bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spike Protein of SARS-CoV-2 Activates Macrophages and Contributes to Induction of Acute Lung Inflammations in Mice
Authors: Cao Xiaoling , Tian Yan , Nguyen Vi , Zhang Yuping , Gao Chao , Yin Rong , Carver Wayne , Fan Daping , Albrecht Helmut , Cui Taixing , Tan Wenbin 
Published: December 2020

AbstractBackgroundCoronavirus disease 2019 (COVID-19) patients exhibit multiple organ malfunctions with a primary manifestation of acute and diffuse lung injuries. The Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to mediate viral entry into host cells; however, whether it can be cellularly pathogenic and contribute to pulmonary hyper-inflammations in COVID-19 is not well known.Methods and FindingsIn this study, we developed a Spike protein-pseudotyped (Spp) lentivirus with the proper tropism of SARS-CoV-2 Spike protein on the surface and tracked down the fate of Spp in wild type C57BL/6J mice receiving intravenous injection of the virus. A lentivirus with vesicular stomatitis virus glycoprotein (VSV-G) was used as the control. Two hours post-infection (hpi), Spp showed more than 27-75 times more viral burden in the lungs than other organs; it also exhibited about 3-5 times more viral burden than VSV-G lentivirus in the lungs, liver, kidney and spleen. Acute pneumonia was evident in animals 24 hpi. Spp lentivirus was mainly found in LDLR+macrophages and pneumocytes in the lungs, but not in MARC1+macrophages. IL6, IL10, CD80 and PPAR-γ were quickly upregulated in response to infection of Spp lentivirus in the lungsin vivoas well as in macrophage-like RAW264.7 cellsin vitro. We further confirmed that forced expression of the Spike protein in RAW264.7 cells could significantly increase the mRNA levels of the same panel of inflammatory factors.ConclusionsOur results demonstrate that the Spike protein of SARS-CoV-2 alone can induce cellular pathology, e.g. activating macrophages and contributing to induction of acute inflammatory responses.
Inhibiting cough by silencing large pore-expressing airway sensory neurons with a charged sodium channel blocker
Authors: Tochitsky Ivan , Jo Sooyeon , Andrews Nick , Kotoda Masakazu , Doyle Benjamin , Shim Jaehoon , Talbot Sebastien , Roberson David , Lee Jinbo , Haste Louise , Jordan Stephen M. , Levy Bruce D. , Bean Bruce P. , Woolf Clifford J. 
Published: December 2020

AbstractAlthough multiple diseases of the respiratory system cause cough, there are few effective treatments for this common condition. We previously developed a strategy to treat pain and itch via the long-lasting inhibition of nociceptor sensory neurons with QX-314, a cationic sodium channel blocker that selectively enters only into activated nociceptors by permeating through the endogenous TRPV1 and TRPA1 large pore ion channels they express. In this study we design and characterize BW-031, a novel cationic compound with ∼6-fold greater potency than QX-314 for inhibiting sodium channels when introduced inside cells and with minimal extracellular activity. We show that inhalation of aerosolized BW-031 effectively inhibits citric acid-induced cough in an allergic inflammation guinea pig cough model. These data support the use of charged sodium channel blockers for the selective inhibition of airway sensory neurons with activated large pore channels as a novel targeted therapy for treating cough.
L-DOPA modulates activity in the vmPFC, Nucleus Accumbens and VTA during threat extinction learning in humans
Authors: Esser Roland , Korn Christoph W. , Ganzer Florian , Haaker Jan 
Published: December 2020

AbstractLearning to be safe is central for adaptive behaviour when threats are no longer present. Detecting the absence of an expected threat is key for threat extinction learning and an essential process for the behavioural treatment of anxiety related disorders. One possible mechanism underlying extinction learning is a dopaminergic mismatch signal that encodes the absence of an expected threat. Here we show that such a dopamine-related pathway underlies extinction learning in humans. Dopaminergic enhancement via administration of L-DOPA (vs. Placebo) was associated with reduced retention of differential psychophysiological threat responses at later test, which was mediated by activity in the ventromedial prefrontal cortex that was specific to extinction learning. L-DOPA administration enhanced signals at the time-point of an expected, but omitted threat in extinction learning within the nucleus accumbens, which were functionally coupled with the ventral tegmental area and the amygdala. Computational modelling of threat expectancies further revealed prediction error encoding in nucleus accumbens that was reduced when L-DOPA was administered. Our results thereby provide evidence that extinction learning is influenced by L-DOPA and provide a mechanistic perspective to augment extinction learning by dopaminergic enhancement in humans.Summary COI statementNo conflict of interest for any of the authors. The funder had no role in the design of the study, the collection and analysis of data, or the preparation of the manuscript.
Selective increase of functional network connectivity in Arc-positive neuronal engrams after long-term potentiation
Authors: Jiang Yuheng , VanDongen Antonius M.J. 
Published: December 2020

ABSTRACTNew tools in optogenetics and molecular biology have culminated in recent studies which mark immediate-early gene (IEG)-expressing neurons as memory traces or engrams. Although the activity-dependent expression of IEGs has been successfully utilised to label memory traces, their roles in engram specification is incompletely understood. Outstanding questions remain as to whether expression of IEGs can interplay with network properties such as functional connectivity and also if neurons expressing different IEGs are functionally distinct. We investigated the expression of Arc and c-Fos, two commonly utilised IEGs in memory engram specification, in cultured hippocampal neurons. After pharmacological induction of long-term potentiation (LTP) in the network, we noted an emergent network property of refinement in functional connectivity between neurons, characterized by a global down-regulation of network connectivity, together with strengthening of specific connections. Subsequently, we show that Arc expression correlates with the effects of network refinement, with Arc-positive neurons being selectively strengthened. Arc positive neurons were also found to be located in closer physical proximity to each other in the network. While the expression pattern of IEGs c-Fos and Arc strongly overlaps, Arc was more selectively expressed than c-Fos. These IEGs also act together in coding information about connection strength pruning. These results demonstrate important links between IEG expression and network connectivity, which serve to bridge the gap between cellular correlates and network effects in learning and memory.
Trafficking regulator of GLUT4-1 (TRARG1) is a GSK3 substrate
Authors: Duan Xiaowen , Norris Dougall M. , Humphrey Sean J. , Yang Pengyi , Cooke Kristen C. , Bultitude Will P. , Parker Benjamin L. , Conway Olivia J. , Burchfield James G. , Krycer James R. , Brodsky Frances M. , James David E. , Fazakerley Daniel J. 
Published: December 2020

AbstractTrafficking regulator of GLUT4-1, TRARG1, positively regulates insulin-stimulated GLUT4 trafficking and insulin sensitivity. However, the mechanism(s) by which this occurs remain(s) unclear. Using biochemical and mass spectrometry analyses we found that TRARG1 is dephosphorylated in response to insulin in a PI3K/Akt-dependent manner and is a novel substrate for GSK3. Priming phosphorylation of murine TRARG1 at serine 84 allows for GSK3-directed phosphorylation at serines 72, 76 and 80. A similar pattern of phosphorylation was observed in human TRARG1, suggesting that our findings are translatable to human TRARG1. Pharmacological inhibition of GSK3 increased cell surface GLUT4 in cells stimulated with a submaximal insulin dose, and this was impaired followingTrarg1knockdown, suggesting that TRARG1 acts as a GSK3-mediated regulator in GLUT4 trafficking. These data place TRARG1 within the insulin signaling network and provide insights into how GSK3 regulates GLUT4 trafficking in adipocytes.
Repression of MUC1 promotes expansion and suppressive function of myeloid-derived suppressor cells in pancreatic ductal adenocarcinoma and breast cancer murine models
Authors: Mahnaz S. , Roy L. Das , Bose M. , De C. , Nath S. , Mukherjee P. 
Published: December 2020

ABSTRACTMyeloid-derived suppressor cells (MDSCs) are immature myeloid cells that are responsible for immunosuppression in tumor microenvironment. Here we report the impact of mucin 1 (MUC1), a transmembrane glycoprotein, on proliferation and functional activity of MDSCs. To determine the role of MUC1 in MDSC phenotype, we analyzed MDSCs derived from wild type (WT) and MUC1-knockout (MUC1KO) mice bearing pancreatic ductal adenocarcinoma KCKO and breast cancer C57MG xenografts. We observed enhanced tumor growth in MUC1KO mice compared to WT mice in both pancreatic KCKO and breast C57MG cancer models due to increased MDSC population and enrichment of Tregs in tumor microenvironment. Our current study shows that knockdown of MUC1 in MDSCs promotes proliferation and immature suppressive phenotype indicated by increased level of iNOS, ARG1 activity and TGF-β secretion under cancer conditions. Increased activity of MDSCs leads to repression of IL-2 and IFN-ɣ production by T-cells. We were able to find that MDSCs from MUC1KO mice have higher levels of c-Myc and activated pSTAT3 as compared to MUC1 WT mice, that are signaling pathways leading to increased survival, proliferation and prevention of maturation. In summary, MUC1 regulates signaling pathways that maintain immunosuppressive properties of MDSCs. Thus, immunotherapy must target only tumor associated MUC1 on epithelial cells and not MUC1 on hematopoietic cells to avoid expansion and suppressive functions of MDSC.
Mouse embryonic stem cells switch migratory behaviour during early differentiation
Authors: Aspalter Irene M. , Pönisch Wolfram , Chalut Kevin J. , Paluch Ewa K. 
Published: December 2020

AbstractDevelopment relies on a series of precisely orchestrated cell fate changes. While studies of fate transitions often focus on changes in gene regulatory networks, most transitions are also associated with changes in cell shape and cell behaviour. Here, we investigate changes in migratory behaviour in mouse embryonic stem (ES) cells during their first developmental fate transition, exit from ES cell state. We show that naïve pluripotent ES cells cannot efficiently migrate on 2-dimensional substrates but are able to migrate in an amoeboid fashion when placed in confinement. Exit from ES cell state, typically characterised by enhanced cell spreading, is associated with decreased migration in confinement and acquisition of mesenchymal-like migration on 2D substrates. Interestingly, confined, amoeboid-like migration of ES cells strongly depends on Myosin IIA, but not Myosin IIB. In contrast mesenchymal-like migration of cells exiting the ES cell state does not depend on Myosin motor activity but relies on the activity of the Arp2/3 complex. Together, our data suggest that during early differentiation, cells undergo a switch in the regulation of the actin cytoskeleton, leading to a transition from amoeboid-to mesenchymal-like migration.Summary statementNaïve mouse embryonic stem cells display amoeboid-like migration in confinement, but switch to mesenchymal-like migration as they exit the ES cell state.
Comparative neurotranscriptomics reveal widespread species differences associated with bonding
Authors: Tripp Joel A , Berrio Alejandro , McGraw Lisa A , Matz Mikhail , Davis Jamie K , Inoue Kiyoshi , Thomas James W , Young Larry J , Phelps Steven M 
Published: December 2020

AbstractBackgroundPair bonding with a reproductive partner is rare among mammals but is an important feature of human social behavior. Decades of research on monogamous prairie voles (Microtus ochrogaster), along with comparative studies using the related non-bonding meadow vole (M. pennsylvanicus), have revealed many of the neural and molecular mechanisms necessary for pair-bond formation in that species. However, these studies have largely focused on just a few neuromodulatory systems. To test the hypothesis that neural gene expression differences underlie differential capacities to bond, we performed RNA-sequencing on tissue from three brain regions important for bonding and other social behaviors across bond-forming prairie voles and non-bonding meadow voles. We examined gene expression in the amygdala, hypothalamus, and combined ventral pallidum/nucleus accumbens in virgins and at three time points after mating to understand species differences in gene expression at baseline, in response to mating, and during bond formation.ResultsWe first identified species and brain region as the factors most strongly associated with gene expression in our samples. Next, we found gene categories related to cell structure, translation and metabolism that differed in expression across species in virgins, as well as categories associated with cell structure, synaptic and neuroendocrine signaling, and transcription and translation that varied among the focal regions in our study. Additionally, we identified genes that were differentially expressed across species after mating in each of our regions of interest. These include genes involved in regulating transcription, neuron structure, and synaptic plasticity. Finally, we identified modules of co-regulated genes that were strongly correlated with brain region in both species, and modules that were correlated with post-mating time points in prairie voles but not meadow voles.ConclusionsThese results reinforce the importance of pre-mating differences that confer the ability to form pair bonds in prairie voles but not promiscuous species such as meadow voles. Gene ontology analysis supports the hypothesis that pair-bond formation involves transcriptional regulation, and changes in neuronal structure. Together, our results expand knowledge of the genes involved in the pair bonding process and open new avenues of research in the molecular mechanisms of bond formation.
Impact of real mirror profiles inside a split-and-delay unit on the spatial intensity profile in pump/probe experiments at the European XFEL
Authors: Kärcher V. , Roling S. , Samoylova L. , Buzmakov A. , Zastrau U. , Appel K. , Yurkov M. , Schneidmiller E. , Siewert F. , Zacharias H. 
Published: December 2020

For the High-Energy-Density (HED) beamline at the SASE2 undulator of the European XFEL, a hard X-ray split-and-delay unit (SDU) has been built enabling time-resolved pump/probe experiments with photon energies between 5 keV and 24 keV. The optical layout of the SDU is based on geometrical wavefront splitting and multilayer Bragg mirrors. Maximum delays between Δτ = ±1 ps at 24 keV and Δτ = ±23 ps at 5 keV will be possible. Time-dependent wavefront propagation simulations were performed by means of the Synchrotron Radiation Workshop (SRW) software in order to investigate the impact of the optical layout, including diffraction on the beam splitter and recombiner edges and the three-dimensional topography of all eight mirrors, on the spatio-temporal properties of the XFEL pulses. The radiation is generated from noise by the code FAST which simulates the self-amplified spontaneous emission (SASE) process. A fast Fourier transformation evaluation of the disturbed interference pattern yields for ideal mirror surfaces a coherence time of τc = 0.23 fs and deduces one of τc = 0.21 fs for the real mirrors, thus with an error of Δτ = 0.02 fs which is smaller than the deviation resulting from shot-to-shot fluctuations of SASE2 pulses. The wavefronts are focused by means of compound refractive lenses in order to achieve fluences of a few hundred mJ mm−2 within a spot width of 20 µm (FWHM) diameter. Coherence effects and optics imperfections increase the peak intensity between 200 and 400% for pulse delays within the coherence time. Additionally, the influence of two off-set mirrors in the HED beamline are discussed. Further, we show the fluence distribution for Δz = ±3 mm around the focal spot along the optical axis. The simulations show that the topographies of the mirrors of the SDU are good enough to support X-ray pump/X-ray probe experiments.
Tax avoidance and firm risk in China: a pitch
Authors: Cao Yuqiang , Feng Zhuoan , Lu Meiting , Shan Yaowen 
Published: December 2020

Purpose
This paper aims to provide a critical discussion of the application of the research pitching template developed by Professor Robert Faff to a research topic of tax avoidance and firm risk. This letter provides a brief commentary on using the pitching template and discusses personal reflections on the pitching process.

Design/methodology/approach
This pitching research letter applies Faff’s pitching template and provides a critical commentary of the pitching process.

Findings
The team found that Faff’s pitching template is a valuable tool for conceiving research ideas. It helped the authors to identify, develop and articulate key aspects of the project. Further, they believe that completing the template was a beneficial and rewarding exercise, especially for early-career researchers.

Originality/value
This pitching research letter is tied to the team’s research idea that was pitched at the 2020 AFAANZ “Shark Tank” event. It provides original commentary on the use of Faff’s pitching template. It is not meant to retrofit published papers.
Adopting management control systems through CSR strategic integration and investigating its impact on company performance: evidence from Indonesia
Authors: Rinawiyanti Esti Dwi , Huang Xueli , As-Saber Sharif 
Published: December 2020

Purpose
This paper aims to investigate the extent to which the management control systems (MCS) adoption in corporate social responsibility (CSR) integration into business strategy has an impact on companies’ performance.

Design/methodology/approach
Using a sample of 435 Indonesian manufacturing companies, partial least squares structural equation modelling was used to investigate the impact of CSR strategic integration on companies’ performance based on the contingency and stakeholder theories.

Findings
The findings reveal CSR strategic integration has a positive and significant impact on companies’ performance, including employee, operating and financial performance and the company size can positively moderate the impact of this integration on both its operating and financial performance.

Practical implications
The findings can encourage managers to adopt MCS by undertaking CSR at the strategic level, resulting in superior performance, both socially and financially.

Social implications
Employee performance and operating performance can significantly mediate the effect of strategic integration on financial performance.

Originality/value
The paper suggests that adopting MCS through CSR strategic integration could improve company performance socially and financially. This is the very first study on this issue from an Indonesian perspective.
Effect of core and peripheral product line extensions on overall product line revenue
Authors: Cho Jihoon , Janda Swinder 
Published: December 2020

Purpose
Firms often use upward product line extensions to achieve gains in brand evaluations and in overall demand. Despite the prevalence of such extensions, previous research has provided little guidance about how upward line extensions influence overall revenue when they are launched as a core product as opposed to a peripheral product. The purpose of this study is to fill this research gap.

Design/methodology/approach
Using data from the quick service restaurant industry, this study looks at the effects of upwardly extended core and peripheral products on product line revenue. The empirical study uses a quasi-experiment to compare customer purchases across the pre- and post-launch of upward line extensions.

Findings
The results of this study reveal that launching core and peripheral products as upward line extensions can each increase total product line revenue. In addition, findings illustrate that as compared to a core launch, this total product line revenue increase is substantially higher in the case of a peripheral launch.

Research limitations/implications
First, the estimated model does not include supply availability and competition. Second, the data span only six months and this restriction prohibits us from investigating alternative sources of the causal effect. Third, the empirical setting in this study is limited to financial data in the quick service restaurant industry as a proxy of actual behavior. Finally, given that customers are not randomly assigned to treatment and control groups, the author is unable to definitively rule out the effect of unobservable attributes.

Practical implications
The findings suggest that firms should prioritize peripheral upward line extensions but use both types considering resource constraints (cost and human resources) and strategic importance to the firm.

Originality/value
This study bolsters the extant literature related to upward product line extensions by providing an empirical framework that evaluates the causal effect of upward line extension on total revenue, using field data in a real-life setting (as opposed to survey or lab experiment data) and actual firm revenue (as opposed to a perceptual outcome measure such as behavioral intentions). In addition, findings contribute to the new product development literature.
A study of millennials' preferred work-related attributes and retention
Authors: Pasko Raymond , Maellaro Rosemary , Stodnick Michael 
Published: December 2020

PurposeThe purpose of this study is to examine the differences in preferred work-related attributes across generational cohorts. Specific focus is given to investigating whether millennials have different preferences than previous generations.Design/methodology/approachThis study uses cross-sectional survey data of 300 employees of a large firm in the southwest USA. Conjoint analysis is used to collect employee responses that are then subjected to analysis of variance (ANOVA).FindingsThe results of this study demonstrate that employees from different generations have significantly different preferences on four work-related attributes: job security, potential for advancement, work/life balance and company leadership.Research limitations/implicationsThis study extends the generational cohort theory by employing psychological contract theory to discover and explain significant differences in preferences for varying work-related attributes for different generations. Like much cross-sectional research, these findings have to be validated and generalized.Practical implicationsFirms can use the results of this study to help understand how different generations value different work-related attributes, thus helping improve employee satisfaction and retention.Originality/valueThe originality of this research lies in its very unique approach, conjoint analysis, to be one of the first studies to test empirically the preferences for work-related attributes across generational cohorts. It lays the foundation for future research to expand upon while also giving practicing managers a useful tool to understand the needs of their employees.