

We identified 29 significant pairwise genetic correlations, of which 13 also had evidence for a causal association. Negative genetic correlations were identified between chronotype and brain-wide mean, axial and radial diffusivities. When exploring individual tracts, ten negative genetic correlations were observed with mean diffusivities, 10 with axial diffusivities, 4 with radial diffusivities and 2 with mode of anisotropy. We found evidence for a possible causal association of chronotype with white matter microstructure in individual tracts including the posterior limb and retrolenticular part of the internal capsule; the genu and splenium of the corpus callosum and the posterior, superior and anterior regions of the corona radiata.

Conclusions

Our results suggest thateveningnessis associated with variation in tract-specific white matter microstructure and, for an evening person, increases in axial and / or radial diffusivities may influence a higher mean diffusivity. These findings add to our understanding of circadian preference and its relationship with the brain, providing new perspectives on the genetic neurological underpinnings of chronotype’s role in health and disease.

Statement of Significance

Sleep is essential for a healthy brain function, particularly for neural organization and brain structure development. Individual chronotype differences have been associated with depression, schizophrenia, diabetes and obesity, among other conditions. Investigating the shared genetic aetiology between chronotype and white matter microstructure is essential to understand the neurological basis of individual variation in chronotype. In the present study, we show that tract-specific white matter microstructure is genetically correlated and causally associated with chronotype.
Single cell transcriptomic re-analysis of immune cells in bronchoalveolar lavage fluids reveals the correlation of B cell characteristics and disease severity of patients with SARS-CoV-2 infection
Authors: Kim Chae Won , Oh Ji Eun , Lee Heung Kyu
Published: November 2020

The COVID-19 pandemic (SARS-CoV-2) is a global infectious disease with rapid spread. Some patients have severe symptoms and clinical signs caused by an excessive inflammatory response, which increases the risk of mortality. In this study, we reanalyzed scRNA-seq data of cells from bronchoalveolar lavage fluids of patients with COVID-19 with mild and severe symptoms, focusing on antibody-producing cells. In patients with severe disease, B cells seemed to be more activated and expressed more immunoglobulin genes compared with cells from patients with mild disease, and macrophages expressed higher levels of the TNF superfamily member B-cell activating factor but not of APRIL (a proliferation-inducing ligand). In addition, macrophages from patients with severe disease had increased pro-inflammatory features and pathways associated with Fc receptor-mediated signaling, compared with patients with mild disease. CCR2-positive plasma cells accumulated in patients with severe disease, probably because of increased CCL2 expression on macrophages from patients with severe disease. Together, these results support that different characteristics of B cells might affect the severity of COVID-19 infection.
Modelling the impact of the macroalgaeAsparagopsis taxiformison rumen microbial fermentation and methane production
Authors: Muñoz-Tamayo Rafael , Chagas Juana C. , Ramin Mohammad , Krizsan Sophie J.
Published: November 2020

Abstract

Background

The red macroalgae Asparagopsis taxiformis is a potent natural supplement for reducing methane production from cattle. A. taxiformis contains several anti-methanogenic compounds including bromoform that inhibits directly methanogenesis. The positive and adverse effects of A. taxiformis on the rumen microbiota are dose-dependent and operate in a dynamic fashion. It is therefore key to characterize the dynamic response of the rumen microbial fermentation for identifying optimal conditions on the use of A. taxiformis as a dietary supplement for methane mitigation. Accordingly, the objective of this work was to model the effect of A. taxiformis supplementation on the rumen microbial fermentation under in vitro conditions. We adapted a published mathematical model of rumen microbial fermentation to account for A. taxiformis supplementation. We modelled the impact of A. taxiformis on the fermentation and methane production by two mechanisms, namely (i) direct inhibition of the growth rate of methanogens by bromoform and (ii) hydrogen control on sugars utilization and on the flux allocation towards volatile fatty acids production. We calibrated our model using a multi-experiment estimation approach that integrated experimental data with six macroalgae supplementation levels from a published in vitro study assessing the dose-response impact of A. taxiformis on rumen fermentation.

Results

our model captured satisfactorily the effect of A. taxiformis on the dynamic profile of rumen microbial fermentation for the six supplementation levels of A. taxiformis with an average determination coefficient of 0.88 and an average coefficient of variation of the root mean squared error of 15.2% for acetate, butyrate, propionate, ammonia and methane.

Conclusions

our results indicated the potential of our model as prediction tool for assessing the impact of additives such as seaweeds on the rumen microbial fermentation and methane production in vitro. Additional dynamic data on hydrogen and bromoform are required to validate our model structure and look for model structure improvements. We expect this model development can be useful to help the design of sustainable nutritional strategies promoting healthy rumen function and low environmental footprint.
A tractable bottom-up model of the yeast polarity genotype-phenotype map for evolutionary relevant predictions
Authors: Daalman Werner Karl-Gustav , Sweep Els , Laan Liedewij
Published: November 2020

Accurate phenotype prediction based on genetic information has numerous societal applications, such as crop design or cellular factories. Epistasis, when biological components interact, complicates modelling phenotypes from genotypes. Here we show an approach to mitigate this complication for polarity establishment in budding yeast, where mechanistic information is abundant. We coarse-grain molecular interactions into a so-called mesotype, which we combine with gene expression noise into a physical cell cycle model. Firstly, we show with computer simulations that the mesotype allows validation of the most current biochemical polarity models by quantitatively matching doubling times. Secondly, the mesotype elucidates epistasis emergence as exemplified by evaluating the predicted mutational effect of key polarity protein Bem1p when combined with known interactors or under different growth conditions. This example also illustrates how unlikely evolutionary trajectories can become more accessible. The tractability of our biophysically justifiable approach inspires a road-map towards bottom-up phenotype modelling beyond statistical inferences.
Small Animal Jet Injection Technique Results in Enhanced Immunogenicity of Hantavirus DNA Vaccines
Authors: Brocato Rebecca L. , Kwilas Steven A. , Josleyn Matthew D. , Long Simon , Zeng Xiankun , Perley Casey C. , Principe Lucia M. , Somerville Brandon , Cohen Melanie V. , Hooper Jay W.
Published: November 2020

DNA vaccine evaluation in small animals is hampered by low immunogenicity when the vaccines are delivered using a needle and syringe. To overcome this technical hurdle we tested the possibility that a device developed for human intradermal medicine delivery might be adapted to successfully deliver a DNA vaccine to small animals. The PharmaJet®Tropis device is a FDA 510(k)-cleared disposable syringe, needle-free jet injection device designed to administer medicines to the human dermis in a 0.1 mL volume. Here, we found that hantavirus DNA vaccines administered to Syrian hamsters using Tropis were substantially more immunogenic than the same vaccines delivered by needle/syringe or particle mediated epidermal delivery (gene gun) vaccination. By adjusting how the device was used we could deliver vaccine to either subcutaneous tissues, or through the skin into the muscle. RNA and/or antigen expression was detected in epidermal, subepidermal and fibroblast cells. We directly compared six optimized and non-optimized hantavirus DNA vaccines in hamsters. Optimization, including codon-usage and mRNA stability, did not necessarily result in increased immunogenicity for all vaccines tested; however, optimization of the Andes virus (ANDV) DNA vaccine protected vaccinated hamsters from lethal disease. This is the first time active vaccination with an ANDV DNA vaccine has shown protective efficacy in the hamster model. The adaptation of a human intradermal jet injection device for use as a method of subcutaneous and intramuscular jet injection of DNA vaccines will advance the development of nucleic acid based medical countermeasures for diseases modeled in hamsters.
Impact of the pear psyllidCacopsylla pyrihost instar on the behavior and fitness of the parasitoidTrechnites insidious
Authors: Le Goff Guillaume Jean , Berthe Jeremy , Tougeron Kévin , Dochy Benoit , Lebbe Olivier , Renoz François , Hance Thierry
Published: November 2020

Pear is one of the most important fruit crops of temperate regions. The control of its mains pest,Cacopsylla pyri, is still largely based on the use of chemical pesticides, with all that this implies in terms of negative effects on the environment and health.

Within the context of integrated pest management, innovative and ecologically sustainable strategies must be developed for. AlthoughTrechnites insidiosusis the most abundant parasitoid ofC. pyri, its biology and its potential as a control agent have been little studied.

In this paper, we conducted experiments to evaluate the behavior of the specialist parasitoidT. insidiosuswhen exposed to different larval instars of the pear psyllidC. pyri, and to assess the quality of the next generation of parasitoids.

We found that althoughT. insidiosusaccepts all host instars for oviposition, the third and fourth instars were the most suitable host in terms of behavioral acceptance and progeny development.

Our study is a first step for further studies on the interaction between psyllids and parasitoids and provides evidence that the specialist parasitoidT. insidiosusis a promising candidate for biological control strategies of the pear psyllidC. pyri.
Astrocytes drive divergent metabolic gene expression in humans and chimpanzees
Authors: Zintel Trisha M. , Pizzollo Jason , Claypool Christopher G. , Babbitt Courtney C.
Published: November 2020

The human brain utilizes ∼ 20% of all of the body’s metabolic resources, while chimpanzee brains use less than 10%. Although previous work shows significant differences in metabolic gene expression between the brains of primates, we have yet to fully resolve the contribution of distinct brain cell types. To investigate cell-type specific interspecies differences in brain gene expression, we conducted RNA-Seq on neural progenitor cells (NPCs), neurons, and astrocytes generated from induced pluripotent stem cells (iPSCs) from humans and chimpanzees. Interspecies differential expression (DE) analyses revealed that twice as many genes exhibit DE in astrocytes (12.2% of all genes expressed) than neurons (5.8%). Pathway enrichment analyses determined that astrocytes, rather than neurons, diverged in expression of glucose and lactate transmembrane transport, as well as pyruvate processing and oxidative phosphorylation. These findings suggest that astrocytes may have contributed significantly to the evolution of greater brain glucose metabolism with proximity to humans.
Sphingolipid changes in Parkinson L444P GBA mutation fibroblasts promote α-synuclein aggregation
Authors: Galvagnion Céline , Cerri Silvia , Schapira Anthony H.V. , Blandini Fabio , Di Monte Donato A.
Published: November 2020

Intraneuronal accumulation of aggregated α-synuclein is a pathological hallmark of Parkinson’s disease. Therefore, mechanisms capable of promoting α-synuclein deposition bear important pathogenetic implications. Mutations of the glucocerebrosidase 1 (GBA) gene represent a prevalent Parkinson’s disease risk factor. They are associated with loss of activity of a key enzyme involved in lipid metabolism, glucocerebrosidase, supporting a mechanistic relationship between abnormal α-synuclein-lipid interactions and the development of Parkinson pathology. In this study, the lipid membrane composition of fibroblasts isolated from control subjects, patients with idiopathic Parkinson’s disease (iPD) and Parkinson patients carrying the L444PGBAmutation (PD-GBA) was assayed using shotgun lipidomics. The lipid profile of PD-GBA fibroblasts differed significantly from that of control and iPD cells. It was characterized by an overall increase in sphingolipid levels. It also featured a significant change in the proportion of ceramide, sphingomyelin and hexosylceramide molecules with shorter and longer hydrocarbon chain length; levels of shorter-chain molecules were increased while the percent of longer-chain sphingolipids was decreased in PD-GBA lipid extracts. The extent of this shift was correlated to the degree of reduction of fibroblast glucocerebrosidase activity. In a second set of experiments, lipid extracts from control and PD-GBA fibroblasts were added to incubations of recombinant α-synuclein. The kinetics of α-synuclein aggregation, as assessed by the binding of thioflavin T to amyloid structures, was significantly accelerated after addition of PD-GBA extracts as compared to control samples. Amyloid fibrils collected at the end of these incubations contained lipids, indicating α-synuclein-lipid co-assembly. Lipids extracted from α-synuclein fibrils were also analysed by shotgun lipidomics. Data revealed that the lipid content of these fibrils was significantly enriched of shorter-chain sphingolipids. Taken together, findings of this study indicate that the L444PGBAmutation and consequent enzymatic loss are associated with a distinctly altered membrane lipid profile that provides a biological fingerprint of this mutation in Parkinson fibroblasts. This altered lipid profile, which includes an increased content of shorter-chain sphingolipids, could also be an indicator of increased risk for α-synuclein aggregate pathology. Shorter-chain molecules may act as preferred reactants during lipid-induced α-synuclein fibrillation.
Dilp8 controls a time window for tissue size adjustment inDrosophila
Authors: Boulan L. , Blanco-Obregon D. , El Marzkioui K. , Brutscher F. , Andersen D.S. , Colombani J. , Narasimha S. , Léopold P.
Published: November 2020

The control of organ size mainly relies on precise autonomous growth programs. However, organ development is subject to random variations, called developmental noise, best revealed by the fluctuating asymmetry observed between bilateral organs. The developmental mechanisms ensuring bilateral symmetry in organ size are mostly unknown. InDrosophila, null mutations for the relaxin-like hormone Dilp8 increase wing fluctuating asymmetry, suggesting that Dilp8 plays a role in buffering developmental noise. Here we show that size adjustment of the wing primordia involves a peak of Dilp8 expression that takes place sharply at the end of juvenile growth. Wing size adjustment relies on a crossorgan communication involving the epidermis as the source of Dilp8. We identify ecdysone signaling as both the trigger for epidermaldilp8expression and its downstream target in the wing primordia, thereby establishing reciprocal feedback between the two hormones as a systemic mechanism controlling organ size precision. Our results reveal a hormone-based time window ensuring fine-tuning of organ size and bilateral symmetry.
Gain-of-function assay for SARS-CoV-2 Mproinhibition in living cells
Authors: Moghadasi Seyad Arad , Becker Jordan T. , Belica Christopher , Wick Chloe , Brown William L. , Harris Reuben S.
Published: November 2020

The main protease, Mpro, of SARS-CoV-2 is required to cleave the viral polyprotein into precise functional units for virus replication and pathogenesis. Here we demonstrate a quantitative reporter for Mprofunction in living cells, in which protease inhibition by genetic or chemical methods results in strong eGFP fluorescence. This robust gain-of-function system readily distinguishes between inhibitor potencies and can be scaled-up to high-throughput platforms for drug testing.
Acute ethanol stress induces sumoylation of conserved chromatin structural proteins inSaccharomyces cerevisiae
Authors: Bradley Amanda I. , Marsh Nicole M. , Borror Heather R. , Mostoller Kaitlyn E. , Gama Amber I. , Gardner Richard G.
Published: November 2020

Stress is a ubiquitous part of life that disrupts cellular function and, if unresolved, can irreparably damage essential biomolecules and organelles. All organisms can experience stress in the form of unfavorable environmental conditions including exposure to extreme temperatures, hypoxia, reactive oxygen species, alcohol, or shifts in osmolarity. To survive, organisms must sense these changes then react and adapt. One highly conserved adaptive response to stress is through protein sumoylation, which is a post-translational modification by thesmallubiquitin-likemodifier (SUMO) protein. In this study, we examine the effects of acute ethanol stress on protein sumoylation in the budding yeastSaccharomyces cerevisiae. Although ethanol induces protein sumoylation, the targets and roles of sumoylation are largely unknown. Here, we found that cells exhibit a transient sumoylation response after exposure of cells to ≤ 7.5% volume/volume ethanol. The response peaks at 15 minutes and resolves by 60 minutes, indicating that cells have an adaptive response to low concentrations of ethanol. By contrast, the sumoylation response becomes chronic at 10% ethanol stress with no resolution by 60 minutes. To identify key targets of ethanol-induced sumoylation, we performed mass spectrometry analyses and identified 18 proteins with increased sumoylation after acute ethanol exposure, with 15 identified as known chromatin-associated proteins. Two of these proteins are the chromatin structural proteins Smc5 and Smc6, which are sumoylated by the activity of the SUMO ligase Mms21. Ethanol-induced Smc5/6 sumoylation occurs during G1 and G2M phases of the cell cycle but is abrogated during S phase despite the fact that other proteins are sumoylated during this phase. Acute ethanol exposure leads to formation of Rad52 foci indicating DNA damage similar to that observed with the addition of methyl methanesulfonate (MMS), which is an alkylating agent that damages DNA. Whereas MMS exposure induces the intra-S phase DNA damage checkpoint as observed by Rad53 phosphorylation, ethanol exposure does not induce the intra-S phase checkpoint and prevents Rad53 phosphorylation when added with MMS. From these results, we propose that ethanol induces a structural change in chromatin, possibly through DNA damage, and this causes sumoylation of conserved chromatin-associated proteins, including Smc5 and Smc6.
Hyperoxia inhibits proliferation of retinal endothelial cells in Myc dependent manner
Authors: Singh Charandeep , Benos Andrew , Grenell Allison , Rao Sujata , Anand-Apte Bela , Sears Jonathan E.
Published: November 2020

Oxygen supplementation is necessary to prevent mortality of severely premature infants. However, the supraphysiological concentration of oxygen utilized in these infants simultaneously creates retinovascular growth attenuation and vasoobliteration that induces retinopathy of prematurity. Here, we report that hyperoxia regulates the cell cycle and retinal endothelial cell proliferation in a previously unknown Myc dependent manner which contributes to oxygen-induced retinopathy.
A plant lipocalin is required for retinal-mediatedde novoroot organogenesis
Authors: Dickinson Alexandra J. , Zhang Jingyuan , Luciano Michael , Wachsman Guy , Schnermann Martin , Dinneny José R. , Benfey Philip N.
Published: November 2020

Branching of root systems enables the exploration and colonization of the soil environment. In Arabidopsis roots,de novoorganogenesis of lateral roots is patterned by an oscillatory mechanism called the root clock, which is dependent on metabolites derived from the β-carotene pathway1, 2. Retinoids are β-carotene-derived regulators of organogenesis in the animal kingdom. To determine if retinoids function in plant development, we conducted time-lapse imaging of a chemical reporter for retinoid binding proteins. We found that it oscillates with a comparable frequency to the root clock and accurately predicts sites of lateral root organogenesis. Exogenous application of retinal to wild-type plants is sufficient to induce root clock oscillations and lateral root organogenesis. A homology search yielded a potentialArabidopsishomolog, TEMPERATURE INDUCED LIPOCALIN (TIL) to vertebrate retinoid binding proteins. Genetic analysis indicates that TIL is necessary for normal lateral root development and atilmutant has decreased retinal sensitivity. TIL expression in a heterologous system conferred retinal binding activity, suggesting that it may directly interact with this molecule. Together, these results demonstrate an essential role for retinal and for plant retinal binding proteins in lateral root organogenesis.
Estimation of non-additive genetic variance in human complex traits from a large sample of unrelated individuals
Authors: Hivert Valentin , Sidorenko Julia , Rohart Florian , Goddard Michael E , Yang Jian , Wray Naomi R , Yengo Loic , Visscher Peter M
Published: November 2020

Non-additive genetic variance for complex traits is traditionally estimated from data on relatives. It is notoriously difficult to estimate without bias in non-laboratory species, including humans, because of possible confounding with environmental covariance among relatives. In principle, non-additive variance attributable to common DNA variants can be estimated from a random sample of unrelated individuals with genome-wide SNP data. Here, we jointly estimate the proportion of variance explained by additive, dominanceand additive-by-additivegenetic variance in a single analysis model. We first show by simulations that our model leads to unbiased estimates and provide new theory to predict standard errors estimated using either least squares or maximum likelihood. We then apply the model to 70 complex traits using 254,679 unrelated individuals from the UK Biobank and 1.1M genotyped and imputed SNPs. We found strong evidence for additive variance (average across traits. In contrast, the average estimate ofacross traits was 0.001, implying negligible dominance variance at causal variants tagged by common SNPs. The average epistatic varianceacross the traits was 0.058, not significantly different from zero because of the large sampling variance. Our results provide new evidence that genetic variance for complex traits is predominantly additive, and that sample sizes of many millions of unrelated individuals are needed to estimate epistatic variance with sufficient precision.
Computationally-guided design and affinity improvement of a protein binder targeting a specific site on HER2
Authors: Kim Tae Yoon , Cha Jeong Seok , Kim Hoyoung , Choi Yoonjoo , Cho Hyun-Soo , Kim Hak-Sung
Published: November 2020

A protein binder with a desired epitope and binding affinity is critical to the development of therapeutic agents. Here we present computationally-guided design and affinity improvement of a protein binder recognizing a specific site on domain IV of human epidermal growth factor receptor 2 (HER2). As a model, a protein scaffold composed of Leucine-rich repeat (LRR) modules was used. We designed protein binders which appear to bind a target site on domain IV using a computational method. Top 10 designs were expressed and tested with binding assays, and a lead with a low micro-molar binding affinity was selected. Binding affinity of the selected lead was further increased by two-orders of magnitude through mutual feedback between computational and experimental methods. The utility and potential of our approach was demonstrated by determining the binding interface of the developed protein binder through its crystal structure in complex with the HER2 domain IV.
B-1 lymphoid cells develop independently of Notch signaling during mouse embryonic development
Authors: Azevedo Nathalia , Bertesago Elisa , Ismailoglu Ismail , Kyba Michael , Kobayashi Michihiro , Ditadi Andrea , Yoshimoto Momoko
Published: November 2020

Thein vitrogeneration from pluripotent stem cells (PSCs) of different blood cell types, in particular those that are not replenished by hematopoietic stem cells (HSCs) like fetal-derived tissue-resident macrophages and innate-like lymphocytes, is of a particular interest. In order to succeed in this endeavor, a thorough understanding of the pathway interplay promoting lineage specification for the different blood cell types is needed. Notch signaling is essential for the HSC generation and their derivatives, but its requirement for tissue-resident immune cells is unknown. Using mouse embryonic stem cells (mESCs) to recapitulate murine embryonic development, we have studied the requirement for Notch signaling during the earliest B-lymphopoiesis and found thatRbpj-deficient mESCs are able to generate B-1 cells. Their Notch-independence was confirmed inex vivoexperiments usingRbpj-deficient embryos. In addition, we found that upregulation of Notch signaling was needed for the emergence of B-2 lymphoid cells. Taken together, these findings indicate that control of Notch signaling dosage is critical for the different B-cell lineage specification and provides pivotal information for theirin vitrogeneration from PSCs for therapeutic applications.
CGGBP1-dependent CTCF-binding sites restrict ectopic transcription
Authors: Patel Divyesh , Patel Manthan , Datta Subhamoy , Singh Umashankar
Published: November 2020

Binding sites of the chromatin regulator protein CTCF function as important landmarks in the human genome. The recently characterized CTCF-binding sites at LINE-1 repeats depend on another repeat-regulatory protein CGGBP1. These CGGBP1-dependent CTCF-binding sites serve as potential barrier elements for epigenetic marks such as H3K9me3. Such CTCF-binding sites are associated with asymmetric H3K9me3 levels as well as RNA levels in their flanks. The functions of these CGGBP1-dependent CTCF-binding sites remain un-known. By performing targeted studies on candidate CGGBP1-dependent CTCF-binding sites cloned in an SV40 promoter-enhancer episomal system we show that these regions act as inhibitors of ectopic transcription from the SV40 promoter. CGGBP1-dependent CTCF-binding sites that recapitulate their genomic function of loss of CTCF binding upon CGGBP1 depletion and H3K9me3 asymmetry in immediate flanks are also the ones that show the strongest inhibition of ectopic transcription. By performing a series of strand-specific reverse transcription PCRs we demonstrate that this ectopic transcription results in the synthesis of RNA from the SV40 promoter in a direction opposite to the downstream reporter gene in a strand-specific manner. The unleashing of the bidirectionality of the SV40 promoter activity and a breach of the transcription barrier seems to depend on depletion of CGGBP1 and loss of CTCF binding proximal to the SV40 promoter. RNA-sequencing reveals that CGGBP1-regulated CTCF-binding sites act as barriers to transcription at multiple locations genomewide. These findings suggest a role of CGGBP1-dependent binding sites in restricting ectopic transcription.
Plasticity after cortical stroke involves potentiating responses of pre-existing circuits but not functional remapping to new circuits
Authors: Zeiger William A , Marosi Máté , Saggi Satvir , Noble Natalie , Samad Isa , Portera-Cailliau Carlos
Published: November 2020

Functional recovery after stroke is thought to be mediated by adaptive circuit plasticity, whereby surviving neurons assume the roles of those that died. This “remapping” hypothesis is based on human brain mapping studies showing apparent reorganization of cortical sensorimotor maps and animal studies documenting molecular and structural changes that could support circuit rewiring. However, definitive evidence of remapping is lacking, and other studies have suggested that maladaptive plasticity mechanisms, such as enhanced inhibition in peri-infarct cortex, might actually limit plasticity after stroke. Here we sought to directly test whether neurons can change their response selectivity after a stroke that destroys a single barrel (C1) within mouse primary somatosensory cortex. Using multimodal in vivo imaging approaches, including two-photon calcium imaging to longitudinally record sensory-evoked activity in peri-infarct cortex before and after stroke, we found no evidence to support the remapping hypothesis. In an attempt to promote plasticity via rehabilitation, we also tested the effects of forced use therapy by plucking all whiskers except the C1 whisker. Again, we failed to detect an increase in the number of C1 whisker-responsive neurons in surrounding barrels even 2 months after stroke. Instead, we found that forced use therapy potentiated sensory-evoked responses in a pool of surviving neurons that were already C1 whisker responsive by significantly increasing the reliability of their responses. Together, our results argue against the long-held theory of functional remapping after stroke, but support a plausible circuit-based mechanism for how rehabilitation may improve recovery of function.
Novelty Processing Depends on Medial Temporal Lobe Structures
Authors: Schomaker J. , Grouls M.M.E. , Rau E. , Hendriks M. , Colon A. , Meeter M.
Published: November 2020

Objectives

The goal of the present study was to identify the role of the medial temporal lobe (MTL) in the detection and later processing of novelty stimuli.

Methods

Twenty-one epilepsy patients with unilateral MTL resection (10 left-sided; 11 right-sided) performed an adapted visual novelty oddball task. In this task two streams of stimuli were presented on the left and right of fixation while the patients’ electroencephalogram was measured. Patients responded to infrequent target stimuli, while ignoring frequent standard, and infrequent novel stimuli that could appear either contra- or ipsilateral to the resected side.

Results

Novelty detection, as indexed by the N2 ERP component elicited by novels, was not affected by the MTL resections. Later processing of novels, however, as indexed by the novelty P3 ERP component, was reduced for novels presented contra-versus ipsilateral to the resected side. Target processing, as indexed by the P3b, was unaffected.

Conclusions

The current results suggest that MTL structures play a role in novelty processing, but that the novelty signal may originate from a distinct neural source.
A Structural Ensemble of a Tau-Microtubule Complex Reveals Regulatory Tau Phosphorylation and Acetylation Mechanisms
Authors: Brotzakis Z. Faidon , Lindstedt Philip R. , Taylor Ross , Bernardes Gonçalo J. L. , Vendruscolo Michele
Published: November 2020

Tau is a microtubule-associated protein that regulates the stability of microtubules. The affinity of tau for microtubules is modulated by post-translational modifications, and the dysregulation of these events has been associated with the aberrant aggregation of tau in Alzheimer's disease and related tauopathies. Here, we use the metainference cryo-electron microscopy approach to determine an ensemble of structures representing the structure and dynamics of a tau-microtubule complex comprising an extended microtubule-binding region of tau (residues 202-395). We thus identify the ground state of the complex and a series of excited states of lower populations. An analysis of the interactions in these states of structures reveals positions in the tau sequence that are important to determine the overall stability of the tau-microtubule complex. This analysis leads to the identification of positions where phosphorylation and acetylation events have destabilising effects, which we validate by using site-specific post-translationally modified tau variants obtained by chemical mutagenesis. Taken together, these results illustrate how the simultaneous determination of ground and excited states of macromolecular complexes reveals functional and regulatory mechanisms.
Neuronal Activity-Dependent Accumulation of Arc in Astrocytes
Authors: Jiang Yuheng , VanDongen Antonius M.J.
Published: November 2020

The immediate-early gene Arc is a master regulator of synaptic plasticity and plays a critical role in memory consolidation. However, there has not been a comprehensive analysis of the itinerary of Arc protein, linking its function at different subcellular locations with corresponding time points after neuronal network activation. When cultured hippocampal neurons are treated with a combination of pharmacological agents to induce long term potentiation, they express high levels of Arc, allowing to study its spatiotemporal distribution. Our experiments show that neuronal activity-induced Arc expression was not restricted to neurons, but that its spatiotemporal dynamics involved a shift to astrocytes at a later timepoint. Specifically, astrocytic Arc is not due to endogenous transcription, but is dependent on the production of neuronal Arc and accumulates potentially via the recently reported intercellular transfer mechanism through Arc capsids. In conclusion, we found that Arc accumulates within astrocytes in a neuronal activity-dependent manner, which is independent of endogenous astrocytic Arc transcription, therefore highlighting the need to study the purpose of this pool of Arc, especially in learning and memory.
“Recalling hidden harms”: autistic experiences of childhood applied behavioural analysis (ABA)
Authors: McGill Owen , Robinson Anna
Published: November 2020

Purpose

This paper aims to investigate the long-term impacts autistic adults experienced from childhood participation in the applied behavioural analysis (ABA).

Design/methodology/approach

Possible participants were recruited through advertisements on social media and autism and ABA organisations. Possible participants were given the choice between an online or face-to-face interview or an anonymised online questionnaire.

Findings

Reflections from 10 participants were indicative of a predominantly detrimental impact of ABA. Reflections gave rise to a core theme “recalling hidden harms of childhood experiences of ABA”. Outcomes are discussed in relation to the impact on autistic identity, current research and progressing understanding of the impacts of early intervention from the autistic perspective.

Research limitations/implications

The practical implications of ABA are discussed alongside recommendations for future practice and research with the involvement of autistic individuals within interventive processes.

Originality/value

This is the first paper to take an in-depth, qualitative approach to autistic experiences of ABA. The findings themselves are driven to conceptualise and give voice to the core impacts which carried through participants’ exploration and understanding of self.
Effects of job autonomy on workplace loneliness among knowledge workers
Authors: Wang Diyang , Liu Hong
Published: November 2020

Purpose

Given its detrimental implications for employees’ well-being and work performance, this paper seeks to understand how workplace loneliness occurs by focusing on a job-related antecedent, job autonomy. Drawing on role identity theory and situational strength theory, the purpose of this paper is to propose that job autonomy relates to workplace loneliness via perceived insider status, a process moderated by perceived clan culture.

Design/methodology/approach

A two-wave survey served to collect data from 430 knowledge workers in 17 enterprises from several major cities in Eastern China.

Findings

Job autonomy relates to workplace loneliness via the mediation of perceived insider status. Specifically, job autonomy impacts positively on perceived insider status, which further reduces workplace loneliness. Besides, the relationship between perceived insider status and workplace loneliness is conditional on perceived clan culture – perceived insider status decreases workplace loneliness more effectively in the case of higher perceived clan culture. Furthermore, perceived clan culture moderates the mediating effect of perceived insider status.

Originality/value

This paper is among the few attempts to offer a comprehensive framework in which job and organizational characteristics combine to explain workplace loneliness. Moreover, the findings illustrate that perceived insider status and perceived clan culture complement each other in alleviating workplace loneliness.
Distributed leadership and organizational commitment: moderating role of confidence and affective climate
Authors: Ben Sedrine Sinda , Bouderbala Amel Sabra , Hamdi Myryam
Published: November 2020

Purpose

The purpose of this study is to examine the effect of distributed leadership on organizational commitment and the role of trust and open group climate as moderator variables in this relationship.

Design/methodology/approach

To test the conceptual model and research hypotheses empirically, the authors collected data based on an investigation over a sample of 318 engineers in the Information Technology telecommunication sector in Tunisia. The results were analyzed using factor analysis and structural equation modeling.

Findings

The results show a significant and positive impact of the support function, of the participation in decision-making and cooperation on organizational commitment. The authors find evidence for the existence of a positive moderating effect of trust and affective climate at the level of the causal link between distributed leadership and organizational commitment dimensions.

Research limitations/implications

These results provide useful indications for managers within the framework of leadership style that is more appropriate to the group’s proper functioning. Throughout this work, managers will know that distributed leadership is adapted to create a social climate based on dialogue and trust, an essential element of distributed leadership. Supervision and authority should give up a coercive vision in a more cooperative and constructive approach. Coordination should be founded on a horizontal and transversal vision of the organization.

Originality/value

Distributed leadership is increasingly seen as a key vehicle for firms’ improvement and renewal. However, research on this concept was largely conducted in the field of education and health. Studies dealing with small and medium-sized companies are rather scarce. There are not, to the best of the authors’ knowledge, any works in the Tunisian context because the majority of the reference studies are Anglo-Saxon. The originality and value of this research lies in its anchoring in the context. Moreover, this study provides empirical evidence of the importance of the role of the affective climate on organizational commitment. Indeed, engagement is a behavioral and attitudinal indicator of organizational climate. This paper is intended to provide a stimulus for exploring the distributed leadership area in terms of shaping thinking and designs for organizational change to enhance organizational commitment in a highly digital world.
Effects of zakat on the economic growth in selected Islamic countries: empirical evidence
Authors: Ben Jedidia Khoutem , Guerbouj Khouloud
Published: November 2020

Purpose

This study aims to examine the impact of zakat on the economic growth for a sample of Muslim countries. As a matter of fact, Zakat is a religious tax on wealth paid annually to specified recipients. As it leads to income redistribution and increases the aggregate demand, zakat can be a growth factor in the Islamic framework.

Design/methodology/approach

This paper is based on a dynamic panel data model for the purpose of investigating the role of zakat in the economic growth for a sample of eight Muslim countries during the period ranging from 2004 to 2017. The general method of moments is applied.

Findings

The findings provide evidence that zakat stimulates the country’s growth. Indeed, as zakat funds are directed to increase consumption, investment or government expenditure, they spur on the economic growth. Moreover, the authors come to the conclusion that more trade openness allows an increase in the real gross domestic product (GDP) per capita. However, the broad money to GDP and population growth rate seem insignificantly associated with the economic growth for the sample considered.

Practical implications

The findings have substantial implications for the economic policy in Muslim countries. Authorities may further rely on zakat to boost the economic growth. First, it is essential to improve the muzakki’s knowledge on zakat to increase their intention, and so their ability and willingness to pay zakat. Second, the government intervention in both zakat collect and distribution becomes mandatory. Therefore, the contribution of zakat to the economic growth will be higher. This requires better-quality services of zakat institutions.

Originality/value

A few studies have empirically looked into the impact of zakat on the economic growth, especially for panel data. Hence, the present study tries to enrich the literature on this topic. It creates significant evidence regarding the relevance of zakat in Muslim countries. The findings provide empirical support that zakat is an additional growth factor in the Islamic framework.
Coronavirus containment depends on human rights: freedom of expression and press are needed to fight pandemic
Authors: Altshuler Ellery
Published: November 2020

Purpose

The purpose of this paper is to describe restrictions on freedoms of expression and press that have arisen during the coronavirus pandemic and to show the public health impact of these restrictions.

Design/methodology/approach

General PubMed and Google searches were used to review human rights violations both historically and during the current coronavirus pandemic. Special attention was paid to publications produced by groups dedicated to monitoring human rights abuses.

Findings

During the coronavirus pandemic, many governments have used the guise of controlling the virus to silence critics and stifle the press. Though these restrictions were supposedly orchestrated to fight the virus, they have done just the opposite: suppression of expression and press has hindered public health efforts and exacerbated the spread of the virus. By reducing case reporting, allowing for the spread of misinformation and blocking productive debate, violations of human rights to free expression and press have worsened the coronavirus outbreak.

Originality/value

This study shows the ways in which human rights are both threatened and particularly important in crises.
When workplace bullying spreads workplace deviance through anger and neuroticism
Authors: Jahanzeb Sadia , Fatima Tasneem , De Clercq Dirk
Published: November 2020

Purpose

With a basis in affective events theory, this study aims to investigate the mediating role of anger in the relationship between employees’ exposure to workplace bullying and their engagement in deviant behaviours, as well as the invigorating role of their neuroticism in this process.

Design/methodology/approach

Three-wave, time-lagged data were collected from employees and their peers in a sample of Pakistani organizations.

Findings

Workplace bullying spurs interpersonal and organizational deviance because it prompts feelings of anger in employees. This mechanism is more prominent among employees with high levels of neuroticism.

Originality/value

This study reveals that the experience of anger is a key feature by which bullying behaviours steer employees towards counterproductive work behaviours, and this harmful process is more likely to escalate when employees’ personality makes them more vulnerable to emotional distress.
Corruption and innovation: the importance of competition
Authors: Karaman Kabadurmus Fatma Nur , Sylwester Kevin
Published: November 2020

Purpose

The purpose of this study is to examine how corruption affects the prevalence of product and process innovation by firms.

Design/methodology/approach

This study uses firm-level data from the 2012–2016 Business Environment Enterprise Performance Surveys and utilizes a conditional mixed process model to address endogeneity concerns, taking bribery as a measure of corruption.

Findings

The study shows that measures of bribery are positively and robustly associated with innovation but mainly for firms reporting many competitors. The results are stronger for firms reporting more obstacles. Both findings support the inference that bribes facilitate innovation by allowing firms to evade regulatory obstacles.

Originality/value

The current research on corruption's effect on innovation restricts the association to be uniform across the sample, but this study shows that the impact depends on the degree of competition faced by a firm. In addition, the data used in this study cover 30 economies in Eastern Europe and Central Asia, and thus contributes to determining the effects of anticorruption practices in emerging countries.