bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recovirus NS1-2 has viroporin activity that induces aberrant cellular calcium signaling to facilitate virus replication
Authors: Strtak Alicia C. , Perry Jacob L. , Sharp Mark N. , Chang-Graham Alexandra L. , Farkas Tibor , Hyser Joseph M. 
Published: July 2019

AbstractEnteric viruses in theCaliciviridaefamily cause acute gastroenteritis in humans and animals, but the cellular processes needed for virus replication and disease remain unknown. A common strategy among enteric viruses, including rotaviruses and enteroviruses, is to encode a viral ion channel (i.e., viroporin) that is targeted to the endoplasmic reticulum (ER) and disrupts host calcium (Ca2+) homeostasis. Previous reports have demonstrated genetic and functional similarities between the nonstructural proteins of caliciviruses and enteroviruses, including the calicivirus NS1-2 protein and the 2B viroporin of enteroviruses. However, it is unknown whether caliciviruses alter Ca2+homeostasis for virus replication or whether the NS1-2 protein has viroporin activity like its enterovirus counterpart. To address these questions, we used Tulane virus (TV), a rhesus enteric calicivirus, to examine Ca2+signaling during infection and determine whether NS1-2 has viroporin activity that disrupts Ca2+homeostasis. We found that TV disrupts increases Ca2+signaling during infection and increased cytoplasmic Ca2+levels is important for efficient replication. Further, TV NS1-2 localizes to the endoplasmic reticulum (ER), the predominant intracellular Ca2+store and the NS2 region has characteristics of a viroporin domain (VPD). NS1-2 had viroporin activity in a classic bacterial functional assay and caused aberrant Ca2+signaling when expressed in mammalian cells, but truncation of the VPD abrogated these functions. Together, our data provide new mechanistic insights into the function of the NS2 region of NS1-2 and show that like many other enteric viruses, enteric caliciviruses also exploit host Ca2+signaling to facilitate their replication.ImportanceTulane virus is one of many enteric caliciviruses that cause acute gastroenteritis and diarrheal disease. Globally, enteric caliciviruses affect both humans and animals and result in >65 billion dollars per year in treatment and healthcare-associated costs, thus imposing an enormous economic burden. Recent progress has resulted in several cultivation systems (B cell, enteroid and zebrafish larvae) to study human noroviruses, but mechanistic insights into the viral factors and host pathways important for enteric calicivirus replication and infection are largely still lacking. Here we used Tulane virus, a calicivirus that is biologically similar to human noroviruses and can be cultivated in conventional cell culture, to identify and functionally validate NS1-2 as an enteric calicivirus viroporin. Viroporin-mediated calcium signaling may be a broadly utilized pathway for enteric virus replication, and its existence within caliciviruses provides a novel approach to developing antivirals and comprehensive therapeutics for enteric calicivirus diarrheal disease outbreaks.
Single-cell transcriptome profiling reveals dermal and epithelium cell fate decisions during embryonic hair follicle development
Authors: Ge Wei , Tan Shao-Jing , Wang Shan-He , Li Lan , Sun Xiao-Feng , Shen Wei , Wang Xin 
Published: July 2019

AbstractCharacterization of the morphological structure during hair follicle development has been well documented, while the current understanding of the molecular mechanisms involved in follicle development remain limited. Here, using unbiased single-cell RNA sequencing, we analyzed 15,086 single cell transcriptome profiles from E13.5 and E16.5 fetal mice, and newborn mouse (postnatal day 0, P0) dorsal skin cells. Based on t-distributed Stochastic Neighbor Embedding (tSNE) clustering, we identified 14 cell clusters from skin cells and delineated their cell identity gene expression profiles. Pseudotime ordering analysis successfully constructed epithelium/dermal cell lineage differentiation trajectory and revealed sequential activation of key regulons involved during cell fate decisions. Along with this, intercellular communication between different cell populations were inferred based on a priori knowledge of ligand-receptor pairs. Together, our findings here provide a molecular landscape during hair follicle epithelium/dermal cell lineage fate decisions, and more importantly, recapitulate sequential activation of core regulatory transcriptional factors for different cell populations during hair follicle morphogenesis.
Cell-to-cell diversification in ERBB-RAS-MAPK signal transduction that produces cell-type specific growth factor responses
Authors: Miyagi Hiraku , Hiroshima Michio , Sako Yasushi 
Published: July 2019

AbstractGrowth factors regulate cell fates, including their proliferation, differentiation, survival, and death, according to the cell type. Even when the response to a specific growth factor is deterministic for collective cell behavior, significant levels of fluctuation are often observed between single cells. Statistical analyses of single-cell responses provide insights into the mechanism of cell fate decisions but very little is known about the distributions of the internal states of cells responding to growth factors. Using multi-color immunofluorescent staining, we have here detected the phosphorylation of seven elements in the early response of the ERBB–RAS–MAPK system to two growth factors. Among these seven elements, five were analyzed simultaneously in distinct combinations in the same single cells. Although principle component analysis suggested cell-type and input specific phosphorylation patterns, cell-to-cell fluctuation was large. Mutual information analysis suggested that cells use multitrack (bush-like) signal transduction pathways under conditions in which clear cell fate changes have been reported. The clustering of single-cell response patterns indicated that the fate change in a cell population correlates with the large entropy of the response, suggesting a bet-hedging strategy is used in decision making. A comparison of true and randomized datasets further indicated that this large variation is not produced by simple reaction noise, but is defined by the properties of the signal-processing network.Author SummaryHow extracellular signals, such as growth factors (GFs), induce fate changes in biological cells is still not fully understood. Some GFs induce cell proliferation and others induce differentiation by stimulating a common reaction network. Although the response to each GF is reproducible for a cell population, not all single cells respond similarly. The question that arises is whether a certain GF conducts all the responding cells in the same direction during a fate change, or if it initially stimulates a variety of behaviors among single cells, from which the cells that move in the appropriate direction are later selected. Our current statistical analysis of single-cell responses suggests that the latter process, which is called a bet-hedging mechanism is plausible. The complex pathways of signal transmission seem to be responsible for this bet-hedging.
Single-Cell RNA-Seq Reveals Novel Mitochondria-related Musculoskeletal Cell Populations during Adult Axolotl Limb Regeneration Process
Authors: Qin Tian , Fan Chun-mei , Wang Ting-zhang , Yang Long , Shen Wei-liang , Sun Heng , Lin Jun-xin , Cucchiarini Magali , Clement Nicholas D. , Mason Christopher E. , Bunpetch Varitsara , Nakamura Norimasa , Bhonde Rameah , Clement Nicholas D. , Yin Zi , Chen Xiao 
Published: July 2019

ABSTRACTWhile the capacity to regenerate tissues or limbs is limited in mammals including humans, unlike us, axolotls are able to regrow entire limbs and major organs. The wound blastema have been extensively studied in limb regeneration. However, due to the inadequate characterization and coordination of cell subpopulations involved in the regeneration process, it hinders the discovery of the key clue for human limb regeneration. In this study, we applied unbiased large-scale single-cell RNA sequencing to classify cells throughout the adult axolotl limb regeneration process. We computationally identified 7 clusters in regenerating limbs, including the novel regeneration-specific mitochondria-related cluster supporting regeneration through energy providing and the COL2+ cluster contributing to regeneration through cell-cell interactions signals. We also discovered the dedifferentiation and re-differentiation of the COL1+/COL2+ cellular subpopulation and uncovered a COL2-mitochondria sub-cluster supporting the musculoskeletal system regeneration. On the basis of these findings, we reconstructed the dynamic single-cell transcriptome atlas of adult axolotl limb regenerative process, and identified the novel regenerative mitochondria-related musculoskeletal populations, which yielded deeper insights into the crucial interactions between cell clusters within the regenerative microenvironment.
Environmental innovation practices and operational performance
Authors: Gomez-Conde Jacobo , Lunkes Rogerio Joao , Rosa Fabricia Silva 
Published: July 2019

PurposeThe purpose of this paper is to analyze the effect of management accounting and control systems (MACS) on environmental innovation practices and operational performance. Specifically, this study relies on Simons’ levers of control (LOC) framework to investigate how managers implement environmental innovation practices. This paper hypothesizes that a forward-looking use of MACS (i.e. interactive use) triggers the implementation of environmental innovation practices, resulting in higher operational performance. Furthermore, the authors argue that the monitoring role of MACS (i.e. diagnostic use) combined with environmental training improves the effect of environmental innovation practices on operational performance.Design/methodology/approachHypotheses are examined through a questionnaire survey. The analyses are based on responses in an empirical study from 89 Brazilian hotels.FindingsEmpirical findings from a hierarchical moderated regression analysis support the hypothesized links.Originality/valueThis study contributes to the environmental management and management control literature by providing novel evidence on the roles MACS play in the field of sustainable development. Based on the LOC framework, the authors shed light on the understanding of how managers introduce and monitor environmental innovation practices, as well as also outlining the key effects of environmental training in enabling the novel abilities of managers and employees to better understand environmental data and identify novel potential environmentally friendly solutions in the case of deviations. This paper also adds to Wijethilakeet al.(2017), providing new empirical evidence on how firms design, implement and use MACS that capture institutional pressures for sustainability from multiple stakeholders.
“Opt-out” or pushed out?
Authors: Lim Wee Ling , Mohd Rasdi Roziah 
Published: July 2019

Purpose
The purpose of this study is to explore the challenges faced by married women professionals in the private sector and the factors affecting their decisions in leaving the workforce.

Design/methodology/approach
A qualitative approach was used in this study. Data were obtained using a purposive sampling method in selecting ten married women professionals based on the inclusion criteria for this study. Semi-structured interviews were conducted and the whole interview sessions were audio recorded. Thematic analysis using the constant comparative method was used in interpreting the data.

Findings
The findings of this study revealed that majority of the married women professionals leaving workforce are affected by “pushed out” factors such as workplace inflexibility, long working hours, high volume of work than “opt-out” factors, which focus on the biological and psychological “pulls” that lure women back into their traditional roles of motherhood. Most of the married women professionals interviewed had no intention to return to the workforce and had lost confidence to join back the workforce.

Research limitations/implications
This study involved married women professionals in the private sector only. As a qualitative study, it limits to voice and views of these particular subjects only and could not be generalised to other group of women.

Practical implications
The findings from this study shall enlighten all parties involved such as women professionals, HR managers and private sector organisations in strategies and plan of action towards minimising the talent drain of women professionals.

Originality/value
This paper offers new insight into debating the opt-out or pushed out factors influencing married women professionals’ decisions in leaving the workforce. It provides voice and views of women professionals who faced a predicament in making a decision about their career development.
Identifying and describing constituents of innovation ecosystems
Authors: Yaghmaie Pegah , Vanhaverbeke Wim 
Published: July 2019

PurposeInnovation ecosystems have not been defined univocally. The authors compare the different approaches to innovation ecosystems in the literature, the link with open innovation, the value creating and value capturing processes in innovation ecosystems, and the need to orchestrate them properly. In this way, the purpose of this paper is to provide a highly needed, concise overview of the state of the art in innovation ecosystem thinking.Design/methodology/approachA systematic screening of the literature searching for publications focusing on innovation ecosystems is carried out in the paper. The authors found 30 publications and compared the different approaches to innovation ecosystems: the authors classify them according to industries, the level of analysis, their central focus on innovation ecosystems, whether frameworks are developed in the publications, the main actors, focus on SMEs or large companies, the success of innovation ecosystems and the role of the orchestrator.FindingsThe authors found different approaches to innovation ecosystems in the literature. Some papers look at the link with open innovation, and others at the value creating and value capturing processes in innovation ecosystems, the role of orchestrators, etc. The authors also provide an overview about the industries, the level of analysis, the central focus of the research, the main actors in the networks and the success factors. The authors observe that most publications have been written in Europe and apply to European ecosystems. The approach in Europe is, to some extent, also different from the main focus of leading American scholars.Research limitations/implicationsThe authors compare different approaches to innovation ecosystems. This provides a highly needed understanding of the state of the art in innovation ecosystem thinking. There are some limitations as well: the paper only does a literature review, and the authors are not developing a new framework to study innovation ecosystems.Practical implicationsThe literature overview is not primarily focused on practitioners, but the tables in the paper provide a quick overview of good management practices for setting up and managing innovation ecosystems.Social implicationsInnovations ecosystems are, in some cases, established to solve major societal problems such as changes in healthcare, energy systems, etc. Therefore, they require the interaction between different types of partners including universities, research institutes and governmental agencies. Studying innovation ecosystems is crucial to facilitate social or societal changes.Originality/valueThe paper presents a highly needed overview of the literature about innovation ecosystems and a concise examination of the different aspects that are studied so far.
Entrepreneurship and the cities in a knowledge-based perspective: evidences from EU
Authors: Penco Lara , Ivaldi Enrico , Bruzzi Carolina , Musso Enrico 
Published: July 2019

Purpose
The purpose of this paper is to answer the following research questions: Is the knowledge of a city environment a stimulus for entrepreneurship? Which knowledge profiles of cities are more propulsive in order to stimulate entrepreneurship?

Design/methodology/approach
In order to answer the aforementioned research questions, two multidimensional indexes have been created: Knowledge-Based City Developing Entrepreneurship and Entrepreneurship (ENT). The sample includes all capital cities in the EU28. The presence of cities from EU28 countries is important to foster the entrepreneurial attitude in each European Country. The authors have also included 32 non-capital cities in the EU that are important hubs, contributing to a sample formed of 60 cities.

Findings
The empirical results show that the social and cultural environment may significantly improve the entrepreneurship in EU cities, more than others factors that are usually connected to economic development.

Originality/value
The work tries to contribute to the debate on urban economic development and entrepreneurship, providing implication for academics and urban policy makers.
A multiscale method for producing homogenized drag laws of a permeable medium by conflating experimental data with Lattice-Boltzmann simulations
Authors: Clausse Alejandro , Silin Nicolás , Boroni Gustavo 
Published: July 2019

Purpose
The purpose of this paper is to obtain a permeability law of a gas flow through a permeable medium using particle image velocimetry experimental data as primal information, which is conflated with numerical calculations by means of a multi-scale method.

Design/methodology/approach
The D2Q9 single-relaxation-time Lattice Boltzmann model (LBM) implemented in GPU is used for the numerical calculations. In a first homogenized micro-scale, the drag forces are emulated by means of an effective Darcy law acting only in the close neighborhood of the solid structures. A second mesoscopic level of homogenization makes use of the effective drag forces resulting from the first-scale model.

Findings
The procedure is applied to an experiment consisting of a regular array of wires. For the first level of homogenization, an effective drag law of the individual elemental obstacles is produced by conflating particle image velocimetry measurements of the flow field around the wires and numerical calculations performed with a GPU implementation of the LBM. In the second homogenization, a Darcy–Forchheimer correlation is produced, which is used in a final homogenized LBM model.

Research limitations/implications
The numerical simulations at the first level of homogenization require a substantial amount of calculations, which in the present case were performed by means of the computational power of a GPU.

Originality/value
The homogenization procedure can be extended to other permeable structures. The micro-scale-level model retrieves the fluid-structure forces between the flow and the obstacles, which are difficult to obtain experimentally either from direct measurement or by indirect assessment from velocity measurements.
Numerical simulation of time-fractional partial differential equations arising in fluid flows via reproducing Kernel method
Authors: Abu Arqub Omar 
Published: July 2019

Purpose
The subject of the fractional calculus theory has gained considerable popularity and importance due to their attractive applications in widespread fields of physics and engineering. The purpose of this paper is to present results on the numerical simulation for time-fractional partial differential equations arising in transonic multiphase flows, which are described by the Tricomi and the Keldysh equations of Robin functions types.

Design/methodology/approach
Those resulting mathematical models are solved by using the reproducing kernel method, which provide appropriate solutions in term of infinite series formula. Convergence analysis, error estimations and error bounds under some hypotheses, which provide the theoretical basis of the proposed method are also discussed.

Findings
The dynamical properties of these numerical solutions are discussed and the profiles of several representative numerical solutions are illustrated. Finally, the prospects of the gained results and the method are discussed through academic validations.

Originality/value
In this paper and for the first time: the authors presented results on the numerical simulation for classes of time-fractional PDEs such as those found in the transonic multiphase flows. The authors applied the reproducing kernel method systematically for the numerical solutions of time-fractional Tricomi and Keldysh equations subject to Robin functions types.
Quality of maternal and child health: fresh evidence from India
Authors: Kumar Naresh , Rani Ritu 
Published: July 2019

Purpose
The purpose of this paper is to examine the regional variations in maternal and child health all over India. The Maternal and Child Health Index (MCHI) is constructed to find the extent of variations in maternal and child health status for the States and Union Territories (UTs) of India.

Design/methodology/approach
The Wroclow taxonomic technique was used to construct the MCHI for the States and UTs of India. In all, 29 variables were selected for the construction of MCHI. All the variables were taken from National Family Health Survey-4 (NFHS, 2017) of India.

Findings
The findings suggest that there are wide variations in MCHI all over India. In India, Kerala topped in terms of MCHI followed by Jammu & Kashmir. Nagaland is on the bottom of the list followed by Bihar and Uttar Pradesh. High values of MCHI (> 0.4) are posing a serious concern for all States/UTs in India.

Social implications
The existence of inequality in MCHI for India is truly posing a serious inquiry regarding the healthcare system in India. The outcome of the study demands that time has come to adopt a human rights approach to the right to health in India. The findings of the study could be used by the health policy makers in India.

Originality/value
This study shows the existence of wide variations in the quality of maternal and child health all over India. The quantification of the quality of maternal and child health is needed to improve the health of the population in India. Little research has been done on the issue of quality of maternal and child health in India. This study is an important contribution to the current knowledge of quality of maternal and child health in India.