bluuebunny/crossref_metadata_2025_split huggingface dataset:
NK cells orchestrate splenic cDC1 migration to potentiate antiviral protective CD8+ T cell responses
Authors: Ghilas Sonia , Ambrosini Marc , Cancel Jean-Charles , Massé Marion , Lelouard Hugues , Dalod Marc , Crozat Karine 
Published: April 2020

SummaryA successful immune response relies on a tightly regulated delivery of the right signals to the right cells at the right time. Here we show that innate and innate-like lymphocytes use two mechanisms to orchestrate in time and space the functions of conventional type 1 dendritic cells (cDC1) in spleen. Early after murine cytomegalovirus infection, XCL1 production by lymphocytes with innate functions attracts red pulp cDC1 near IFN-γ-producing NK cells, generating superclusters around infected cells in the marginal zone. There, cDC1 and NK cells physically interact reinforcing their reciprocal activation. Targeted IL-12 delivery and IL-15/IL-15Rα transpresentation by cDC1 trigger NK cell activation and expansion. In return, activated NK cells deliver GM-CSF to cDC1, triggering their CCR7-dependent relocalization into the T cell zone. This NK cell-dependent licensing of cDC1 accelerates the priming of virus-specific CD8+T cells. Our findings reveal a novel mechanism through which cDC1 bridge innate and adaptive immunity.
Thiocillin and Micrococcin Exploit the Ferrioxamine Receptor ofPseudomonas aeruginosafor Uptake
Authors: Chan Derek C. K. , Burrows Lori L. 
Published: April 2020

ABSTRACTThiopeptides are a class of Gram-positive antibiotics that inhibit protein synthesis. They have been underutilized as therapeutics due to solubility issues, poor bioavailability, and lack of activity against Gram-negative pathogens. We discovered recently that a member of this family, thiostrepton, has activity againstPseudomonas aeruginosa and Acinetobacter baumanniiunder iron-limiting conditions. Thiostrepton uses pyoverdine siderophore receptors to cross the outer membrane, and combining thiostrepton with an iron chelator yielded remarkable synergy, significantly reducing the minimal inhibitory concentration. These results led to the hypothesis that other thiopeptides could also inhibit growth by using siderophore receptors to gain access to the cell. Here, we screened six thiopeptides for synergy with the iron chelator deferasirox againstP. aeruginosaand a mutant lacking the pyoverdine receptors FpvA and FpvB. Our findings suggest that thiopeptides such as thiocillin cross the outer membrane using FoxA, the ferrioxamine siderophore receptor. Other structurally related thiopeptides did not inhibit growth ofP. aeruginosa, but had greater potency against methicillin-resistantStaphylococcus aureusthan thiostrepton and related thiopeptides. These results suggest that thiopeptide structures have evolved with considerations for target affinity and entry into cells.
Cerebral cavernous malformation 1 determines YAP/TAZ signaling dependent metastatic hallmarks of prostate cancer cells
Authors: Park Sangryoung , Lee Ho-Yong , Park Hansol , Ju Young Seok , Kim Jayoung , Kim Eung-Gook , Kim Jaehong 
Published: April 2020

AbstractEnhanced Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling is correlated with the extraprostatic extension of prostate cancer. However, the mechanism by which YAP/TAZ signaling becomes hyperactive and drives prostate cancer progression is currently unclear. In this study, we demonstrated that CCM1 induces the metastasis of multiple types of prostate cancer cells by regulating YAP/TAZ signaling. Mechanistically, CCM1, a gene mutated in cerebral cavernous malformation, suppresses DDX5, which regulates the PLK1-mediated suppression of YAP/TAZ signaling, indicating that CCM1 and DDX5 are novel upstream regulators of YAP/TAZ signaling. We also revealed that higher expression of CCM1, which is uniquely found in advanced prostate cancer, is inversely correlated with metastasis-free and overall survival in patients with prostate cancer. Our findings highlight the importance of CCM1-DDX5-PLK1-YAP/TAZ signaling in the metastasis of prostate cancer cells.Statement of SignificanceOur analysis of CCM1 expression and function represents a candidate predictive biomarker for prostate cancer metastasis and provides an evidence that abnormality of CCM1 can be pathogenic in prostate cancer. Importantly, CCM1 regulation of metastasis progression appears to a common molecular event in metastatic prostate cancer cells arising in disparate genetic backgrounds.
Charge-Driven Condensation of RNA and Proteins Suggests Broad Role of Phase Separation in Cytoplasmic Environments
Authors: Dutagaci Bercem , Nawrocki Grzegorz , Goodluck Joyce , Ashkarran Ali Akbar , Hoogstraten Charles G. , Lapidus Lisa J. , Feig Michael 
Published: April 2020

ABSTRACTPhase separation processes are increasingly being recognized as important organizing mechanisms of biological macromolecules in cellular environments. Well established drivers of liquid-liquid phase separation are multi-valency and intrinsic disorder. Here, we show that globular macromolecules may condense simply based on electrostatic complementarity. More specifically, phase separation of mixtures between RNA and positively charged proteins is described from a combination of multiscale computer simulations with microscopy and spectroscopy experiments. Condensates retain liquid character and phase diagrams are mapped out as a function of molecular concentrations in experiment and as a function of molecular size and temperature via simulations. The results suggest a more general principle for phase separation that is based primarily on electrostatic complementarity without invoking polymer properties as in most previous studies. Simulation results furthermore suggest that such phase separation may occur widely in heterogenous cellular environment between nucleic acid and protein components.STATEMENT OF SIGNIFICANCELiquid-liquid phase separation has been recognized as a key mechanism for forming membrane-less organelles in cells. Commonly discussed mechanisms invoke a role of disordered peptides and specific multi-valent interactions. We report here phase separation of RNA and proteins based on a more universal principle of charge complementarity that does not require disorder or specific interactions. The findings are supported by coarse-grained simulations, theory, and experimental validation via microscopy and spectroscopy. The broad implication of this work is that condensate formation may be a universal phenomenon in biological systems.
The Viral Polymerase Complex Mediates the Interaction of vRNPs with Recycling Endosomes During SeV Assembly
Authors: Genoyer Emmanuelle , Kulej Katarzyna , Hung Chuan Tien , Thibault Patricia A. , Azarm Kristopher , Takimoto Toru , Garcia Benjamin A. , Lee Benhur , Lakdawala Seema , Weitzman Matthew D. , López Carolina B. 
Published: April 2020

ABSTRACTParamyxoviruses are negative sense single-stranded RNA viruses that comprise many important human and animal pathogens, including human parainfluenza viruses. These viruses bud from the plasma membrane of infected cells after the viral ribonucleoprotein complex (vRNP) is transported from the cytoplasm to the cell membrane via Rab11a-marked recycling endosomes. The viral proteins that are critical for mediating this important initial step in viral assembly are unknown. Here we use the model paramyxovirus, murine parainfluenza virus 1, or Sendai virus (SeV), to investigate the roles of viral proteins in Rab11a-driven virion assembly. We previously reported that infection with SeV containing high levels of copy-back defective viral genomes (DVGs) generates heterogenous populations of cells. Cells enriched in full-length virus produce viral particles containing standard or defective viral genomes, while cells enriched in DVGs do not, despite high levels of defective viral genome replication. Here we take advantage of this heterogenous cell phenotype to identify proteins that mediate interaction of vRNPs with Rab11a. We examine the role of matrix protein and nucleoprotein and determine that they are not sufficient to drive interaction of vRNPs with recycling endosomes. Using a combination of mass spectrometry and comparative protein abundance and localization in DVG- and FL-high cells, we identify viral polymerase complex components L and, specifically, its cofactor C proteins as interactors with Rab11a. We find that accumulation of these proteins within the cell is the defining feature that differentiates cells that proceed to viral egress from cells which remain in replication phases.IMPORTANCEParamyxoviruses are a family of viruses that include a number of pathogens with significant burdens on human health. Particularly, human parainfluenza viruses are an important cause of pneumonia and bronchiolitis in children for which there are no vaccines or direct acting antivirals. These cytoplasmic replicating viruses bud from the plasma membrane and coopt cellular endosomal recycling pathways to traffic viral ribonucleoprotein complexes from the cytoplasm to the membrane of infected cells. The viral proteins required for viral engagement with the recycling endosome pathway are still not known. Here we use the model paramyxovirus Sendai virus, or murine parainfluenza virus 1, to investigate the role of viral proteins in this initial step of viral assembly. We find that viral polymerase components large protein L and accessory C proteins are necessary for engagement with recycling endosomes. These findings are important in identifying viral proteins as potential targets for development of antivirals.
Spatio-temporal associations between deforestation and malaria incidence in Lao PDR
Authors: Rerolle Francois , Dantzer Emily , Lover Andrew A. , Marshall John M. , Hongvanthong Bouasy , Sturrock Hugh JW. , Bennett Adam 
Published: April 2020

AbstractAs countries in the Greater Mekong Sub-region (GMS) increasingly focus their malaria control and elimination efforts on forest-going populations, greater understanding of the relationship between deforestation and malaria incidence will be essential for programs to assess and meet their 2030 elimination goals. Leveraging village-level health facility surveillance data and forest cover data in a spatio-temporal modeling framework, we found evidence that deforestation is associated with short-term increases, but long-term decreases in confirmed malaria case incidence in Lao People’s Democratic Republic (Lao PDR). We identified strong associations with deforestation measured within 30 km of villages but not with deforestation in the near (10 km) and immediate (1 km) vicinity. Results appear driven by deforestation in densely forested areas and were more pronounced for infections with Plasmodium falciparum (P. falciparum) than for Plasmodium vivax (P. vivax). These findings highlight the influence of forest-going populations on malaria transmission in the GMS.
Hybrid software reliability model with Pareto distribution and ant colony optimization (PD–ACO)
Authors: D Sudharson , Dr Prabha 
Published: April 2020

PurposeSoftware reliability models in the past few years attracted researchers to build an accurate model in the software engineering. Testing is an important factor in the software development cycle.Design/methodology/approachAs testing improves quality and reliability of the application by identifying the bugs in it. Also, it defines the behavior and state of the product based on the defined principles and mechanisms. Conventional reliability models use statistical distributions to attain realistic features.FindingsThe ability to predict the bugs in the application during development phase itself is a proper testing practice which saves the time and increases the efficiency of the application. Efficient management and timely release of the product is based on this reliability testing and ant colony optimization (ACO)-based testing is an important optimization model which is available for testing the application.Originality/valueConventional ant colony optimization used test case generation as its common approach for testing the reliability of the application. ACO uses pheromone activity and it is related in testing of application and provides a simple positive mechanism by identifying the inactivity and precociousness.
Confirmation of a measurement model for manufacturing flexibility development practices
Authors: Mishra Ruchi 
Published: April 2020

PurposeThe study aims to conceptualize and empirically develop an instrument to measure manufacturing flexibility development practices in firms.Design/methodology/approachUsing a dataset of 315 responses, a series of procedures were used to develop, modify and refine item measures of constructs to enhance their reliability and validity. Further, following a competing model strategy, alternative models were compared to finalize the manufacturing flexibility development practices.FindingsThe study develops 36-item instrument capturing eight distinct constructs that influence manufacturing flexibility development, namely operational improvement practices, supplier integration practices, advanced manufacturing technologies, advanced human resource practices, supplier flexibility, customer integration practices, marketing and manufacturing integration practices and product-process technology integration. The derived factors exhibit an adequate level of consistency, reliability and validity.Research limitations/implicationsSince the external environment is always affected by externalities, tools and technologies used to develop flexibility may also vary over time. Therefore, the developed measurement instrument can be used over the medium term. Further, the statistical generalizability of this study cannot be drawn beyond the scope of this sample.Practical implicationsThe derived items measure and their underlying factor structure facilitates practitioners to identify areas that need attention. Practically, practitioners should strive to improve multiple factors that influence manufacturing flexibility to arrive at the full realization of flexibility.Originality/valueThis study is probably the first to develop an instrument for assessing the factors influencing the potential of manufacturing flexibility.
Leveraging service design for healthcare transformation: toward people-centered, integrated, and technology-enabled healthcare systems
Authors: Patrício Lia , Sangiorgi Daniela , Mahr Dominik , Čaić Martina , Kalantari Saleh , Sundar Sue 
Published: April 2020

PurposeThis paper explores how service design can contribute to the evolution of health service systems, moving them toward people-centered, integrated and technology-enabled care; the paper develops a research agenda to leverage service design research for healthcare transformation.Design/methodology/approachThis conceptual study starts by analyzing healthcare challenges in terms of demographic trends and economic constraints, along with the problems of lack of people-centricity, dispersion of care and slowness in incorporating emerging technologies. Then, it examines the theoretical underpinnings of service design to develop a framework for exploring how a human-centered, transformative and service systems approach can contribute to addressing healthcare challenges, with illustrative cases of service design research in healthcare being given.FindingsThe proposed framework explores how a human-centered service design approach can leverage the potential of technology and advance healthcare systems toward people-centered care; how a transformative service design approach can go beyond explanatory research of healthcare phenomena to develop innovative solutions for healthcare change and wellbeing; and how a service systems perspective can address the complexity of healthcare systems, hence moving toward integrated care.Originality/valueThis paper systematizes and develops a framework for how service design can contribute to healthcare transformation. It identifies key healthcare application areas for future service design research and pathways for advancing service design in healthcare by using new interdisciplinary bridges, methodological developments and theoretical foundations.
Parameter sensitivity analysis of stability of T-shaped rigid frame bridge by adopting swivel construction method
Authors: Wang Jiawei , sun Quansheng 
Published: April 2020

PurposeIn order not to affect the highway and railway traffic under the bridge during the construction process, bridges adopting swivel construction method are increasingly used at areas where the traffic is heavy. Previous studies are mostly conducted by assuming that the bridge is under its own stability conditions, without considering the impact of construction error, changes of external condition and wind-induced vibration on the stability of the bridge, which poses serious challenges to the bridge construction process. This paper aims to analyze the extent to which static load and fluctuating wind effect influence structural stability and to test the credibility of the structure.Design/methodology/approachA finite element calculation method is used to analyze a T-shaped rigid frame swivel bridge. A full bridge model was built, and a local model of the turntable structure established; the two are then combined means of node coupling. Subsequently, the three sensitivity indexes – deflection rate, stress change rate and the change rate of spherical hinges – are used to evaluate in what way the bridge stability is influenced under various factors.FindingsIt is found that the stability of the swivel bridge is quite sensitive to unilateral overweight, steel beam tension and wind-induced vibration effects but less sensitive to the change of bulk density. Also found is that the change of elastic modulus exerts some effects on deflection but has negligible effects on other stability indexes. Furthermore, the transverse unbalanced torque on the bridge generated by wind-induced vibration is an important factor in determining the size of the turntable, indicating that it is not just controlled by the weight of the bridge.Originality/valueAll factors affecting the stability of swivel construction are analyzed, and solutions to reduce the influence are proposed. The influence of wind-induced vibration effects on swivel construction is analyzed for the first time. It is pointed out that wind-induced vibration effects have great influence on the structure, and its influence could not be neglected.
Sharing economy: a review of the literature and a framework for future research
Authors: Wang Xuequn , Lin Xiaolin , Abdullat Amjad 
Published: April 2020

Purpose
As sharing economy has become increasingly popular, researchers from various disciplines begin to pay more attention to this important phenomenon. However, the current literature is fragmented and lacks a framework to integrate previous studies and guide future research. This study aims to systematically review the literature to better understand what one knows and what one need to know about sharing economy and provide a road map for future research in the context of sharing economy.

Design/methodology/approach
A systematic review was conducted with EBSCO and science direct database. In total, 91 studies were identified.

Findings
The review shows that previous studies focus on different stakeholders, including consumers, peer service providers, platform providers, and competitors. The authors further identify the main topics and limitations of the literature (integrated into a framework) and provide possible directions for future studies. For example, the authors find that few studies have examined individual and technical factors. The findings also show that consumers’ other activities and outcomes have received little attention. To address these limitations, future studies that examine how individual and technical characteristics influence sharing economy’s usage intention/behaviors are suggested. The authors also suggest future studies to explore other activities during the process of sharing economy services.

Research limitations/implications
The framework and directions provided can further the sharing economy research by addressing important gaps in the current literature.

Originality/value
This review identifies many opportunities for researchers to better understand the phenomenon of sharing economy.
The use of isothermal titration calorimetry to unravel chemotactic signalling mechanisms
Authors: Matilla Miguel A. , Martín‐Mora David , Krell Tino 
Published: April 2020

SummaryChemotaxis is based on the action of chemosensory pathways and is typically initiated by the recognition of chemoeffectors at chemoreceptor ligand‐binding domains (LBD). Chemosensory signalling is highly complex; aspect that is not only reflected in the intricate interaction between many signalling proteins but also in the fact that bacteria frequently possess multiple chemosensory pathways and often a large number of chemoreceptors, which are mostly of unknown function. We review here the usefulness of isothermal titration calorimetry (ITC) to study this complexity. ITC is the gold standard for studying binding processes due to its precision and sensitivity, as well as its capability to determine simultaneously the association equilibrium constant, enthalpy change and stoichiometry of binding. There is now evidence that members of all major LBD families can be produced as individual recombinant proteins that maintain their ligand‐binding properties. High‐throughput screening of these proteins using thermal shift assays offer interesting initial information on chemoreceptor ligands, providing the basis for microcalorimetric analyses and microbiological experimentation. ITC has permitted the identification and characterization of many chemoreceptors with novel specificities. This ITC‐based approach can also be used to identify signal molecules that stimulate members of other families of sensor proteins.
The Effect of Investment, LFA and Agri‐environmental Subsidies on the Components of Total Factor Productivity: The Case of Slovenian Farms
Authors: Baráth Lajos , Fertő Imre , Bojnec Štefan 
Published: April 2020

AbstractThe effect of subsidies on the performance of farms has received a great deal of attention in the literature, although results are inconclusive. Furthermore, much of the related literature examines the effect of subsidies only on technical efficiency (TE). We examine the effect of different types of subsidies on the different components of total factor productivity (TFP) in Slovenian agriculture over the period 2006–2013. We first estimate a Random Parameter Stochastic production frontier model. Then, based on the estimates of this model, we calculate and decompose the TFP index into TE, scale efficiency and technological change. Third, we apply combined difference‐in‐difference and a matching estimator to examine the effect of investment, less favoured area (LFA) and agri‐environmental (AE) subsidies on the different components of TFP. In our case, these subsidies are found to have no significant effect on either TFP or on its components.