bluuebunny/crossref_metadata_2025 huggingface dataset:
Ensemble encoding of conditioned fear by prefrontal somatostatin interneurons
Authors: Cummings Kirstie A. , Bayshtok Sabina , Kenny Paul J. , Clem Roger L.
Published: July 2021

Neurons preferentially activated by learning have been ascribed the unique potential to encode memory. However, it remains unclear which genetically-defined cell types are recruited as part of such an ensemble, or what role discrete subpopulations play in behavior. Here we show that fear conditioning activates a heterogeneous neural ensemble in the medial prefrontal cortex (mPFC), comprised to a large degree of GABAergic interneurons immunoreactive for somatostatin (SST-INs). Using an intersectional genetic approach, we demonstrate that fear learning-activated SST-INs exhibit distinct circuit properties, are preferentially reactivated during memory retrieval, and mediate the expression of defensive freezing. We further show that a rewarding experience, morphine treatment, activates an orthogonal SST-IN population that exerts opposing control over fear. These results outline an important role for discrete GABAergic ensembles in fear memory encoding, and point to an unappreciated capacity for functional specialization among SST-INs.
Docking Molecular analysis of potential Aldosterone antagonists
Authors: Ferrari Ivan Vito , Patrizio Paolo
Published: July 2021

Background

Aldosterone antagonists (spironolactone, eplerenone) inhibit the action of aldosterone in the collecting duct; as such, these agents cause modest diuresis but inhibit potassium and hydrogen ion secretion. We report first time Potential Aldosterone antagonists by in Silico approach, using AutoDock Vina and AutoDock 4 (or MGL Tool), estimated with Pyrx and AM Dock Software, calculating three different important parameters: Binding Affinity (kcal/mol), estimated Ki (in nM units) and Ligand Efficiency (L.E. in kcal/mol). After a selective analysis of over 1000 drugs, processed with Pyrx (a Virtual Screening software for Computational Drug Discovery) in the Ligand Binding site pocket of the protein (ID PDB 2OAX Chain A:), we noticed high values of Binding Energy, about −13.55 kcal/mol estimated by AutoDock 4 with AM Dock Software, concluding that it could be an excellent candidate drug, compared to everyone else Aldosterone antagonists. Indeed, from the results of AutoDock Vina and AutoDock 4 (or AutoDock 4.2), implemented with Lamarckian genetic algorithm, LGA, trough AMDock Software, our results of Binding Energy are very similar to the crystallized Spironolactone in PDB 2OAX Chain A protein.
X upregulation is not global and extent of upregulation differs between ancestral and acquired X-linked genes
Authors: Naik C H , Hari K , Chandel D , Jolly MK , Gayen S
Published: July 2021

Evolution of sex chromosome dosage compensation in mammals remains poorly understood. Ohno’s hypothesis state that evolution of dosage compensation occurred through two steps: first, to compensate the dosage imbalance created due to the degradation of Y chromosome in male, upregulation of X-chromosome happened. Subsequently, transmission of X-chromosome upregulation (XCU) in female led to the evolution of X-chromosome inactivation (XCI) to counteract extra dosage of X-linked genes in female cells. Here, we have profiled gene-wise dynamics of XCU in pre-gastrulation mouse embryos at single cell level and found that XCU is dynamically linked with XCI, however, XCU is not global or chromosome-wide like XCI. Therefore, our result raises question whether XCU driven the evolution of XCI. If so, then why XCI is chromosome wide while XCU is not. We propose that XCI might have evolved independent of XCU and therefore refining the current model is necessary. Separately, we show that higher occupancy of different activating factors at upregulated X-linked genes leads to enhanced transcriptional burst frequency and thereby leads to upregulation. On the other hand, our analysis indicates that extent of upregulation, enrichment of different activating marks differs between ancestral and newly acquired X-linked genes. Altogether, our study provides significant insight into the dynamics and mechanistic basis of evolution of sex chromosome dosage compensation.

Abstract Figure
Pleiotropic Variability Score: A Genome Interpretation Metric to Quantify Phenomic Associations of Genomic Variants
Authors: Shameer Khader , Glicksberg Benjamin S. , Badgeley Marcus A. , Johnson Kipp W. , Dudley Joel T.
Published: July 2021

A more complete understanding of phenomic space is critical for elucidating genome-phenome relationships and for assessing disease risk from genome sequencing. To incorporate knowledge of how related a variant’s associations are, we developed a new genome interpretation metric called Pleiotropic Variability Score (PVS). PVS uses semantic reasoning to score the relatedness of a genetic variant’s associated phenotypes based on those phenotypes’ relationships in the human phenotype ontology (HPO) and disease ontology (DO). We tested 78 unique semantic similarity methods and integrated six robust metrics to define the pleiotropy score of SNPs. We computed PVS for 12,541 SNPs which were mapped to 382 HPO and 317 DO unique phenotype terms in a genotype-phenotype catalog (10,021 SNPs mapped to DO phenotypes and 8,569 SNPs mapped to HPO phenotypes). We validated the utility of PVS by computing pleiotropy using an electronic health record linked genomic database (BioME, n=11,210). Further we demonstrate the application of PVS in personalized medicine using “personalized pleiotropy score” reports for individuals with genomic data that could potentially aid in variant interpretation. We further developed a software framework to incorporate PVS into VCF files and to consolidate pleiotropy assessment as part of genome interpretation pipelines. As the genome-phenome catalogs are growing, PVS will be a useful metric to assess genetic variation to find SNPs with highly pleiotropic effects. Additionally, variants with varying degree of pleiotropy can be prioritized for explorative studies to understand specific roles of SNPs and pleiotropic hubs in mediating novel phenotypes and drug development.
Facultative variation across a shallow to deep torpor spectrum in hummingbirds
Authors: Shankar A , Cisneros INH , Thompson S , Graham CH , Powers DR
Published: July 2021

Many small endotherms use torpor, saving energy by a controlled reduction of their body temperature and metabolic rate. Some species (e.g. arctic ground squirrels, hummingbirds) enter deep torpor, dropping their body temperatures by 23-37 °C, while others can only enter shallow torpor (e.g., pigeons, 3-10 °C reductions). However, deep torpor in mammals can increase predation risk (unless animals are in burrows or caves), inhibit immune function, and result in sleep deprivation, so even for species that can enter deep torpor, facultative shallow torpor might help balance energy savings with these potential costs. Deep torpor occurs in three avian orders. Although the literature hints that some bird species can use both shallow and deep torpor, little empirical evidence of such an avian torpor spectrum exists. We infrared imaged three hummingbird species that are known to use deep torpor, under natural temperature and light cycles, to test if they were also capable of shallow torpor. All three species used both deep and shallow torpor, often on the same night. Depending on the species, they used shallow torpor for 5-35% of the night. The presence of a bird torpor spectrum indicates a capacity for fine-scale physiological and genetic regulation of avian torpid metabolism.
EEG biomarkers of reduced inhibition in human cortical microcircuits in depression
Authors: Mazza Frank , Valiante Taufik A. , Griffiths John D. , Hay Etay
Published: July 2021

Reduced cortical inhibition by somatostatin-expressing (SST) interneurons has been strongly associated with treatment-resistant depression. However, whether the effects of reduced SST interneuron inhibition on microcircuit activity have signatures detectible in electroencephalography (EEG) signals remains unknown. We simulated resting-state activity and EEG using detailed models of human cortical microcircuits with normal (healthy) or reduced SST interneuron inhibition (depression). Healthy microcircuit models showed emergent key features of resting-state EEG, and depression microcircuits exhibited increased theta, alpha and low beta power (4 – 15 Hz). The changes in depression involved a combination of an aperiodic broadband, and periodic theta components. We then demonstrated the specificity of the EEG signatures of reduced SST interneuron inhibition by showing they were distinct from those corresponding to reduced parvalbumin-expressing (PV) interneuron inhibition. Our study thus links SST interneuron inhibition level to distinct features in EEG simulated from detailed human microcircuits, which can serve to better identify mechanistic subtypes of depression using EEG, and non-invasively monitor modulation of cortical inhibition.
FMRP regulates mRNAs encoding distinct functions in the cell body and dendrites of CA1 pyramidal neurons
Authors: Hale Caryn R. , Sawicka Kirsty , Mora Kevin , Fak John , Kang Jin Joo , Cutrim Paula , Cialowicz Katarzyna , Carroll Thomas , Darnell Robert B.
Published: July 2021

Neurons are believed to rely on dendritic localization and translation of mRNAs in order to generate activity-dependent changes in the synaptic plasticity. Here, we develop a strategy combining compartment-specific CLIP and TRAP in conditionally tagged mice to precisely define the ribosome-bound dendritic transcriptome of CA1 pyramidal neurons. This revealed transcripts that have differentially localized alternative 3’UTR and splicing isoforms. FMRP targets are overrepresented among dendritic mRNAs, and compartment-specific FMRP-CLIP defined 383 dendritic FMRP targets, and also allowed for segregation of whole-cell FMRP targets into functional modules that are locally regulated by FMRP. In the absence of FMRP, dendritic FMRP targets show increased ribosome association, consistent with reported roles for FMRP in translational repression. Together, the data support a model in which distinct patterns of FMRP localization allow it to differentially regulate the expression of nuclear proteins and synaptic proteins within different compartments of a single neuronal cell type.
The genomic formation of Tanka people, an isolated 'Gypsies in water' in the coastal region of Southeast China
Authors: He Guanglin G , Zhang Yunhe , Wei Lan-Hai , Wang Mengge , Yang Xiaomin , Guo Jianxin , Hu Rong , Wang Chuan-Chao , Zhang Xian-Qing
Published: July 2021

Objectives: Three different hypotheses proposed via the controversial evidence from cultural, anthropological and uniparental genetic analysis respectively stated that Tanka people probably originated from Han Chinese, ancient Baiyue tribe, or the admixture of them. Therefore, the genetic origin and admixture history of the Tanka people, an isolated 'Gypsies in water' in the coastal region of Southeast China, are needed to be genetically clarified. Materials and methods: To elucidate the genetic origin of the Southeast Tanka people and explore their genetic relationship with surrounding indigenous Tai-Kadai and Austronesian people and Neolithic-to-historic ancients from the Yellow River Basin (YRB) and Fujian, we conducted a large-scale population genomic study among 1498 modern and ancient Eurasians, in which 73 Tanka and 4 Han people were first reported here. Both allele-shared and haplotype-based statistical methods were used here, including PCA, ADMIXTURE, f-statistics, ALDER, qpGraph-/TreeMix and qpAdm/qpWave, ChromoPainter and FineSTRUCTURE. Results: We found a specific genetic cline in PCA plots and detected the Tanka-specific homogeneous ancestry in model-based ADMIXTURE results, suggesting differentiated demographic history between Tanka and surrounding Hans. Formal tests based on sharing allele patterns showed a close relationship between Tanka people and Han Chinese, but the Tanka population harbored more southern East Asian ancestry related to Austronesian and Tai-Kadai people compared with southern Hans. Besides, the reconstructed differentiated demographic history revealed that southern Xinshizhou Tanka harbored more ancestry related to the Tai-Kadai or coastal ancient Neolithic to Bronze Age East Asians compared with northern Shacheng Tanka. The qpGraph-/TreeMix-based phylogenetic framework, qpAdm/qpWave-based admixture modeling and FineSTRUCTURE-based dendrogram among ancient northern and southern East Asians further demonstrated that the primary ancestry of modern Tanka derived from ancient millet farmers in the YRB with additional admixture from multiple southern East Asian sources. Discussion: Sharing ancestry estimated from the f-statistics and sharing haplotypic landscape inferred from the ChromoPainter and FineSTRUCTURE showed that Southeast Tanka people not only had a close genetic relationship with both Northern Hans and YRB millet farmers but also possessed more southern East Asian ancestry related to Austronesian, Tai-Kadai and Hmong-Mien people. Our genomic data and fitted admixture models supported modern Tanka originated from ancient North China and obtained additional gene flow from ancient southern East Asians in the processes of southward migrations.
Identifying Louisiana communities at the crossroads of environmental and social vulnerability, COVID-19, and asthma
Authors: Bakshi Arundhati , Van Doren Alicia , Maser Colette , Aubin Kathleen , Stewart Collette , Soileau Shannon , Friedman Kate , Williams Alexis
Published: July 2021

The COVID-19 pandemic has disproportionately affected the socially and environmentally vulnerable, including through indirect effects on other health conditions. Asthma is one such condition, which may be exacerbated by both prolonged adverse in-home exposures if quarantining in unhealthy homes and prolonged outdoor exposures if the ambient air quality is unhealthy or hazardous. As both are often the case in Environmental Justice (EJ) communities, here we have analyzed data at the census tract (CT) level for Louisiana to assess any correlation between social and environmental vulnerability, and health issues like COVID-19 and asthma. Higher Social Vulnerability Index (SVI), Particulate Matter less than 2.5 µm in diameter (PM2.5) and Ozone levels were associated with higher rates of cumulative COVID-19 incidence at various time points during the pandemic, as well as higher average annual asthma hospitalization rates and estimated asthma prevalence. Further, cumulative COVID-19 incidence during the first three months of the pandemic was moderately correlated with both asthma hospitalizations and estimated prevalence, suggesting similar underlying factors may be affecting both conditions. Additionally, 137 CTs were identified where social and environmental vulnerabilities co-existed, of which 75 (55%) had high estimated prevalence of asthma. These areas are likely to benefit from asthma outreach that considers both social and environmental risk factors. Fifteen out of the 137 CTs (11%) not only had higher estimated prevalence of asthma but also a high burden of COVID-19. Further research in these areas may help to elucidate any common social determinants of health that underlie both asthma and COVID-19 burdens, as well as better clarify the possible role of the environment as related to the COVID-19 burden in Louisiana.
Applying mixture model methods to SARS-CoV-2 serosurvey data from Geneva
Authors: Bouman Judith A , Kadelka Sarah , Stringhini Silvia , Pennacchio Francesco , Meyer Benjamin , Yerly Sabine , Kaiser Laurent , Guessous Idris , Azman Andrew S , Bonhoeffer Sebastian , Regoes Roland R
Published: July 2021

Serosurveys are an important tool to estimate the true extent of the current SARS-CoV-2 pandemic. So far, most serosurvey data have been analysed with cut-off based methods, which dichotomize individual measurements into sero-positives or negatives based on a predefined cutoff. However, mixture model methods can gain additional information from the same serosurvey data. Such methods refrain from dichotomizing individual values and instead use the full distribution of the serological measurements from pre-pandemic and COVID-19 controls to estimate the cumulative incidence. This study presents an application of mixture model methods to SARS-CoV-2 serosurvey data from the SEROCoV-POP study from April and May 2020 in Geneva (2766 individuals). Besides estimating the total cumulative incidence in these data (8.1% (95% CI: 6.8% - 9.8%)), we applied extended mixture model methods to estimate an indirect indicator of disease severity, which is the fraction of cases with a distribution of antibody levels similar to hospitalised COVID-19 patients. This fraction is 51.2% (95% CI: 15.2% - 79.5%) across the full serosurvey, but differs between three age classes: 21.4% (95% CI: 0% - 59.6%) for individuals between 5 and 40 years old, 60.2% (95% CI: 21.5% - 100%) for individuals between 41 and 65 years old and 100% (95% CI: 20.1% - 100%) for individuals between 66 and 90 years old. Additionally, we find a mismatch between the inferred negative distribution of the serosurvey and the validation data of pre-pandemic controls. Overall, this study illustrates that mixture model methods can provide additional insights from serosurvey data.
Public opinion on sharing data from UK health services for clinical and research purposes without explicit consent
Authors: Jones Linda A. , Nelder Jenny R. , Fryer Joseph M. , Alsop Philip H. , Geary Michael R. , Prince Mark , Cardinal Rudolf N.
Published: July 2021

1.

BACKGROUND

In the UK, National Health Service (NHS/HSC) data is variably shared between healthcare organizations for direct care, and increasingly used in de-identified forms for research. Few large-scale studies have examined public opinion on sharing, including the treatment of mental health (MH) versus physical health (PH) data.

METHODS

Pre-registered anonymous online survey open to all UK residents, recruiting Feb–Sep 2020. Participants were randomized to one of three framing statements regarding MH versus PH data.

FINDINGS

Participants numbered 29275; 40% had experienced a MH condition. A majority supported identifiable data sharing for direct clinical care without explicit consent, but 20% opposed this. Preference for clinical/identifiable sharing decreased with distance and was slightly less for MH than PH data, with a small framing effect. Preference for research/de-identified data sharing without explicit consent showed the same small PH/MH and framing effects, plus greater preference for sharing structured data than de-identified free text. There was net support for research sharing to the NHS, academic institutions, and national research charities, net ambivalence about sharing to profit-making companies researching treatments, and net opposition to sharing to other companies (similar to sharing publicly). De-identified linkage to non-health data was generally supported, except to data held by private companies. We report demographic influences on preference. A clear majority supported a single NHS mechanism to choose uses of their data. Support for data sharing increased during the pandemic.

INTERPRETATION

Support for healthcare data sharing for direct care without explicit consent is broad but not universal. There is net support for the sharing of de-identified data for research to the NHS, academia, and the charitable sector, but not the commercial sector. A single national NHS-hosted system for patients to control the use of their NHS data for clinical purposes and for research would have broad public support.

FUNDING

MRC.
Low seropositivity and sub-optimal neutralisation rates in patients fully vaccinated against COVID-19 with B cell malignancies
Authors: Fox TA , Kirkwood AA , Enfield L , O’Reilly M , Arulogun S , D’Sa S , O’Nions J , Kavi J , Vitsaras E , Townsend W , Burns SO , Gohil SH , Cwynarski K , Thomson KJ , Noursadeghi M , Heyderman RS , Rampling T , Ardeshna KM , McCoy LE , Morris EC
Published: July 2021

Patients with haematological malignancies are at increased risk of severe disease and death from COVID-19 and are less likely to mount humoral immune responses to COVID-19 vaccination, with the B cell malignancies a particularly high-risk group.

Our COV-VACC study is evaluating the immune response to COVID-19 vaccination in patients with B cell malignancies. Eligible patients were either receiving active treatment or had received treatment within the last 24 months. Patients were vaccinated with either the BNT162b2 (Pfizer-BioNTech) (n=41) or ChAdOx1 nCoV-19 (Oxford-AstraZeneca) (n=14) vaccines. The median age of participants was 60 years (range: 27-82) and 50% were receiving systemic anti-cancer therapy (SACT) at the time of vaccination. This interim analysis from the first 55 participants describes anti-S seropositivity rates, neutralising antibody activity and association with peripheral lymphocyte subsets.

After the first vaccine dose, 36% overall had detectable anti-S antibodies rising to 42% after the second dose. Sera from seropositive patients was assessed for neutralisation activity in vitro. Of the seropositive patients after first dose (n=17), only 41% were able to neutralise SARS-CoV-2 pseudotyped virus with a 50% inhibitory dilution factor (ID50) of >1:50. After two doses (n=21) 57% of the seropositive patients had detectable neutralisation activity (median ID50 of 1:469, range 1:70 – 1:3056). Total blood lymphocyte, CD19, CD4 and CD56 counts were significantly associated with seropositivity. Patients vaccinated more than 6 months after completing therapy were significantly more likely to develop antibodies than those within 6 months of treatment or on active treatment; OR: 5.93 (1.29 – 27.28).

Our data has important implications for patients with B cell malignancies as we demonstrate a disconnect between anti-S seropositivity and virus neutralisation in vitro following vaccination against COVID-19.

Urgent consideration should be given to revaccinating patients with B-cell malignancies after completion of anti-cancer treatment as large numbers currently remain at high risk of infection with the increasing transmission of SARS-CoV-2 in many countries.
Severe introduced predator impacts despite attempted functional eradication
Authors: Cheng Brian S , Blumenthal Jeffrey , Chang Andrew L , Barley Jordanna , Ferner Matthew C , Nielsen Karina J , Ruiz Gregory M , Zabin Chela J
Published: July 2021

Established non-native species can have significant impacts on native biodiversity without any possibility of complete eradication. In such cases, one management approach is functional eradication, the reduction of introduced species density below levels that cause unacceptable effects on the native community. Functional eradication may be particularly effective for species with limited dispersal ability, which may limit rates of reinvasion from distant populations. Here, we evaluate the potential for functional eradication of introduced predatory oyster drills (Urosalpinx cinerea) using a community science approach in San Francisco Bay. We combined observational surveys, targeted removals, and a caging experiment to evaluate the effectiveness of this approach in mitigating the mortality of prey Olympia oysters (Ostrea lurida), a conservation and restoration priority species. Despite the efforts of over 300 volunteers that removed over 30,000 oyster drills, we report limited success and discuss several possible mechanisms for this result with broad relevance to management for this and other introduced species. We also found a strong negative relationship between oyster drills and oysters, showing virtually no coexistence across eight sites. At two removal sites, there was no effect of oyster drill removal on oyster survival, which was only observed by caging treatment (0 and 1.6% survival in open and partial cage treatments, as compared to 89.1% in predator exclusion treatments). We conclude that functional eradication of this species requires significantly greater effort and may not be a viable management strategy. Oyster restoration efforts should not be undertaken where Urosalpinx is established or is likely to invade.
Vaccinia Virus Arrests and Shifts the Cell Cycle
Authors: Martin Caroline K. , Samolej Jerzy , Olson Annabel T. , Bertoli Cosetta , Wiebe Matthew S. , de Bruin Robertus A. M. , Mercer Jason
Published: July 2021

Modulation of the host cell cycle is a common strategy used by viruses to create a pro-replicative environment. To facilitate viral genome replication, vaccinia virus (VACV) has been reported to alter cell cycle regulation and trigger the host cell DNA damage response. However, the cellular factors and viral effectors that mediate these changes remain unknown. Here, we set out to investigate the effect of VACV infection on cell proliferation and host cell cycle progression. Using a subset of VACV mutants we characterize the stage of infection required for inhibition of cell proliferation and define the viral effectors required to dysregulate the host cell cycle. Consistent with previous studies, we show that VACV inhibits, and subsequently shifts the host cell cycle. We demonstrate that these two phenomena are independent of one another, with viral early genes being responsible for cell cycle inhibition, and post-replicative viral gene(s) responsible for the cell cycle shift. Extending previous findings, we show that the viral kinase F10 is required to activate the DNA damage checkpoint and that the viral B1/B12 (pseudo) kinases mediate degradation of checkpoint effectors p53 and p21 during infection. We conclude that VACV modulates host cell proliferation and host cell cycle progression through temporal expression of multiple VACV effector proteins.
Rhodanese Rdl2 produces reactive sulfur species to scavenge hydroxyl radical and protect mitochondria
Authors: Wang Qingda , Chen Zhigang , Zhang Xi , Xin Yuping , Xia Yongzhen , Xun Luying , Liu Huaiwei
Published: July 2021

During aerobic respiration, mitochondria generate superoxide anion (O2•−), hydrogen peroxide (H2O2), and hydroxyl radical (HO•), and these reactive oxygen species (ROS) are detrimental to mitochondria. Mitochondrial damage is linked to a broad spectrum of pathologies such as Alzheimer’s disease, hemochromatosis, and diabetes. Mitochondria contain several enzymes for rapidly removing superoxide anion and hydrogen peroxide, but how they antagonize HO• is elusive, representing a loophole in the anti-ROS system. Herein, we discovered that Rhodanese 2 (Rdl2) is critical for maintaining the functionality and integrity of mitochondria under sub-lethal ROS stress in Saccharomyces cerevisiae. Rdl2 converts stable sulfur species (thiosulfate and dialkyl polysulfide) to reactive sulfane sulfur including persulfide that protects mitochondrial DNA via scavenging HO•. Surprisingly, hydrogen sulfide (H2S) promotes HO• production through stimulating the Fenton reaction, leading to increased DNA damage. Our study may reveal an ex-ante mean for antagonizing HO•, patching the loophole of the anti-ROS system in mitochondria.
The critical modulatory role of spiny stellate cells in seizure onset based on dynamic analysis of a neural mass model
Authors: Tabatabaee Saba , Bahrami Fariba , Janahmadi Mahyar
Published: July 2021

Growing evidence suggests that excitatory neurons in the brain play a significant role in seizure generation. Nonetheless, spiny stellate cells are cortical excitatory non-pyramidal neurons in the brain, which their basic role in seizure occurrence is not well understood. In the present research, we study the critical role of spiny stellate cells or the excitatory interneurons (EI), for the first time, in epileptic seizure generation using an extended neural mass model inspired by Liu and Wang model in 2017. Applying bifurcation analysis on this modified model, we investigated the rich dynamics corresponding to the epileptic seizure onset and transition between interictal and ictal states caused by EI connectivity to other cell types. Our results indicate that the transition between interictal and ictal states (preictal signal) corresponds to a supercritical Hopf bifurcation, and thus, the extended model suggests that before seizure onset, the amplitude and frequency of neural activities gradually increase. Moreover, we showed that 1) the altered function of GABAergic and glutamatergic receptors of EI can cause seizure, and 2) the pathway between the thalamic relay nucleus and EI facilitates the transition from interictal to the ictal activity by decreasing the preictal period. Thereafter, we considered both sensory and cortical periodic inputs to study model responses to various harmonic stimulations. Bifurcation analysis of the model, in this case, suggests that the initial state of the model might be the main cause for the transition between interictal and ictal states as the stimulus frequency changes. The extended thalamocortical model shows also that the amplitude jump phenomenon and nonlinear resonance behavior result from the preictal state of the modified model. These results can be considered as a step forward to a deeper understanding of the mechanisms underlying the transition from normal activities to epileptic activities.
Parkinson' disease medication alters rat small intestinal motility and microbiota composition
Authors: van Kessel Sebastiaan P , Bullock Amber , van Dijk Gertjan , El Aidy Sahar
Published: July 2021

Parkinson's disease (PD) is known to be associated with altered gastrointestinal function and microbiota composition. Altered gastrointestinal function is key in the development of small intestinal bacterial overgrowth, which is a comorbidity often observed in PD patients. Although PD medication could be an important confounder in the reported alterations, its effect per se on the microbiota composition or the gastrointestinal function at the site of drug absorption has not been studied. To this end, healthy (i.e., not PD model) wild-type Groningen rats were employed and treated with dopamine, pramipexole (in combination with levodopa/carbidopa), or ropinirole (in combination with levodopa/carbidopa) for 14 sequential days. Rats treated with dopamine agonists showed a significant reduction in the small intestinal motility and an increase in bacterial overgrowth in the distal small intestine. Importantly, significant alterations in microbial taxa were observed between the treated and vehicle groups, analogous to the changes previously reported in human PD vs HC microbiota studies. These microbial changes included an increase in Lactobacillus and Bifidobacterium, and decrease in Lachnospiraceae and Prevotellaceae. Importantly, certain Lactobacillus species correlated negatively with the plasma levels of levodopa. Overall, the results highlight the significant effect of PD medication per se on the gut microbiota, and the disease-associated comorbidities, including gastrointestinal dysfunction and small intestinal bacterial overgrowth.
Fast and efficient CRISPR-mediated genome editing in Aureobasidium pullulans using Cas9 ribonucleoproteins
Authors: Kreuter Johanna , Stark Georg , Mach Robert L. , Mach-Aigner Astrid R. , Derntl Christian
Published: July 2021

Aureobasidium pullulans is a ubiquitous, polyextremotolerant, “yeast-like” ascomycete used for the industrial production of pullulan and other products and as biocontrol agent in the agriculture. Its application potential and its wide-spread occurrence make A. pullulans an interesting study object. The availability of a fast and efficient genome editing method is an obvious advantage for future basic and applied research on A. pullulans. In this study, we describe the development of a CRISPR/Cas9-based genome editing method using ribonucleoproteins (RNPs). We demonstrate that this method can be used for single and multiplex genome editing using only RNPs by targeting ura3 (encoding for orotidine-5′-phosphate decarboxylase), praics (encoding for phosphoribosyl aminoimidazole-succinocarboxamide synthase) and asl (encoding for arginine succinate lyase). We demonstrate the applicability of Trichoderma reesei pyr4 and Aspergillus fumigatus pyrG to complement the ura3 deficiency. Further, we show that the usage of RNPs can boost the homologous recombination rate up to nearly 100%, even when using only 20bp long homologous flanks. Therefore, the repair cassettes can be constructed by a single PCR, abolishing the need for laborious and time-consuming cloning. The here presented method allows fast and efficient genome editing for gene deletions, modifications, and insertions in A. pullulans.
Research trends analysis using text mining in construction management: 2000–2020
Authors: Bilge Eymen Çağatay , Yaman Hakan
Published: July 2021

Purpose

This study aims to identify the trends that have changed in the field of construction management over the last 20 years.

Design/methodology/approach

In this study, 3,335 journal articles published in the years 2000–2020 were collected from the Web of Science database in construction management. The authors applied bibliometric analysis first and then detected topics with the latent Dirichlet allocation (LDA) topic detection method.

Findings

In this context, 20 clusters from cluster analysis were found and the topics were extracted in clusters with the LDA topic detection method. The results show “building information modeling” and “information management” are the most studied subjects, even though they have emerged in the last 15 years “building information modeling,” “information management,” “scheduling and cost optimization,” “lean construction,” “agile approach” and “megaprojects” are the trend topics in the construction management literature.

Research limitations/implications

This study uses bibliometric analysis. The authors accept that the co-citation and co-authorship relationship in the data is ethical. They accept that honorary authorship, self-citation or honorary citation do not change the pattern of the construction management research domain.

Originality/value

There has been no study conducted in the last 20 years to examine research trends in construction management. Although bibliometric analysis, systematic literature reviews and text mining methods are used separately as a methodology for extracting research trends, no study has used enhanced bibliometric analysis and the LDA topic detection text mining method.
Critical success factors for BIM adoption during construction phase: a Singapore case study
Authors: Liu Ziwen , Lu Yujie , Nath Tushar , Wang Qian , Tiong Robert Lee Kong , Peh Luke Lu Chang
Published: July 2021

Purpose

As a pillar of integrated digital delivery (IDD), building information modeling demonstrates the tremendous potential to enhance productivity for the architectural, engineering and construction (AEC) industry worldwide. However, the implementation of digital solutions presents numerous challenges related to its adoption and implementation. Distinguishing a comprehensive set of critical factors can facilitate the construction professionals to execute their strategies in a properly planned manner, thus augmenting the possibilities of successfully implementing BIM in their organization. This study aims to identify critical success factors (CSFs) for BIM adoption and implementation in Singapore.

Design/methodology/approach

This study adopted structured empirical questionnaire survey. Relevant data were collected from the various stakeholders in Singapore AEC industry through an online survey questionnaire. Furthermore, data analysis was done using SPSS Statistics software in order to identify the key factors (KFs) based on which the CSFs were derived for BIM adoption and implementation during the construction phase.

Findings

From a set of 45 influencing factors, 35 KFs were derived after performing ranking analysis, from which a set of 26 CSFs were finally obtained based on the factor analysis methodology.

Originality/value

This study has identified the CSFs of BIM adoption in Singapore, as well as in the builders' perspective on how to enhance the digitalization in construction projects.
Getting involved in innovation: how High-Involvement HRM practices support employee’s to be innovative
Authors: Beddow Helen
Published: July 2021

Purpose

This paper aims to review the latest management developments across the globe and pinpoint practical implications from cutting-edge research and case studies.

Design/methodology/approach

This briefing is prepared by an independent writer who adds their own impartial comments and places the articles in context.

Findings

Based on research from the manufacturing industry in Pakistan, the authors find that high-involvement HR practices have a direct positive impact on individual employee functional flexibility and innovative workplace behavior

Originality/value

The briefing saves busy executives and researchers hours of reading time by selecting only the very best, most pertinent information and presenting it in a condensed and easy-to-digest format.
Research shows offering excellent compensation and job security makes South Korean employees much less likely to quit jobs
Authors: Smith David
Published: July 2021

Purpose

The researcher wanted to study the effect of HRM practices on turnover in a South Korean context. Previous studies have focused on Western contexts.

Design/methodology/approach

The author collected data from 310 white-collar and knowledge workers from Seoul. A set of five hypotheses were tested

Findings

The results showed that offering excellent compensation and job security made employees much less likely to leave. However, the indirect effect of job autonomy was not found to be significant.

Originality/value

The study has theoretical implications for workplaces. First, the findings show compensation satisfaction is of crucial importance and HR retention strategies should focus on how employees perceive their pay, benefits and pay policies. Second, the results show that HR managers and top-level executives should make job security a primary concern. For example, they should provide accurate and honest information” about the causes and actions.
Spherical uncertain linguistic Hamacher aggregation operators and their application on achieving consistent opinion fusion in group decision making
Authors: Qiyas Muhammad , Abdullah Saleem , Naeem Muhammad
Published: July 2021

Purpose

The aim of this research is to establish a new type of aggregation operator based on Hamacher operational law of spherical uncertain linguistic numbers (SULNs).

Design/methodology/approach

First, the authors define spherical uncertain linguistic sets and develop some operational laws of SULNs. Furthermore, the authors extended these operational laws to the aggregation operator and developed spherical uncertain linguistic Hamacher averaging and geometric aggregation operators.

Findings

The authors were limited in achieving a consistent opinion on the fusion in group decision-making problem with the SULN information.

Originality/value

In order to give an application of the introduced operators, the authors first constrict a system of multi-attribute decision-making algorithm.
The challenge of skilled expatriates from the Indian subcontinent losing intellectual capital in Australia: resolving the crisis of habitus
Authors: Mohyuddin Syed , Sengupta Santoshi , Patel Parth , Prikshat Verma , Varma Arup
Published: July 2021

Purpose

This article aims to examine the challenges faced by highly skilled expatriates (i.e. professionals and managers) from the Indian subcontinent (i.e. India and neighboring countries) as they attempt to advance their careers in Australia. Extant literature has revealed significant gaps between policies for skilled migration proposed by governments in developed countries and the response to policies by organizations in those countries. By employing the theories of habitus, disembedding, sensemaking and acculturation as frameworks for analysis, the authors explore and explain how these expatriates settle and integrate into their new lives and careers as they resolve their experience of habitus.

Design/methodology/approach

This study employed phenomenology and narrative research techniques using 21 in-depth, semistructured interviews with expatriate professionals from India, Pakistan, Sri Lanka and Bangladesh to explore and examine their expatriation experiences and their occupational progress in Australia.

Findings

The findings reveal that on migrating to Australia, expatriate professionals are uprooted from their home country habitus and thrust into new conditions that cause them to lose their cultural, economic, intellectual and social capital, which further leads them into a state of “disembeddedness.” These highly skilled expatriates then rely on sensemaking and acculturation to resolve their crisis of habitus. The authors also found that gender is a significant factor in this process, as female expatriates faced more career-related barriers compared to their male counterparts.

Originality/value

This article brings into focus previously unexamined avenues of expatriation research and proposes a novel theoretical framework that is instrumental in explaining the settlement and integration process of highly skilled professionals from emerging nations.
Modelling the priority attributes of customer loyalty in Philippine single-dish restaurants
Authors: Padillo Jr Clotildo , Go Noella , Manreal Pacco , Samson Samuel , Galli Brian , Yamagishi Kafferine , Promentilla Michael Angelo , Ocampo Lanndon
Published: July 2021

Purpose

Despite the growing trend for single-dish restaurants in the Philippines, understanding customer loyalty for this subsector is scarce in the current literature. To address such a gap, this paper aims to identify attributes and their sub-attributes that contribute to customer loyalty for single-dish restaurants.

Design/methodology/approach

Using the analytic hierarchy process, the priorities of these attributes in achieving customer loyalty were generated from a group of expert decision-makers. A representative case study in the Philippines with an emerging market trend for single-dish restaurants was conducted.

Findings

Findings show that “value” is the most crucial attribute in achieving customer loyalty, followed by “food” and “service” attributes, which are straightforward implications of single-dish restaurants. More strikingly, the “atmosphere” attribute ranks last in the priority list, which may mean that customers consider fancy environments with less priority when dining in these types of restaurants. In the priority sub-attributes, “dining experience” and “tastiness” came up on top of the list, with the “music” attribute ranking last. These findings are crucial inputs to inform the design of strategies that would enhance the customer base.

Originality/value

This study reports the first attempt to rigorously analyze single-dish restaurants, which gain little attention in the current literature, yet an emerging type of restaurant, especially in developing economies. With significant differences in many aspects of mainstream restaurants, customer loyalty attributes may be different. This paper determines the list of priority attributes and sub-attributes of customer loyalty for Philippine single-dish restaurants. Identifying these priority attributes contributes to the extant literature by offering valuable insights for relevant decision-makers in gaining competitive advantage within their market niches.
Prioritizing the barriers to tourism growth in rural India: an integrated multi-criteria decision making (MCDM) approach
Authors: Jena R.K. , Dwivedi Yogesh
Published: July 2021

Purpose

Tourism is one of the upcoming service industry in India with high potentials for future growth, particularly in rural areas. Many potential barriers are affecting the growth of tourism in rural India. Therefore, it is essential to explore and prioritize the barriers to tourism growth in rural India.

Design/methodology/approach

Qualitative and quantitative responses from “16” experts related to tourism and hospitality management from central India are collected for this study. An integrated Multi-Criteria Decision Making (MCDM) based framework is adopted to identify and relate significant barriers to tourism growth in India.

Findings

The result of the study identified many significant barriers and their importance to tourism growth in rural India.

Research limitations/implications

The findings of this study add to the knowledge base of tourism research in line with the previous literature. This study offers an in-depth understanding of barriers focusing on rural tourism growth and devising both the plan of action and the suggestive measures in dealing with rural tourism.

Originality/value

The study provides a robust framework by integrating Interpretive Structural Modelling(ISM) and Decision Making Trial and Evaluation Laboratory (DEMATEL) to explore and prioritizing the critical barriers to rural tourism growth in India. The results of this study can help the decision-maker to fundamentally improve the economy of India through the growth of rural tourism.
The political ecology of cocoa in Ghana: Past, present and future challenges
Authors: Bryant Chris , Mitchell Matthew I.
Published: July 2021

In recent years, many have raised concerns regarding the need to develop sustainable practices in the cocoa sector and to prepare for impending threats associated with climate change. Although evidence suggests more needs to be done to address the environmental concerns surrounding cocoa, the sustainability of the sector cannot be understood without recognizing other socio‐economic and socio‐political factors. This paper uses a case study of Ghana—the world's second largest producer of cocoa—to problematize the often‐simplistic claims concerning the fate of the crop. While the paper draws upon a diverse disciplinary body of literature, it uses a political ecology lens to analyse the multifaceted problems facing the cocoa industry. The paper derives insights from 131 interviews conducted with a wide range of stakeholder groups in Ghana's capital (Accra) and leading cocoa‐producing regions (Ashanti and Western). The analysis reveals the need to challenge dominant narratives about the cocoa‐climate change nexus, as it highlights other threats to the sector. This includes the difficulty of securing youth labourers, the problem of “galamsey” (i.e., illegal artisanal mining), the issue of land scarcity, and the politicization of migrant workers.
Building prediction models with grouped data: A case study on the prediction of turnover intention
Authors: Yuan Shuai , Kroon Brigitte , Kramer Astrid
Published: July 2021

The availability of big data spurred the application of modern prediction analytics (e.g., machine learning methods) in human resource management (HRM) research and practice. Due to the novel and technical nature of prediction analytics, HR professionals and researchers may struggle to collaborate with data experts. We offer a comprehensive introduction to the logic and value of prediction methods. Moreover, we highlight the concern of treating grouped data—commonly seen in HRM research yet rarely discussed in building prediction models. We introduce different strategies to deal with grouped data in applying prediction models. The performance of different modelling approaches and prediction models are compared in an empirical data set consisting of 1454 employees from 199 small and medium sized enterprise's. Following a workflow to compare the relative performance of the prediction models, the model with the best prediction accuracy was the random‐effects bagged tree that allows for complex relationships and incorporates random effects. Following the estimates of this model, we identified the five most influential predictors of turnover intention: perceived fairness, leader‐member exchange, career opportunities, pay satisfaction and age. The inductive nature of prediction models is expected to advance theory development and HR analytics for developing effective HRM policies.