bluuebunny/crossref_metadata_2025_split huggingface dataset:
The retinoic acid receptor drives neuroinflammation and fine tunes the homeostasis of interleukin-17-producing T cells
Authors: Agerholm Rasmus , Rizk John , Kadekar Darshana , Borch Annie , Hadrup Sine Reker , Bekiaris Vasileios 
Published: August 2020

AbstractThe vitamin A metabolite retinoic acid (RA) and its receptor (RAR) are one of the key interactions regulating cellular immunity and neural signaling. Whether endogenous RA-RAR interactions contribute to the development of neuroinflammation and diseases like multiple sclerosis, remains to be elucidated. Herein, we used the murine experimental autoimmune encephalomyelitis (EAE) model and an established genetic RAR silencing approach to decipher its role in pathogenic T cell responses. We show that RAR is necessary for the development of interleukin(IL)-17-driven, cell-mediated immunopathology in the brain and that it fine tunes the homeostasis of IL-17-producing gamma delta (γδT17) and CD4+T cells (TH17). At steady-state, RAR was required in the γδT17 compartment to sustain optimal cell numbers and maintain expression of genes involved in cell cycle progression. In contrast, RAR negatively regulated T helper-17 (TH17) cell homeostasis. Our data show that RAR is required during the early phases of EAE in order to induce a γδT17 response and that its activity is necessary throughout the course of the disease to allow TH17 and γδT17 cells to infiltrate the brain. This is correlated with failure of RAR deficient cells to express surface integrin-alpha4, a major brain homing molecule. Collectively, our work demonstrates that endogenous RA-RAR interactions are important for the homeostasis of IL-17-producing T cells and necessary for their pathogenicity during neuroinflammation.One sentence summaryRetinoic acid receptor activity was required on IL-17-producing CD4+and γδ T cells to induce their neuropathogenicity, and to regulate both positively and negatively their homeostasis.
UPRmtscales mitochondrial network expansion with protein synthesis via mitochondrial import
Authors: Shpilka Tomer , Du YunGuang , Yang Qiyun , Melber Andrew , Naresh Nandhitha U. , Lavelle Joshua , Liu Pengpeng , Weidberg Hilla , Li Rui , Yu Jun , Zhu Lihua Julie , Strittmatter Lara , Haynes Cole M. 
Published: August 2020

AbstractAs organisms develop, individual cells generate mitochondria to fulfill physiologic requirements. However, it remains unknown how mitochondrial network expansion is scaled to cell growth and impacted by environmental cues. The mitochondrial unfolded protein response (UPRmt) is a signaling pathway mediated by the transcription factor ATFS-1 which harbors a mitochondrial targeting sequence (MTS)1. Here, we demonstrate that ATFS-1 mediates an adaptable mitochondrial expansion program that is active throughout normal development. Developmental mitochondrial network expansion required the relatively inefficient MTS2in ATFS-1, which allowed the transcription factor to be responsive to parameters that impact protein import capacity of the entire mitochondrial network. Increasing the strength of the ATFS-1 MTS impaired UPRmtactivity throughout development due to increased accumulation within mitochondria. The insulin-like signaling-TORC13and AMPK pathways affected UPRmtactivation4,5in a manner that correlated with protein synthesis. Manipulation to increase protein synthesis caused UPRmtactivation. Alternatively, S6 kinase inhibition had the opposite effect due to increased mitochondrial accumulation of ATFS-1. However, ATFS-1 with a dysfunctional MTS6constitutively increased UPRmtactivity independent of TORC1 function. Lastly, expression of a single protein with a strong MTS, was sufficient to expand the muscle cell mitochondrial network in an ATFS-1-dependent manner. We propose that mitochondrial network expansion during development is an emergent property of the synthesis of highly expressed mitochondrial proteins that exclude ATFS-1 from mitochondrial import, causing UPRmtactivation. Mitochondrial network expansion is attenuated once ATFS-1 can be imported.
Mutations of SARS-CoV-2 nsp14 exhibit strong association with increased genome-wide mutation load
Authors: Eskier Doğa , Suner Aslı , Oktay Yavuz , Karakülah Gökhan 
Published: August 2020

AbstractSARS-CoV-2 is a betacoronavirus responsible for human cases of COVID-19, a pandemic with global impact that first emerged in late 2019. Since then, the viral genome has shown considerable variance as the disease spread across the world, in part due to the zoonotic origins of the virus and the human host adaptation process. As a virus with an RNA genome that codes for its own genomic replication proteins, mutations in these proteins can significantly impact the variance rate of the genome, affecting both the survival and infection rate of the virus, and attempts at combating the disease. In this study, we analyzed the mutation densities of viral isolates carrying frequently observed mutations for four proteins in the RNA synthesis complex over time in comparison to wildtype isolates. Our observations suggest mutations in nsp14, an error-correcting exonuclease protein, have the strongest association with increased mutation load in both regions without selective pressure and across the genome, compared to nsp7, 8, and 12, which form the core polymerase complex. We propose nsp14 as a priority research target for understanding genomic variance rate in SARS-CoV-2 isolates, and nsp14 mutations as potential predictors for high mutability strains.
The Nutrient and Energy Pathway Requirements for Surface Motility of Nonpathogenic and UropathogenicEscherichia coli
Authors: Sudarshan Sushmita , Hogins Jacob , Ambagaspitiye Sankalya , Zimmern Philippe , Reitzer Larry 
Published: August 2020

ABSTRACTUropathogenicE. coli(UPEC) is the causative pathogen for most uncomplicated urinary tract infections. Flagellar-mediated motility is essential for virulence and colonization for ascending urinary tract infections. The appendage requirement for surface motility depends on the strain: nonpathogenicE. coli(NPEC) lab strains use pili, NPEC hypermotile derivatives use flagella, and UPEC strains use flagella.E. coliflagella-dependent surface motility had been previously shown to require glucose and amino acids. We examined the nutritional and pathway requirements of the NPEC strain W3110 for pili-dependent surface motility, which have not been previously examined. We then compared these requirements to those for two strains with flagella-dependent surface motility: a variant of W3110, W3110-J1, in which the synthesis of the activator of flagella synthesis has been upregulated and the UPEC strain UTI89. The glucose requirement for W3110 was higher than that for either W3110-J1 or UTI89. The pathways required for motility were also different. W3110, but not UTI89, required the Embden-Meyerhof-Parnas pathway via PfkA; conversely, UTI89, but not W3110, required the Entner-Doudoroff pathway, acetogenesis, and the TCA cycle. Glucose did not control flagella synthesis for W3110-J1 and UTI89. The differing requirements for surface motility are likely to reflect major metabolic differences between strains. The metabolic requirements for UTI89 motility suggest a specific adaptation to the urinary tract environment.IMPORTANCEUrinary tract infections affect over 50% of women andE. coliis the most common uropathogen. Virulence requires both pili and flagella, and both appendages can contribute to surface motility. Previous studies ofE. colisurface motility did not consider the appendage requirement and the ability to switch the surface appendage. The nutrient and pathway requirements for surface motility of a non-pathogenicE. colistrain with either pili- or flagella-dependent surface motility and the uropathogen UTI89 were examined. Pili-dependent surface motility required glycolysis, while flagella-dependent motility required the TCA cycle and oxidative phosphorylation and was less dependent on glycolysis. The distinctive nutrient and pathway requirements for UTI89 motility probably result from metabolic adaptations to the urinary tract.
Response of mycorrhizae to herbivory and soil moisture in a semiarid grazing ecosystem
Authors: Tiruvaimozhi Yadugiri V , Bagchi Sumanta , Sankaran Mahesh 
Published: August 2020

AbstractArbuscular mycorrhizal fungal (AMF) symbioses with plants can be influenced by top-down forces such as grazing, and also by bottom-up forces such as soil resource availability, both of which are being altered by anthropogenic and global change drivers. While the influence of each of these factors on AMF symbioses has been widely studied, explicit tests of the relative strengths of top-down versus bottom-up influences on these ubiquitous plant root symbioses are few. We studied AMF colonization responses of four species of graminoids (3 grassesElymus longae-aristatus,Leymus secalinusandStipa orientalis, and a sedgeCarex melanantha) common to semiarid high-altitude rangelands of the Spiti region, Trans-Himalaya, to changes in a top-down driver, grazing intensity (through short-term clipping and long-term grazer exclusion experiments), and a bottom-up driver, water availability (using irrigation treatments, and by evaluating responses to annual precipitation levels across years). Over three years, AMF colonization in all four host species was influenced by precipitation, with the highest and lowest AMF colonization levels corresponding to years with the lowest and highest rainfall, respectively. However, responses to long-term grazer exclusion differed among host species, and across years: while some species showed decreases in AMF colonization levels under grazing, others showed increases from ungrazed control levels, and these responses changed, even reversed, across years. Responses to short-term clipping and irrigation treatments also differed among hosts, with some species responding to irrigation alone, some to clipping and irrigation combined, and others showing no changes in AMF colonization from control levels in any of the treatments. In our study, long-term changes in water availability influenced AMF colonization levels, while short-term responses were host specific. Responses to above-ground tissue loss, however, differed among host species both in the long- and short-term. Overall, this study demonstrates that while AMF colonization levels correspond to annual precipitation levels in this semiarid ecosystem, host species also play a role in influencing plant-AMF interactions in these rangelands, with colonization levels and responses to abiotic factors changing with host species.
New models to study plasma cells in mouse based on the restriction of IgJ expression to antibody secreting cells
Authors: Ayala Maria Victoria , Bonaud Amélie , Bender Sébastien , Lambert Jean-Marie , Lechouane Fabien , Carrion Claire , Cogné Michel , Pascal Virginie , Sirac Christophe 
Published: August 2020

ABSTRACTPlasma cells (PC) represent the last stage of B cell development and are mainly characterized by their capacity of secreting large quantities of antibodies. They can be implicated in a broad-spectrum of neoplastic disorders, including Multiple Myeloma, Waldenstrom macroglobulinemia or Monoclonal Gammopathy of Clinical Significance, all characterized by the abnormal proliferation of a PC clone. Up to date, there are only few reporter models to specifically follow PC development, migration and homing in mouse and none allowing the genetic manipulation of these cells. We created a transgenic mouse model in which a green fluorescent protein gene was placed under the control of the well-characterized regulatory elements of the murine immunoglobulin J (IgJ) chain locus. Thanks to this model, we demostrated that IgJ is an early and specific marker of antibody secreting cells (ASCs) and appears before the expression of CD138, making it a good candidate to targeted genetic modifications of plasma cells. Therefore, a conditional deletion model using a Tamoxifen-dependent Cre recombinase inserted into the IgJ locus was characterized. Using a reporter model, we showed that, in contrast with existing models of B cell lineage genetic modification, the activity of the CRE recombinase only affects ASCs after tamoxifen treatment. Additionally, we used this model in a functionalin vitroassay, to show that Ig modifications directly affect plasma cell survival. These two new mouse models, IgJGFPand IgJCreERT2represent exquisite tools to study PCs. In pathology, the IgJCreERT2model opens new frontiers forin vivogenetic modifications of PCs to better reflect the pathophysiology of PC-related diseases.
ATF3 drives senescence by reconstructing accessible chromatin profiles
Authors: Zhang Chao , Zhang Xuebin , Guan Yiting , Huang Xiaoke , Zhang Lijun , Tian Xiao-Li , Tao Wei 
Published: August 2020

AbstractChromatin architecture and gene expression profile undergo tremendous reestablishment during senescence. However, the regulatory mechanism between chromatin reconstruction and gene expression in senescence remain elusive. The chromatin accessibility is an excellent perspective to reveal the latent regulatory elements. Thus, we depicted the landscapes of chromatin accessibility and gene expression during HUVECs senescence. We found that chromatin accessibilities are re-distributed during senescence. The senescence related increased accessible regions (IARs) and the decreased accessible regions (DARs) are mainly distributed in distal intergenic regions. The DARs are correlated with the function declines caused by senescence, whereas the IARs are involved in the regulation for senescence program. Moreover, the heterochromatin contributes most of IARs in senescent cells. We identified that the AP-1 transcription factors, especially ATF3 is responsible for driving chromatin accessibility reconstruction in IARs. In particular, DNA methylation is negatively correlated with chromatin accessibility during senescence. AP-1 motifs with low DNA methylation may improve their binding affinity in IARs and further opens the chromatin nearby. Our results described a dynamic landscape of chromatin accessibility whose remodeling contributes to the senescence program. And we identified a cellular senescence regulator, AP-1, which promotes senescence through organizing the accessibility profile in IARs.
Who is attracted to socially responsible organizations? Roles of job applicants' volunteer experience and motives
Authors: Choi Byoung Kwon , Moon Hyoung Koo , Joo Young Ran 
Published: August 2020

PurposeBased on the multiple domain perspective and self-identity theory, this study aims to investigate the effect of job applicants' volunteer experience on their attraction to organizations that engage in corporate social responsibility (CSR). Moreover, it examines the mediating effect of the CSR work role definition in this relationship and proposes a moderated mediation model of how the effect of volunteer experience on organizational attractiveness through the CSR work role definition differs according to other- and self-oriented motives.Design/methodology/approachHypotheses were tested with a moderated mediation model using a scenario-based questionnaire with a sample of 146 undergraduate students in South Korea.FindingsJob applicants' volunteer experience was positively related to attraction to socially responsible organizations, and the CSR work role definition mediated this relationship. The conditional indirect effect of job applicants' volunteer experience on their attraction to socially responsible organizations through the CSR work role definition was significant only for job applicants with lower other- and self-oriented motives.Practical implicationsThe study findings suggest that organizations performing CSR should examine whether job applicants have experience with volunteering activities and the motives behind their participation in such activities.Originality/valueThis study contributes to a comprehensive understanding of how job applicants are attracted to organizations that perform CSR and when such attraction is significant by considering their perception of the CSR work role definition and motives for volunteering activities.
Pivot or pirouette? Turning to emergency remote teaching in the COVID-19 pandemic
Authors: Whitakker Louise , Kleyn Nicola , Pearson Hayley 
Published: August 2020

Learning outcomes
Learning outcomes are as follows: Students will be able to demonstrate the need to understand the uncertainty faced in a crisis; demonstrate how dynamic capabilities allow an organisation to respond effectively in a time of crisis and deep uncertainty; explore how strong dynamic capabilities are required to maintain continuity of operations by enabling a shift in the current business model; and evaluate methods of mobilising resources to address needs and possible opportunities presented in a crisis.

Case overview/synopsis
Gordon Institute of Business Science (GIBS), a South African-based business school and the one of the top ranked business schools in Africa, faced a crisis in the midst of the COVID-19 pandemic. With the announcement of a national lock down, under strict conditions, and the immediate closure of the GIBS campus, the Academic Programmes had to radically shift their mode of delivery to enable students to continue with their respective programmes. When the situation was further exacerbated by the breaking of the undersea cable, the Executive Director of Academic Programmes, Professor Louise Whittaker faced the difficult decision on what to do next. The case illustrates the need for strong dynamic capabilities to foster organisational agility and to respond effectively in times of deep uncertainty or crises.

Complexity academic level
The case is positioned at a postgraduate level and would be ideal as a teaching case for business students on a Master of Business Administration programme, a specialised Master in Philosophy programme or selected executive education programmes for general managers or senior executives.

Supplementary materials
Teaching Notes are available for educators only.

Subject code
CSS: 11 Strategy.
Why people need privacy? The role of privacy fatigue in app users' intention to disclose privacy: based on personality traits
Authors: Tang Jie , Akram Umair , Shi Wenjing 
Published: August 2020

PurposeMobile Applications (App) privacy has become a prominent social problem. Compared with privacy concerns, this study examines a relatively novel concept of privacy fatigue and explores its effect on the users’ intention to disclose their personal information via mobile Apps. In addition, the personality traits are proposed as antecedents that will induce the personal perception of privacy fatigue and privacy concerns differently.Design/methodology/approachData were collected from 426 respondents. Structure equation modeling was used to test the hypotheses.FindingsThe findings describe that App users’ intention toward personal information disclosure is determined by privacy fatigue and privacy concerns, but the former has a greater impact. With minor exceptions, the two factors are also influenced by different personality traits. Specifically, neuroticism has positive effects on privacy fatigue, but agreeableness and extraversion have presented the opposite results on the two variables.Practical implicationsThis research is very scarce to examine the joint effects of privacy fatigue, privacy concerns and personality traits on App users’ disclosing intention. In doing so, these results will be of benefit to App providers and platform managers and can be the basis for a variety of follow-up studies.Originality/valueWhile previous research just focuses on privacy concerns, this study explores the critical roles of privacy fatigue and opens up a new avenue of emotion-attitude analysis that can further increase the specificity and richness of users’ privacy research. Additionally, implications for personality traits as antecedents in the impact of App users’ privacy emotions and attitudes are discussed.
Crop diversity benefits carabid and pollinator communities in landscapes with semi‐natural habitats
Authors: Aguilera Guillermo , Roslin Tomas , Miller Kirsten , Tamburini Giovanni , Birkhofer Klaus , Caballero‐Lopez Berta , Lindström Sandra Ann‐Marie , Öckinger Erik , Rundlöf Maj , Rusch Adrien , Smith Henrik G. , Bommarco Riccardo 
Published: August 2020

Abstract

In agricultural landscapes, arthropods provide essential ecosystem services such as biological pest control and pollination. Intensified crop management practices and homogenization of landscapes have led to declines among such organisms. Semi‐natural habitats, associated with high numbers of these organisms, are increasingly lost from agricultural landscapes but diversification by increasing crop diversity has been proposed as a way to reverse observed arthropod declines and thus restore ecosystem services. However, whether or not an increase in the diversity of crop types within a landscape promotes diversity and abundances of pollinating and predaceous arthropods, and how semi‐natural habitats might modify this relationship, are not well understood.

To test how crop diversity and the proportion of semi‐natural habitats within a landscape are related to the diversity and abundance of beneficial arthropod communities, we collected primary data from seven studies focusing on natural enemies (carabids and spiders) and pollinators (bees and hoverflies) from 154 crop fields in Southern Sweden between 2007 and 2017.

Crop diversity within a 1‐km radius around each field was positively related to the Shannon diversity index of carabid and pollinator communities in landscapes rich in semi‐natural habitats. Abundances were mainly affected by the proportion of semi‐natural habitats in the landscape, with decreasing carabid and increasing pollinator numbers as the proportion of this habitat type increased. Spiders showed no response to either crop diversity or the proportion of semi‐natural habitats.

Synthesis and applications. We show that the joint effort of preserving semi‐natural habitats and promoting crop diversity in agricultural landscapes is necessary to enhance communities of natural enemies and pollinators. Our results suggest that increasing the diversity of crop types can contribute to the conservation of service‐providing arthropod communities, particularly if the diversification of crops targets complex landscapes with a high proportion of semi‐natural habitats.