bluuebunny/crossref_metadata_2025_split huggingface dataset:
Staphylococcus aureussecretes immunomodulatory RNA and DNA via membrane vesicles
Authors: Rodriguez Blanca V. , Kuehn Meta J. 
Published: September 2020

AbstractBacterial-derived RNA and DNA can function as ligands for intracellular receptor activation and induce downstream signaling to modulate the host response to bacterial infection. The mechanisms underlying the secretion of immunomodulatory RNA and DNA by pathogens such asStaphylococcus aureusand their delivery to intracellular host cell receptors are not well understood. Recently, extracellular membrane vesicle (MV) production has been proposed as a general secretion mechanism that could facilitate the delivery of functional bacterial nucleic acids into host cells.S. aureusproduce membrane-bound, spherical, nano-sized, MVs packaged with a select array of bioactive macromolecules and they have been shown to play important roles in bacterial virulence and in immune modulation through the transmission of biologic signals to host cells. Here we show thatS. aureussecretes RNA and DNA molecules that are mostly protected from degradation by their association with MVs. Importantly, we demonstrate that MVs can be delivered into cultured macrophage cells and subsequently stimulate a potent IFN-β response in recipient cells via activation of endosomal Toll-like receptors. These findings advance our understanding of the mechanisms by which bacterial nucleic acids traffic extracellularly to trigger the modulation of host immune responses.
Multimodal single-cell/nucleus RNA-sequencing data analysis uncovers molecular networks between disease-associated microglia and astrocytes with implications for drug repurposing in Alzheimer’s disease
Authors: Xu Jielin , Zhang Pengyue , Huang Yin , Bekris Lynn , Lathia Justin , Chiang Chien-Wei , Li Lang , Pieper Andrew A. , Leverenz James B. , Cummings Jeffrey , Cheng Feixiong 
Published: September 2020

AbstractSystematic identification of molecular networks in disease relevant immune cells of the nervous system is critical for elucidating the underlying pathophysiology of Alzheimer’s disease (AD). Two key immune cell types, disease-associated microglia (DAM) and disease-associated astrocytes (DAA), are biologically involved in AD pathobiology. Therefore, uncovering molecular determinants of DAM and DAA will enhance our understanding of AD biology, potentially identifying novel therapeutic targets for AD treatment. Here, we present an integrative, network-based methodology to uncover conserved molecular networks between DAM and DAA. Specifically, we leverage single-cell and single-nucleus RNA sequencing data from both AD transgenic mouse models and AD patient brains, drug-target networks, metabolite-enzyme associations, and the human protein-protein interactome, along with large-scale patient data validation from the MarketScan Medicare Supplemental Database. We find that common and unique molecular network regulators between DAM (i.e,PAK1, MAPK14, andSYK) and DAA (i.e.,NFKB1, FOS, andJUN) are significantly enriched by multiple neuro-inflammatory pathways and well-known genetic variants (i.e.,BIN1) from genome-wide association studies. Further network analysis reveal shared immune pathways between DAM and DAA, including Fc gamma R-mediated phagocytosis, Th17 cell differentiation, and chemokine signaling. Furthermore, integrative metabolite-enzyme network analyses imply that fatty acids (i.e., elaidic acid) and amino acids (i.e., glutamate, serine, and phenylalanine) may trigger molecular alterations between DAM and DAA. Finally, we prioritize repurposed drug candidates for potential treatment of AD by agents that specifically reverse dysregulated gene expression of DAM or DAA, including an antithrombotic anticoagulant triflusal, a beta2-adrenergic receptor agonist salbutamol, and the steroid medications (fluticasone and mometasone). Individuals taking fluticasone (an approved anti-inflammatory and inhaled corticosteroid) displayed a significantly decreased incidence of AD (hazard ratio (HR) = 0.858, 95% confidence interval [CI] 0.829-0.888,P< 0.0001) in retrospective case-control validation. Furthermore, propensity score matching cohort studies also confirmed an association of mometasone with reduced incidence of AD in comparison to fluticasone (HR =0.921, 95% CI 0.862-0.984,P< 0.0001).
Induction of GLUTAMINE DUMPER1reveals a link between amino acid export, abscisic acid, and immune responses
Authors: Yu Shi , Aghamirzaie Delasa , Harich Kim , Collakova Eva , Grene Ruth , Pilot Guillaume 
Published: September 2020

ABSTRACTAmino acid homeostasis in plants is finely tuned to match developmental needs and response to adverse environments. Over-expression of the single-transmembrane domain protein GLUTAMINE DUMPER1 (GDU1) leads to increased amino acid export, reduced growth and constitutive induction of immune responses. We used an inducible gene expression system to tease apart the primary and secondary effects caused byGDU1, and demonstrated that the primary effect is increasing amino acid export, followed by increased amino acid content and abscisic acid (ABA) response, and a subsequent activation of defense responses. TheGDU1-mediated hypersensitivity to ABA partially depended on the E3 ubiquitin ligase LOSS-OF-GDU1 2 (LOG2), a known GDU1 interactor. More importantly, the lysine catabolite pipecolic acid played a pivotal role in theGDU1-induced defense responses. This work unravels a novel relationship between amino acid transport, ABA and defense responses, potentially mediated by the GDU1-LOG2 complex, critical for understanding how plants respond to amino acid imbalance.ONE SENTENCE SUMMARYGenetically induced disturbance of amino acid homeostasis sequentially triggers responses to abiotic stresses and plant defenses to pathogens in Arabidopsis through undefined sensing mechanisms
Dynamic Analysis of Alternative Polyadenylation from Single-Cell RNA-Seq (scDaPars) Reveals Cell Subpopulations Invisible to Gene Expression Analysis
Authors: Gao Yipeng , Li Lei , Amos Christopher I. , Li Wei 
Published: September 2020

AbstractAlternative polyadenylation (APA) is a major mechanism of post-transcriptional regulation in various cellular processes including cell proliferation and differentiation, but the APA heterogeneity among single cells remains largely unknown. Single-cell RNA sequencing (scRNA-seq) has been extensively used to define cell subpopulations at the transcription level. Yet, most scRNA-seq data have not been analyzed in an “APA-aware” manner. Here, we introduce scDaPars, a bioinformatics algorithm to accurately quantify APA events at both single-cell and single-gene resolution using standard scRNA-seq data. Validations in both real and simulated data indicate that scDaPars can robustly recover missing APA events caused by the low amounts of mRNA sequenced in single cells. When applied to cancer and human endoderm differentiation data, scDaPars not only revealed cell-type-specific APA regulation but also identified cell subpopulations that are otherwise invisible to conventional gene expression analysis. Thus, scDaPars will enable us to understand cellular heterogeneity at the post-transcriptional APA level.
Ancestry Inference Using Reference Labeled Clusters of Haplotypes
Authors: Wang Yong , Song Shiya , Schraiber Joshua G. , Sedghifar Alisa , Byrnes Jake K. , Turissini David A. , Hong Eurie L. , Ball Catherine A. , Noto Keith 
Published: September 2020

AbstractWe present ARCHes, a fast and accurate haplotype-based approach for inferring an individual’s ancestry composition. Our approach works by modeling haplotype diversity from a large, admixed cohort of hundreds of thousands, then annotating those models with population information from reference panels of known ancestry. The running time of ARCHes does not depend on the size of a reference panel because training and testing are separate processes, and the inferred population-annotated haplotype models can be written to disk and reused to label large test sets in parallel (in our experiments, it averages less than one minute to assign ancestry from 32 populations to 1,001 sections of a genotype using 10 CPU). We test ARCHes on public data from the 1,000 Genomes Project and HGDP as well as simulated examples of known admixture. Our results demonstrate that ARCHes outperforms RFMix at correctly assigning both global and local ancestry at finer population scales regardless of the amount of population admixture.Author SummaryHuman DNA is inherited from ancestors that come from different populations across the globe and across time. Being able to identify which of those populations make up an individual’s DNA, how much they contribute, and on which chromosomes, is currently an important open research problem with many applications in the study of human diversity and history. As DNA sequencing and genotyping technology has developed, we have greater and greater amounts of data, which allows for the development of new sophisticated machine learning methods to approach this problem, and presents a need to process large amounts of data efficiently. These methods learn from examples of DNA data from known populations, and must be robust to differences in size and diversity among those reference populations. We present a new approach to this problem called ARCHes (Ancestry inference usingReference labeledClusters ofHaplotypes), that models the global diversity of small segments of human DNA sequence (“haplotypes”), and the extent to which these haplotypes are associated with each of a set of population reference panels. It then computes the most likely population assignments and the points along the genome where the populations change. Our experiments show that ARCHes has superior accuracy compared to a state-of-the-art method in identifying source populations and their locations on the genome, regardless of the number of different populations present in the genome, how closely related those populations are. ARCHes is also able to model populations despite having a small amount of population reference DNA data.
Challenges for work–life balance during COVID-19 induced nationwide lockdown: exploring gender difference in emotional exhaustion in the Indian setting
Authors: Bhumika Bhumika 
Published: September 2020

PurposeThis paper aims to attempt to explore the nature of relationship between work–life balance and emotional exhaustion experienced by the employed individuals while working from home during the pandemic COVID-19 induced nationwide lockdown in the Indian setting.Design/methodology/approachData were collected from 180 working professionals in North India who were working from home during the lockdown. PROCESS macro developed for SPSS was used to test the hypotheses.FindingsFindings depicted that in comparison to men, women felt more emotional exhaustion due to personal life interference in work during work from home period. Surprisingly, the relationship between work interference with personal life, and emotional exhaustion did not differ by gender. It was found that the participative leadership could contribute to reduction of work interference with personal life, and through such an influence, emotional exhaustion experienced by an employee could be reduced to some extent.Originality/valueMany previous studies have explored the nature of the relationship between work–life balance and emotional exhaustion, but rarely any study could cover any Pandemic affected working scenario. This study attempted to investigate such a relationship when employees were obligated to mandatorily work from home during the countrywide lockdown.
“Gendering” contamination: physical, social and moral taint in the context of COVID-19
Authors: Simpson Ruth , Morgan Rachel 
Published: September 2020

Purpose
The purpose of this paper is to explore the “gendering” of contamination in the context of COVID-19 where “gendering” is taken to include other, cross-cutting areas of disadvantage.

Design/methodology/approach
This paper draws on secondary sources to explore gender and COVID-19.

Findings
The authors show that contamination is rooted in structural disadvantage, reproducing classed, gendered and racial difference in terms of how it is encountered and experienced.

Practical implications
This “thought piece” suggests a greater awareness of how pandemics and other public health emergencies impact of structural disadvantages.

Originality/value
This “thought piece” applies notions of taint to a contemporary pandemic that has had far-reaching consequences for issues of equality.
Teaching leadership the “Day After”, with care
Authors: Panayiotou Alexia 
Published: September 2020

Purpose
This paper aims to share the author’s thoughts and reflections on teaching leadership in “pandemic times”. The author has been teaching leadership for nearly 20 years, both to undergraduate and graduate students, always stressing the importance of humility and compassion, traits that were often doubted and questioned vis-à-vis more traditional, masculine, perceptions of leadership. Yet, local and international leadership during the pandemic brought to surface the need and effectiveness of such characteristics, or what the author calls “the need for a feminist ethics of care” in leadership.

Design/methodology/approach
This paper is a thought piece stemming from the author’s experiences and reflections.

Findings
The paper discusses the fact that the most successful handling of the pandemic was largely carried out by female leaders, while also asking “why did so many male leaders do badly?”

Research limitations/implications
With this thought piece, the author hopes to not only engage the readers in a discussion about effective leadership but also on how to teach leadership in today’s schools of management.

Originality/value
The paper hopes to serve as a springboard for opening the discussion around traditional masculinist modes of leadership that have proven to be detrimental in managing the COVID-19 pandemic while also proposing that feminist leadership embedded in an ethics of care is what the world needs today.
Uplift behaviour of axial granular pile anchor encased with geogrid in cohesionless soil
Authors: Sharma Abhishek , Sharma Ravi Kumar 
Published: September 2020

PurposeThe purpose of this paper is to provide a cost-effective foundation technique for the design of foundations of transmission towers, heavily loaded structures, etc.Design/methodology/approachExperimental model tests are conducted in a model test tank to find out the effect of length and diameter of geogrid encased granular pile anchors, the relative density of sand and the angle of inclination of the pile from the vertical on uplift behavior of granular pile anchors.FindingsThe uplift capacity of the geogrid encased granular pile anchor increased with increasing length and diameter of granular pile anchor. Further, increasing the relative density of surrounding soil increased uplift capacity of geogrid encased granular pile anchor system. Moreover, increasing the angle of inclination of loading also increased uplift capacity of whole system. Thus, the proposed system can be effectively used in field for further applications.Originality/valueThe paper is helpful for the engineers looking for cost-effective foundation techniques for heavily loaded structures.
Reducing nonpriority queues at theme parks
Authors: Sakamoto Noriaki 
Published: September 2020

PurposeThis study examined the waiting times to board an attraction at a theme park (Tokyo DisneySea in Japan) using a simulation based on measured values. Park visitors often complain that waiting times are too long; guests (Disney's term for park visitors) must stand in long, slow-moving queues outdoors in all weather, enduring heat, cold, rain and wind. This can undermine their health and reduce customer satisfaction. To date, no research has offered a scientific approach to solve the problem in the context of theme park queues.Design/methodology/approachThe attraction examined two queues: a short waiting queue for guests with priority entry tickets and a long waiting queue for guests without priority entry tickets. The total number of guests with priority entry tickets remained a constant value, as in the current system; however, the author designed the number as a monotonically increasing function to reduce the waiting times for nonpriority entry. It was impractical to analyze queues or try to explain proposed wait time reduction methods using theories and mathematical models alone. Therefore, the author used a simulation study based on real data to demonstrate the proposed method of this study.FindingsThe simulation results indicated that the proposed method significantly decreased guests' waiting times in the nonpriority entry queue, without changing the number of guests in both priority and nonpriority entry queues.Research limitations/implicationsSimple queues can be analyzed using theoretical calculations, but complicated queue systems require simulation methods. Therefore, this paper cannot provide a theoretical basis for the method.Practical implicationsThe proposed method offers benefits to managers of any event or location seeking to manage queue times and not just theme parks (e.g. exhibitions, concerts, etc.). Advance tickets are equivalent to priority entry tickets, so applying the proposed method can shorten waiting times on the day of the event.Originality/valueThis study has important practical implications for queues management, and the proposed approach is a unique system that reduces waiting times, thus increasing customer satisfaction. The proposed method can be applied to similar types of priority entry systems.
Does open access to academic research help small, science-based companies?
Authors: ElSabry ElHassan , Sumikura Koichi 
Published: September 2020

PurposeThis study investigates the extent to which a company's usage of open access (OA) literature for R&D activities depends on its size. The authors’ assumption is that smaller pharmaceutical companies have less access to (usually expensive) journal subscriptions.Design/methodology/approachA fixed-effect Poisson model was used to study a panel dataset of USPTO pharmaceutical company patents. The dependent variable is the count of citations to OA resources in a given company patent.FindingsResults support current anecdotal evidence that many SMEs suffer from high journal prices.Originality/valueThis result justifies the assumption made by policymakers about the potentially positive impact OA mandates have on national innovation activity. It was also shown that collaborating with universities can be a potential coping mechanism for companies that struggle to gain access to the journals they need. In addition to the novelty of its findings, this study introduces a new way to study the impact of OA in nonacademic contexts.
An instructional note to obtain an efficient portfolio with a short sale restriction
Authors: Thompson Thomas H. 
Published: September 2020

PurposeThe purpose of this paper is to provide a SAS program for an efficient portfolio given a short sale restriction.Design/methodology/approachWe provide a 50-stock portfolio given 50 weekly stock returns. We contrast results with a 50-stock portfolio without a restriction.FindingsWe portfolio weights and utility scores for a range of returns from zero to 2.06%.Practical implicationsThis program can be used for any sized portfolio.Originality/valueThis is the first SAS program for a 50-stock portfolio given return information.
Influence of social capital offline and online on early-stage entrepreneurs
Authors: Silva Tatiane Andreza de Souza , Corrêa Victor Silva , Vale Gláucia Maria Vasconcellos , Giglio Ernesto Michelangelo 
Published: September 2020

PurposeThe purpose of this article is to investigate if and how social capital offline – stemming from face-to-face interactions – and social capital online – stemming from social digital media – can influence early-stage entrepreneurs, i.e. ventures with up to 42 months of existence.Design/methodology/approachThe authors used herein a qualitative research approach. The method used was the case study. The authors investigated three early-stage entrepreneurs in order to achieve the objective of the paper. These entrepreneurs are both the unit of analysis and the unit of observation.FindingsThe outcomes of this research indicate (1) the combined importance of social capital offline and online; (2) the different performance of the two different types of social capital (they seem to operate in relatively distinct ways) and (3) the existence of recursiveness between resources stemming from the two social spheres (offline and online).Research limitations/implicationsAs research limitations, the authors point out the following: (1) the use of semistructured interviews as the only data collection instrument; (2) the limitation of the outcomes to entrepreneurs only (3) the absence of information on the performance of the business ventures; the focus of the paper was only on establishing causality between social capital offline and online and entrepreneurial performance.Originality/valueThis paper provides important research contributions. Initially, the paper presents a range of offline and online variables, which can be used in further research. At the same time, the paper emphasizes the combined impact of social capital offline and online, expanding the literature related to entrepreneurship. Moreover, this study proposes the creation of an integrative model. Finally, the authors point out the need for new theoretical and empirical studies on the subject, which still presents a gap in the literature.
The real body of therapeutic communities in society of lockdown
Authors: Bruschetta Simone 
Published: September 2020

Purpose
It is argued that COVID-19 epidemic has critically affected, from many points of view, the hyper-modern economic system, dominant in the globalized capitalist societies. This paper aims to describe the point of view of therapeutic communities, basing my reflections on the Italian experience.

Design/methodology/approach
The author would like to share a critical thought on three issues that this pandemic crisis has made manifest in Italian society: the return of the removed bodies, the feeling of excess represented by therapeutic communities and the emergence of the need for a common thought.

Findings
Body become again an object of studies and with it also the group, as grouping of the bodies. Also the community become a now old-object of studies, as grouping of bodies and groups in a human environment. The objectives of this study are presented as the substance of the democratic vision of society, which therapeutic communities have a responsibility to promote scientifically and ethically.

Originality/value
Therapeutic community is presented as transformative and evolutionary for individuals and groups that compose it, as equally conflictual and destructive, both internally and externally. The author thinks this is the substance of the democratic vision of society, which therapeutic communities have a responsibility to promote scientifically and ethically.