bluuebunny/crossref_metadata_2025_split huggingface dataset:
A molecular calcium integrator reveals a striatal cell-type driving aversion
Authors: Kim Christina K. , Sanchez Mateo I. , Hoerbelt Paul , Fenno Lief E. , Malenka Robert C. , Deisseroth Karl , Ting Alice Y. 
Published: November 2020

SUMMARYThe ability to record transient cellular events in the DNA or RNA of cells would enable precise, large-scale analysis, selection, and reprogramming of heterogeneous cell populations. Here we report a molecular technology for stable genetic tagging of cells that exhibit activity-related increases in intracellular calcium concentration (FLiCRE). We used FLiCRE to transcriptionally label activated neural ensembles in the nucleus accumbens of the mouse brain during brief stimulation of aversive inputs. Using single-cell RNA sequencing, we detected FLiCRE transcripts among the endogenous transcriptome, providing simultaneous readout of both cell-type and calcium activation history. We identified a cell-type in the nucleus accumbens activated downstream of long-range excitatory projections. Taking advantage of FLiCRE’s modular design, we expressed an optogenetic channel selectively in this cell-type, and showed that direct recruitment of this otherwise genetically-inaccessible population elicits behavioral aversion. The specificity and minute-resolution of FLiCRE enables molecularly-informed characterization, manipulation, and reprogramming of activated cellular ensembles.
Defective Autophagy inSf1Neurons Perturbs the Metabolic Response to Fasting and Causes Mitochondrial Dysfunction
Authors: Coupé Bérengère , Leloup Corinne , Maillard Julien , Pénicaud Luc , Horvath Tamas L. , Bouret Sebastien G. 
Published: November 2020

AbstractObjectiveThe ventromedial nucleus of the hypothalamus (VMH) is a critical component of the forebrain pathways that regulate energy homeostasis. It also plays an important role in the metabolic response to fasting. However, the mechanisms contributing to these physiological processes remain elusive. Autophagy is an evolutionarily conserved mechanism that maintains cellular homeostasis by turning over cellular components and providing nutrients to the cells during starvation. Here we investigated the importance of the autophagy-related geneAtg7inSf1-expressing neurons of the VMH in control and fasted conditions.MethodsWe generatedSf1-Cre;Atg7loxP/loxPmice and examined their metabolic and cellular response to fasting.ResultsFasting induces autophagy in the VMH, and mice lackingAtg7inSf1-expressing neurons display altered regulation in glucose and leptin homeostasis and impaired energy expenditure regulation in response to fasting. Moreover, loss ofAtg7inSf1neurons causes alterations in the central response to fasting. Furthermore, alterations in mitochondria morphology and activity are observed in mutant mice.ConclusionTogether, these data show that autophagy is nutritionally regulated in VMH neurons and that VMH autophagy participates in the control of energy homeostasis during fasting.
Predicting the animal hosts of coronaviruses from compositional biases of spike protein and whole genome sequences through machine learning
Authors: Brierley Liam , Fowler Anna 
Published: November 2020

AbstractThe COVID-19 pandemic has demonstrated the serious potential for novel zoonotic coronaviruses to emerge and cause major outbreaks. The immediate animal origin of the causative virus, SARS-CoV-2, remains unknown, a notoriously challenging task for emerging disease investigations. Coevolution with hosts leads to specific evolutionary signatures within viral genomes that can inform likely animal origins. We obtained a set of 650 spike protein and 511 whole genome nucleotide sequences from 225 and 187 viruses belonging to the familyCoronaviridae, respectively. We then trained random forest models independently on genome composition biases of spike protein and whole genome sequences, including dinucleotide and codon usage biases in order to predict animal host (of nine possible categories, including human). In hold-one-out cross-validation, predictive accuracy on unseen coronaviruses consistently reached ∼73%, indicating evolutionary signal in spike proteins to be just as informative as whole genome sequences. However, different composition biases were informative in each case. Applying optimised random forest models to classify human sequences of MERS-CoV and SARS-CoV revealed evolutionary signatures consistent with their recognised intermediate hosts (camelids, carnivores), while human sequences of SARS-CoV-2 were predicted as having bat hosts (suborder Yinpterochiroptera), supporting bats as the suspected origins of the current pandemic. In addition to phylogeny, variation in genome composition can act as an informative approach to predict emerging virus traits as soon as sequences are available. More widely, this work demonstrates the potential in combining genetic resources with machine learning algorithms to address long-standing challenges in emerging infectious diseases.
Ivermectin reduces coronavirus infectionin vivo: a mouse experimental model
Authors: Arévalo AP , Pagotto R , Pórfido J , Daghero H , Segovia M , Yamasaki K , Varela B , Hill M , Verdes JM , Duhalde Vega M , Bollati-Fogolín M , Crispo M 
Published: November 2020

AbstractSARS-CoV2 is a single strand RNA virus member of the type 2 coronavirus family, responsible for causing COVID-19 disease in humans. The objective of this study was to test the ivermectin drug in a murine model of coronavirus infection using a type 2 family RNA coronavirus similar to SARS-CoV2, the mouse hepatitis virus (MHV). BALB/cJ female mice were infected with 6,000 PFU of MHV-A59 (Group Infected; n=20) and immediately treated with one single dose of 500 μg/kg of ivermectin (Group Infected + IVM; n=20), or were not infected and treated with PBS (Control group; n=16). Five days after infection/treatment, mice were euthanized to obtain different tissues to check general health status and infection levels. Overall results demonstrated that viral infection induces the typical MHV disease in infected animals, with livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while ivermectin administration showed a better health status with lower viral load (23,192 AU; p<0.05) and few livers with histopathological damage (p<0.05), not showing statistical differences with control mice (P=NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in treated mice compared to infected animals. In conclusion, ivermectin seems to be effective to diminish MHV viral load and disease in mice, being a useful model for further understanding new therapies against coronavirus diseases.
High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer
Authors: Pierce Sarah E. , Granja Jeffrey M. , Greenleaf William J. 
Published: November 2020

AbstractSpear-ATAC is a modified droplet-based single-cell ATAC-seq (scATAC-seq) protocol that enables simultaneous read-out of chromatin accessibility profiles and integrated sgRNA spacer sequences from thousands of individual cells at a time. Spear-ATAC profiling of 104,592 cells representing 414 sgRNA knock-down populations revealed the temporal dynamics of epigenetic responses to regulatory perturbations in cancer cells and the associations between transcription factor binding profiles, demonstrating a high-throughput method for perturbing and evaluating dynamic single-cell epigenetic states.
Transient Maternal IL-6 boosts glutamatergic synapses and disrupts hippocampal connectivity in the offspring
Authors: Mirabella Filippo , Desiato Genni , Mancinelli Sara , Fossati Giuliana , Rasile Marco , Morini Raffaella , Markicevic Marija , Grimm Christina , Amegandjin Clara , Termanini Alberto , Peano Clelia , Kunderfranco Paolo , di Cristo Graziella , Zerbi Valerio , Lodato Simona , Menna Elisabetta , Matteoli Michela , Pozzi Davide 
Published: November 2020

SummaryEarly prenatal inflammatory conditions are thought to represent a risk factor for different neurodevelopmental disorders, with long-term consequences on adult brain connectivity. Here we show that a transient IL-6 elevation, occurring at vulnerable stages of early neurodevelopment, directly impacts brain developmental trajectories through the aberrant enhancement of glutamatergic synapses and overall brain hyper-connectivity. The IL6-mediated boost of excitatory synapse density results from the neuron-autonomous, genomic effect of the transcription factor STAT3 and causally involves the activation of RGS4 gene as a candidate downstream target. The STAT3/RGS4 pathway is also activated in neonatal brains as a consequence of maternal immune activation protocols mimicking a viral infection during pregnancy. By demonstrating that prenatal IL-6 elevations result in aberrant synaptic and brain connectivity through the molecular players identified, we provide a mechanistic framework for the association between prenatal inflammatory events and brain neurodevelopmental disorders.
Genetic and Epigenetic Features of Promoters with Ubiquitous Chromatin Accessibility Support Ubiquitous Transcription of Cell-essential Genes
Authors: Fan Kaili , Moore Jill E. , Zhang Xiao-ou , Weng Zhiping 
Published: November 2020

AbstractGene expression is controlled by regulatory elements with accessible chromatin. Although the majority of regulatory elements are cell type-specific, being in the open chromatin state in only one or a few cell types, approximately 16,000 regions in the human genome and 13,000 regions in the mouse genome are in the open chromatin state in nearly all of the 517 human and 94 mouse cell and tissue types assayed by the ENCODE consortium, respectively. We performed a systematic analysis on the subset of 9,000 human and 8,000 mouse ubiquitously (ubi) open chromatin regions that were also classified as candidate cis-regulatory elements (cCREs) with promoter-like signatures (PLSs) by the ENCODE consortium, which we refer to as ubi-PLSs. We found that these ubi-PLSs had higher levels of CG dinucleotides and corresponded to the genes with ubiquitously high levels of transcriptional activities. Furthermore, the transcription start sites of a vast majority of cell-essential genes are located in ubi-PLSs. ubi-PLSs are enriched in the motifs of ubiquitously expressed transcription factors and preferentially bound by transcriptional cofactors that regulate ubiquitously expressed genes. Finally, ubi-PLSs are highly conserved between human and mouse at the synteny level, but not as conserved at the sequence level, with a high turnover of transcription factor motif sites. Thus, there is a distinct set of roughly 9,000 promoters in the mammalian genome that are actively maintained in the open chromatin state in nearly all cell types to ensure the transcriptional program of cell-essential genes.
IL-12 signaling promotes TET2-mediated DNA demethylation during CD8 T cell effector differentiation
Authors: Zebley Caitlin C. , Abdelsamed Hossam A. , Ghoneim Hazem E. , Alli Shanta , Haydar Dalia , Harris Tarsha , McGargill Maureen A. , Krenciute Giedre , Youngblood Ben 
Published: November 2020

SUMMARYCD8 T cell memory differentiation endows T cells with an ability to rapidly induce effector functions upon pathogen re-encounter. While it is well established that substantial epigenetic remodeling occurs during the effector stage of the immune response, the signaling events that imprint CD8 T cells with these stable epigenetic programs are not well-defined. To gain insight into the signaling determinants of effector-associated epigenetic programming among CD8 T cells, we explored the role of IL-12 in the imprinting of IFNg expression during human CD8 T cell priming. We observed that TCR-mediated stimulation of human naïve CD8 T cells is not sufficient to induce substantial demethylation of the IFNg promotor. However, TCR stimulation in the presence of the inflammatory cytokine, IL-12, resulted in significant and stable demethylation of the IFNg locus that was commensurate with an increase in IFNg expression. We further show that IL-12-associated demethylation of the IFNg locus is coupled to cell division through TET2-dependent passive demethylation in anex vivohuman CAR T cell model system and anin vivoimmunologically competent murine system. Collectively, these data illustrate that IL-12 signaling promotes TET2-mediated effector epigenetic programming in CD8 T cells during the primary immune response and serve as proof of concept that signal 3 cytokines can be used to guide the induction of epigenetically regulated traits among T cells used for adoptive immunotherapies.
Expectations about motion direction affect perception and anticipatory smooth pursuit differently
Authors: Wu Xiuyun , Rothwell Austin C. , Spering Miriam , Montagnini Anna 
Published: November 2020

AbstractSmooth pursuit eye movements and visual motion perception rely on the integration of current sensory signals with past experience. Experience shapes our expectation of current visual events and can drive eye movement responses made in anticipation of a target, such as anticipatory pursuit. Previous research revealed consistent effects of expectation on anticipatory pursuit—eye movements follow the expected target direction or speed—and contrasting effects on motion perception, but most studies considered either eye movement or perceptual responses. The current study directly compared effects of direction expectation on perception and anticipatory pursuit within the same direction discrimination task to investigate whether both types of responses are affected similarly or differently. Observers (n= 10) viewed high-coherence random-dot kinematograms (RDKs) moving rightward and leftward with a probability of 50, 70, or 90% in a given block of trials to build up an expectation of motion direction. They were asked to judge motion direction of interleaved low-coherence RDKs (0-15%). Perceptual judgements were compared to changes in anticipatory pursuit eye movements as a function of probability. Results show that anticipatory pursuit velocity scaled with probability and followed direction expectation (attraction bias), whereas perceptual judgments were biased opposite to direction expectation (repulsion bias). Control experiments suggest that the repulsion bias in perception was not caused by retinal slip induced by anticipatory pursuit, or by motion adaptation. We conclude that direction expectation can be processed differently for perception and anticipatory pursuit.
Robust error-based active disturbance rejection control of a quadrotor
Authors: Lechekhab Taki Eddine , Manojlovic Stojadin , Stankovic Momir , Madonski Rafal , Simic Slobodan 
Published: November 2020

Purpose
The control of a quadrotor unmanned aerial vehicle (UAV) is a challenging problem because of its highly nonlinear dynamics, under-actuated nature and strong cross-couplings. To solve this problem, this paper aims to propose a robust control strategy, based on a concept of active disturbance rejection control (ADRC).

Design/methodology/approach
The altitude/attitude dynamics of a quadrotor is reformulated into the ADRC framework. Three distinct variations of the error-based ADRC algorithms, with different structures of generalized extended state observers (GESO), are derived for the altitude/attitude trajectory-following task. The convergence of the observation part is proved based on the singular perturbation theory. Through a frequency analysis and a quantitative comparison in a simulated environment, each design is shown to have certain advantages and disadvantages in terms of tracking accuracy and robustness. The digital prototypes of the proposed controllers for quadrotor altitude and attitude control channels are designed and validated through real-time hardware-in-the-loop (HIL) co-simulation, with field-programmable gate array (FPGA) hardware.

Findings
The effects of unavailable reference time-derivatives can be estimated by the ESO and rejected through the outer control loop. The higher order ESOs demonstrate better performances, but with reductions of stability margins. Time-domain simulation analysis reveals the benefits of the proposed control structure related to classical control approach. Real-time FPGA-based HIL co-simulations validated the performances of the considered digital controllers in typical quadrotor flight scenarios.

Practical implications
The conducted study forms a set of practical guidelines for end-users for selecting specific ADRC design for quadrotor control depending on the given control objective and work conditions. Furthermore, the paper presents detailed procedure for the design, simulation and validation of the embedded FPGA-based quadrotor control unit.

Originality/value
In light of the currently available literature on error-based ADRC, a comprehensive approach is applied here, which includes the design of error-based ADRC with different GESOs, its frequency-domain and time-domain analyses using different simulation of UAV flight scenarios, as well as its FPGA-based implementation and testing on the real hardware.
The impact of social support on job stress of shift working mothers: a study of casino employees in Macao
Authors: Liu Shuang 
Published: November 2020

PurposeThe purpose of this paper is to provide an exploratory understanding of the impact of social support on job stress of shift working mothers in Macao casinos.Design/methodology/approachA qualitative research method was adopted in this study. A snowball sampling strategy was used to recruit participants, and in-depth semi-structured interviews were conducted on participants from different casinos of six Macao gaming operators.FindingsThe paper found out that emotional and instrumental supports from families and friends are the most important social support for shift working mothers to cope with their job stress in casinos.Research limitations/implicationsA qualitative method may lead to a misinterpretation or ignorance of key information due to the researcher bias. The snowball sampling strategy may lead to a biased sample which may not represent the entire population.Originality/valueThe understanding of what types of social support that shift working mothers appreciate and need the most may provide managerial implications for casino operators for a better support to their female employees.
Optimizing window size by integrating energy and lighting analyses considering occupants’ visual satisfaction
Authors: Montaser Koohsari Ayda , Heidari Shahin 
Published: November 2020

PurposeThe purpose of this paper is to determine the approximate window-to-wall ratio (WWR), window width-to-height ratio (WHR) and sill level for a room in Rasht–Gilan province and to present an optimal window in each of the WWR ranges providing the minimum energy consumption by integrating artificial lighting and thermal analyses, whilst maintaining internal comfort conditions using dynamic evaluation.Design/methodology/approachThe process of modelling has four main steps: 1 – defining the building's features and requirements, 2 – validating input weather file data by on-site measurement, 3 – determining input parameters for the lighting and thermal analysis and 4 – clarifying variable parameters and fitness function for the optimization algorithm. Also, the survey study is performed in a daylit office room, in which 30 employees are employed to answer the questions in three different times of a day. In this process, the impact of daylight on their visual comfort is surveyed in 1,350 different illuminance levels which are manually recorded.FindingsThe range of useful daylight illuminance (UDI) values is determined as 200–1,000 lux. The optimum range of WWRs in the case study is 15%–25%. Also, due to the appropriate window height, electric lighting could be decreased by 40%.Originality/valueThermal and lighting performance in buildings is the relation of facade characteristics to environmental sustainability. Recent studies focussed on optimizing WWR and window characteristics considering thermal comfort and energy analyses. However, architects need freedom for designing façade and making decisions in their first sketches. Thus a guideline for optimum window conditions in each WWR is required. Also, considering occupants' behaviour in practical buildings, the visual comfort investigation is a gap in WWR optimization.
Artificial intelligence in personnel management: the development of APM model
Authors: Chang Kirk 
Published: November 2020

Purpose
Managers have mixed views of how artificial intelligence (AI) affects personnel management (PM). The purpose of this paper is to identify potential knowledge gap and bring new insights to the AI-personnel-management literature.

Design/methodology/approach
Both applicability and theoretical perspectives are adopted to critically discuss the constraint and opportunity of AI in PM. Tables and narrative analysis are used to clarify the role of AI in managerial practices.

Findings
Research findings have helped to develop a new model titled AI in Personnel Management (APM). The APM model unfolds itself in three levels, followed by potential outcome. The three levels comprise “organizational, managerial and individual job levels,” and the outcome comprises “organizational performance, employees’ well-being and staff turnover rate”.

Research limitations/implications
The APM model helps managers to understand the implication of AI in their workplace. With better understanding of AI’s implication, managers are more likely to develop appropriate AI-driven managerial policies, which in turn benefit employees and their organizations. The APM model acts as a reference guide, helping managers to evaluate the AI’s constraint and opportunity in their managerial practices.

Originality/value
The APM model is valuable and informative to the academic researchers, as it has first responded to Malik et al. (2019)’s call (re: the absence of AI and management literature), and, more importantly, it has advanced the knowledge of AI–management relationship, supporting scholars to further understand the role of AI in PM.