bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of pro-depressant and immunomodulatory drugs on biases in decision-making in the rat judgement bias task
Authors: Hales CA , Bartlett JM , Arban R , Hengerer B , Robinson ESJ 
Published: October 2020

AbstractStudies in human and non-human species suggest that decision-making behaviour can be biased by affective state, also termed an affective bias. To study these behaviours in non-human species, judgement bias tasks have been developed. Animals are trained to associate specific cues (tones) with a positive or negative/less positive outcome. Animals are then presented with intermediate ambiguous cues and affective biases quantified by observing whether animals make more optimistic or more pessimistic choices. Here we use a high versus low reward judgement bias task and test whether pharmacologically distinct compounds, which induce negative biases in learning and memory, have similar effects on decision-making: tetrabenazine (0.0-1.0mg/kg), retinoic acid (0.0-10.0mg/kg) and rimonabant (0.0-10.0mg/kg). We also tested immunomodulatory compounds: interferon-α (0-100units/kg), lipopolysaccharide (0.0-10.0μg/kg) and corticosterone (0.0-10.0mg/kg). We observed no specific effects in the judgement bias task with any acute treatment except corticosterone which induced a negative bias. We have previously observed a similar lack of effect with acute but not chronic psychosocial stress and so next tested decision-making behaviour following chronic interferon-alpha. Animals developed a negative bias which was sustained even after treatment was ended. These data suggest that decision-making behaviour in the task is sensitive to chronic but not acute effects of most pro-depressant drugs or immunomodulators, but exogenous administration of acute corticosterone induces pessimistic behaviour. This work supports our hypothesis that biases in decision-making develop over a different temporal scale to those seen with learning and memory which may be relevant in the development and perpetuation of mood disorders.Graphical abstract and textDecision-making bias in rats, measured using a judgement bias task, is not altered by acute treatments with pro-depressant or immunomodulatory drugs, but becomes more negative following chronic treatment. The time course of change in decision-making bias reflects the subjective reporting of changes in depression symptoms in humans treated with these drugs.
Modelling disease transmission from touchscreen user interfaces
Authors: Di Battista Andrew , Nicolaides Christos , Georgiou Orestis 
Published: October 2020

AbstractThe extensive use of touchscreens for all manner of human-computer interactions has made them plausible instruments of touch-mediated disease transmission. To that end, we employ stochastic simulations to model human-fomite interaction with a distinct focus on touchscreen interfaces. The timings and frequency of interactions from within a closed population of infectious and susceptible individuals was modelled using a basic queuing network. Apseudoreproductive number (R) was used to compare outcomes under various parameter conditions. We also expanded the simulation to a specific real-world scenario; namely airport self check-in and baggage drop. Results revealed that the required rate of cleaning/disinfecting of screens to effectively mitigateRcan be inordinately high. This suggests that revised or alternative methods should be considered.
Long-term stability of neuronal ensembles in mouse visual cortex
Authors: Pérez-Ortega Jesús , Alejandre-García Tzitzitlini , Yuste Rafael 
Published: October 2020

AbstractCoactive neuronal ensembles are found in spontaneous and evoked cortical activity and are thought to participate in the internal representation of memories, perceptions, and mental states. In mouse visual cortex, ensembles can be optogenetically imprinted and are causally related to visual percepts, but it is still unknown how stable they are over time. Using two-photon volumetric microscopy, we performed calcium imaging over several weeks of the same neuronal populations in layer 2/3 of visual cortex of awake mice, tracking over time the activity of the same neurons in response to visual stimuli and under spontaneous activity. Only a small number of neurons remained active across days. Analyzing them, we found both stable ensembles, lasting up to 46 days, and transient ones, observed during only one imaging session. The majority of ensembles in visually-evoked activity were stable, whereas in spontaneous activity similar numbers of stable and transient ensembles were found. Among stable ensembles, more than 60 % of neurons still belonged to the same ensemble even after several weeks. These core ensemble cells had stronger functional connectivity than neurons that stopped belonging to the ensemble. Our results demonstrate that spontaneous and evoked neuronal ensembles can last weeks, providing a neuronal mechanism for the long-lasting representation of perceptual states or memories.
Brunner syndrome associated MAOA dysfunction in human dopaminergic neurons results in NMDAR hyperfunction and increased network activity
Authors: Shi Yan , van Rhijn Jon-Ruben , Bormann Maren , Mossink Britt , Frega Monica , Recaioglu Hatice , Hakobjan Marina , Gunnewiek Teun Klein , Schoenmaker Chantal , Palmer Elizabeth , Faivre Laurence , Kittel-Schneider Sarah , Schubert Dirk , Brunner Han , Franke Barbara , Kasri Nael Nadif 
Published: October 2020

AbstractBackgroundMonoamine neurotransmitter abundance affects motor control, emotion, and cognitive function and is regulated by monoamine oxidases. Amongst these, monoamine oxidase A (MAOA) catalyzes the degradation of dopamine, norepinephrine, and serotonin into their inactive metabolites. Loss-of-function mutations in the X-linkedMAOAgene cause Brunner syndrome, which is characterized by various forms of impulsivity, maladaptive externalizing behavior, and mild intellectual disability. Impaired MAOA activity in individuals with Brunner syndrome results in bioamine aberration, but it is currently unknown how this affects neuronal function.MethodsWe generated human induced pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neurons from three individuals with Brunner syndrome carrying different mutations, and used CRISPR/Cas9 mediated homologous recombination to rescue MAOA function. We used these lines to characterize morphological and functional properties of DA neuronal cultures at the single cell and neuronal network levelin vitro.ResultsBrunner syndrome DA neurons showed reduced synaptic density but hyperactive network activity. Intrinsic functional properties and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated synaptic transmission were not affected by MAOA dysfunction. Instead, we show that the neuronal network hyperactivity is mediated by upregulation of theGRIN2AandGRIN2Bsubunits of the N-methyl-D-aspartate receptor (NMDAR), and rescue ofMAOAresults in normalization of NMDAR function as well as restoration of network activity.ConclusionsOur data suggest that MAOA dysfunction in Brunner syndrome increases activity of dopaminergic neurons through upregulation of NMDAR function, which may contribute to Brunner syndrome associated phenotypes.
APOEε3/ε4andAPOEε4/ε4genotypes drive unique gene signatures in the cortex of young mice
Authors: Foley Kate E. , Garceau Dylan T. , Kotredes Kevin P. , Carter Gregory W. , Sasner Michael , Howell Gareth R. 
Published: October 2020

AbstractBackgroundRestrictions on mouse models have significantly impacted research towards understanding the most common genotype contributing to dementia in the human population –APOEε3/ε4. To address this, as part of MODEL-AD, we created new versions of humanizedAPOEε4andAPOEε3mice on a C57BL/6J background that allow for unrestricted distribution and breeding.MethodsTo determine similarities and differences betweenAPOEε3/ε4andAPOEε4/ε4risk genotypes, we analyzed peripheral lipid concentrations as well as performed unbiased transcriptional profiling of the cortex at two and four months of age, comparingAPOEε3/ε4andAPOEε4/ε4to the referenceAPOEε3/ε3. To further compare APOE genotypes, cohorts ofAPOEε3/ε3,APOEε3/ε4, andAPOEε4/ε4mice were exercised by voluntary running from 1 month to 4 months of age.ResultsCholesterol composition was significantly influenced by APOE genotype as early as 2 months, while triglycerides were affected by APOE genotype at 4 months. Importantly, RNA-sequencing of the cortex followed by linear modeling or weighted gene co-expression network analysis (WGCNA) revealed that theAPOEε3/ε4genotype showed unique transcriptomic signatures to that ofAPOEε4/ε4. Functional enrichment of theAPOEε3/ε4, but notAPOEε3/ε4genotype, revealed sulfur and heparin binding as significant terms at 2 months, and extracellular matrix and blood coagulation at 4 months. Further, cell specific contributions of significant genes identified endothelial cells as overrepresented in theAPOEε3/ε4but notAPOEε4/ε4genotype. WGCNA analysis confirmed findings from linear modeling but also predicted that running at a young age affects myelination and gliogenesis across APOE genotypes.ConclusionsIn summary,APOEε3/ε4genotype-specific effects were observed in cortical transcriptional profiles, suggesting therapies aimed at modifying APOE biology to treat dementias may need to be targeted to specificAPOEgenotypes.
Mechanisms of protein kinase C epsilon down-regulation by transforming growth factor-beta in lung cancer cells
Authors: Casado-Medrano Victoria , Baker Martin J. , Cooke Mariana , Kazanietz Marcelo G. 
Published: October 2020

ABSTRACTProtein kinase C epsilon (PKCε), a diacylglycerol (DAG)/phorbol ester-regulated PKC isoform, has been widely linked to oncogenesis and metastasis. PKCε plays important roles in the regulation of motility and invasiveness in non-small cell lung cancer (NSCLC). We previously reported that this kinase becomes prominently down-regulated upon TGF-β-induced epithelial-to-mesenchymal transition (EMT), which leads to prominent phenotypic changes. While the phorbol ester PMA causes down-regulation of PKCα, δ and ε within hours, TGF-β requires at least 4 days to reduce the expression levels of PKCε without affecting the expression of other PKCs, an effect that parallels the acquisition of a mesenchymal phenotype. Despite the prominent transcriptional component involved in EMT, we found that PKCε down-regulation does not involve changes in PKCε mRNA levels and was entirely independent of transcriptional activation of thePRKCEgene. Further mechanistic analysis revealed that the reduction in PKCε expression is dependent on proteasomal and endolysosomal pathways, but independent of autophagy processing mechanisms. Site-directed mutagenesis of Lys312 and Lys321 in PKCε prevented its down-regulation in response to either TGF-β or the phorbol ester PMA. The shift in PKCε isozyme levels depending on cell plasticity underscores relevant functional consequences by modulating the expression of this oncogenic/metastatic kinase and highlights key roles of protein stability mechanisms in the control of PKCε phenotypic outcomes.
Neural basis of opioid-induced respiratory depression and its rescue
Authors: Liu Shijia , Kim Dongil , Oh Tae Gyu , Pao Gerald , Kim Jonghyun , Palmiter Richard D. , Banghart Matthew R. , Lee Kuo-Fen , Evans Ronald M. , Han Sung 
Published: October 2020

AbstractOpioid-induced respiratory depression (OIRD) causes death following an opioid overdose, yet the neurobiological mechanisms of this process are not well understood. Here, we show that neurons within the lateral parabrachial nucleus that express the μ-opioid receptor (PBLOprm1neurons) are involved in OIRD pathogenesis. PBLOprm1neuronal activity is tightly correlated with respiratory rate, and this correlation is abolished following morphine injection. Chemogenetic inactivation of PBLOprm1neurons mimics OIRD in mice, whereas their chemogenetic activation following morphine injection rescues respiratory rhythms to baseline levels. We identified several excitatory G-protein coupled receptors expressed by PBLOprm1neurons and show that agonists for these receptors restore breathing rates in mice experiencing OIRD. Thus, PBLOprm1neurons are critical for OIRD pathogenesis, providing a promising therapeutic target for treating OIRD in patients.
Normalization by distributional resampling of high throughput single-cell RNA-sequencing data
Authors: Brown Jared , Ni Zijian , Mohanty Chitrasen , Bacher Rhonda , Kendziorski Christina 
Published: October 2020

AbstractMotivationNormalization to remove technical or experimental artifacts is critical in the analysis of single-cell RNA-sequencing experiments, even those for which unique molecular identifiers (UMIs) are available. The majority of methods for normalizing single-cell RNA-sequencing data adjust average expression in sequencing depth, but allow the variance and other properties of the gene-specific expression distribution to be non-constant in depth, which often results in reduced power and increased false discoveries in downstream analyses. This problem is exacerbated by the high proportion of zeros present in most datasets.ResultsTo address this, we present Dino, a normalization method based on a flexible negative-binomial mixture model of gene expression. As demonstrated in both simulated and case study datasets, by normalizing the entire gene expression distribution, Dino is robust to shallow sequencing depth, sample heterogeneity, and varying zero proportions, leading to improved performance in downstream analyses in a number of settings.Availability and implementationThe R package, Dino, is available on GitHub athttps://github.com/JBrownBiostat/Dino.Contactbrownj@biostat.wisc.edu,kendzior@biostat.wisc.edu
A phylogenomic perspective on gene tree conflict and character evolution in Caprifoliaceae using target enrichment data, with Zabelioideae recognized as a new subfamily
Authors: Wang Hong-Xin , Morales-Briones Diego F. , Moore Michael J. , Wen Jun , Wang Hua-Feng 
Published: October 2020

AbstractThe use of diverse datasets in phylogenetic studies aiming for understanding evolutionary histories of species can yield conflicting inference. Phylogenetic conflicts observed in animal and plant systems have often been explained by hybridization, incomplete lineage sorting (ILS), or horizontal gene transfer. Here, we employed target enrichment data, species tree and species network approaches to infer the backbone phylogeny of the family Caprifoliaceae, while distinguishing among sources of incongruence. We used 713 nuclear loci and 46 complete plastome sequence data from 43 samples representing 38 species from all major clades to reconstruct the phylogeny of the family using concatenation and coalescence approaches. We found significant nuclear gene tree conflict as well as cytonuclear discordance. Additionally, coalescent simulations and phylogenetic species network analyses suggested putative ancient hybridization among subfamilies of Caprifoliaceae, which seems to be the main source of phylogenetic discordance. Ancestral state reconstruction of six morphological characters revealed some homoplasy for each character examined. By dating the branching events, we inferred the origin of Caprifoliaceae at approximately 66.65 Ma in the late Cretaceous. By integrating evidence from molecular phylogeny, divergence times, and morphology, we herein recognize Zabelioideae as a new subfamily in Caprifoliaceae. This work shows the necessity of using a combination of multiple approaches to identify the sources of gene tree discordance. Our study also highlights the importance of using data from both nuclear and chloroplast genomes to reconstruct deep and shallow phylogenies of plants.
Towards end-to-end disease prediction from raw metagenomic data
Authors: Queyrel Maxence , Prifti Edi , Templier Alexandre , Zucker Jean-Daniel 
Published: October 2020

ABSTRACTAnalysis of the human microbiome using metagenomic sequencing data has demonstrated high ability in discriminating various human diseases. Raw metagenomic sequencing data require multiple complex and computationally heavy bioinformatics steps prior to data analysis. Such data contain millions of short sequences read from the fragmented DNA sequences and are stored as fastq files. Conventional processing pipelines consist in multiple steps including quality control, filtering, alignment of sequences against genomic catalogs (genes, species, taxonomic levels, functional pathways, etc.). These pipelines are complex to use, time consuming and rely on a large number of parameters that often provide variability and impact the estimation of the microbiome elements.Training Deep Neural Networks directly from raw sequencing data is a promising approach to bypass some of the challenges associated with mainstream bioinformatics pipelines. Most of these methods use the concept of word and sentence embeddings that create a meaningful and numerical representation of DNA sequences, while extracting features and reducing the dimensionality of the data. In this paper we present an end-to-end approach that classifies patients into disease groups directly from raw metagenomic reads:metagenome2vec. This approach is composed of four steps (i) generating a vocabulary of k-mers and learning their numerical embeddings; (ii) learning DNA sequence (read) embeddings; (iii) identifying the genome from which the sequence is most likely to come and (iv) training a multiple instance learning classifier which predicts the phenotype based on the vector representation of the raw data. An attention mechanism is applied in the network so that the model can be interpreted, assigning a weight to the influence of the prediction for each genome. Using two public real-life data-sets as well a simulated one, we demonstrated that this original approach reaches high performance, comparable with the state-of-the-art methods applied directly on processed data though mainstream bioinformatics workflows. These results are encouraging for this proof of concept work. We believe that with further dedication, the DNN models have the potential to surpass mainstream bioinformatics workflows in disease classification tasks.
Gene Drives Across Engineered Fitness Valleys: Modeling a Design to Prevent Drive Spillover
Authors: de Haas Frederik J.H. , Otto Sarah P. 
Published: October 2020

1AbstractEngineered gene drive techniques for population replacement and/or suppression have potential for tackling complex challenges, including reducing the spread of diseases and invasive species. Unfortunately, the self-propelled behavior of drives can lead to the spread of transgenic elements beyond the target population, which is concerning. Gene drive systems with a low threshold frequency for invasion, such as homing-based gene drive systems, require initially few transgenic individuals to spread and are therefore easy to implement. However their ease of spread presents a double-edged sword; their low threshold makes these drives much more susceptible to spread outside of the target population (spillover). We model a proposed drive system that transitions in time from a low threshold drive system (homing-based gene drive) to a high threshold drive system (underdominance) using daisy chain technology. This combination leads to a spatially restricted drive strategy, while maintaining an attainable release threshold. We develop and analyze a discrete-time model as proof of concept and find that this technique effectively generates stable local population suppression, while preventing the spread of transgenic elements beyond the target population under biologically realistic parameters.
Segmentation of wine consumers based on level of involvement: a case of Lebanon
Authors: Koksal Mehmet Haluk 
Published: October 2020

PurposeThe purpose of this study is to segment Lebanese wine customers based on their level of involvement with wine. It also profiles them on the basis of wine drinking motivations, wine attributes and information sources, wine consumption and purchasing behaviour and socio-demographic characteristics.Design/methodology/approachThe data in the study was collected from the main supermarkets, hypermarkets and special liquor outlets as well as upscale restaurants serving alcohol in the Lebanese capital, Beirut, through a structured questionnaire. Out of 700 people approached, only 498 surveys were collected. After splitting consumers into three different segments: high, moderate and low involvement, the study clearly profiles the groups by employing principal component analysis, ANOVA and chi-square analysis.FindingsAfter splitting consumers into three different groups based on involvement with wine; high, moderate and low, the study clearly identified the differences between groups regarding wine attributes, information sources, purchasing and consumption and socio-demographic characteristics.Originality/valueAlthough there are plenty of studies on the examination of wine consumers in the literature from diverse countries, this is the first study investigating wine consumers based on wine involvement in a Middle Eastern country, Lebanon.
Workplace incivility: the impact on the Malaysian public service department
Authors: Alias Mazni , Ojo Adedapo Oluwaseyi , Ameruddin Nur Farhana Lyana 
Published: October 2020

Purpose
This study aims to investigate the implication of workplace incivility among employees in the public service department in Putrajaya involving job satisfaction, work stress, psychological contract, knowledge sharing and work engagement.

Design/methodology/approach
This cross-sectional study examines the implication of workplace incivility among 180 employees in the Malaysian public service organization. Purposive sampling was used in this study. Partial least square was used to examine the measurement and the structural model of this study.

Findings
The result demonstrated that workplace incivility was associated with the psychological contract, job satisfaction, work stress and work engagement. The study also found that workplace incivility does not impact knowledge sharing in the public service organization department.

Practical implications
Future research could provide a more broadened scope to ensure the generalization of the results for the overall public service in Malaysia. Human resource development researchers could look into experimental studies to raise the awareness of workplace incivility that may lead to the decline of workplace incivility.

Originality/value
The research could trigger more empirical research toward understanding the phenomenon and implication of workplace incivility in the perspective of Malaysian public service organizations specifically in Asian countries, which are currently limited.