bluuebunny/crossref_metadata_2025_split huggingface dataset:
VAMP8 contributes to TRIM6-mediated type-I interferon antiviral response during West Nile virus infection
Authors: Atkins Colm , Tol Sarah van , Bharaj Preeti , Rajsbaum Ricardo , Freiberg Alexander N. 
Published: December 2018

ABSTRACTMembers of the tripartite motif (TRIM) family of E3 ubiquitin ligases regulate immune pathways including the antiviral type I interferon (IFN-I) system. Previously, we demonstrated that TRIM6 is involved in IFN-I induction and signaling. In absence of TRIM6 function, optimal IFN-I signaling is reduced, allowing increased replication of interferon-sensitive viruses. Despite numerous mechanisms to restrict vertebrate host’s IFN-I response, West Nile Virus (WNV) replication is sensitive to pre-treatment with IFN-I. However, the regulators and products of the IFN-I pathway important in regulating WNV replications are incompletely defined. Consistent with WNV’s sensitivity to IFN-I, we found that in TRIM6 knockout (TRIM6 KO) A549 cells WNV replication is significantly increased. Additionally, induction of Ifnb mRNA was delayed and the expression of several IFN-stimulated genes (ISGs) was reduced in TRIM6 KO cells. IFNβ pre-treatment was more effective in protecting against subsequent WNV infection in wt cells, indicating that TRIM6 contributes to the establishment of an IFN-induced antiviral response against WNV. Using next generation sequencing, we identified potential factors involved in this TRIM6-mediated antiviral response. One identified gene, VAMP8, is a soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) in the vesicle-associated membrane protein subfamily. Knockdown of VAMP8 resulted in reduced STAT1 phosphorylation and impaired induction of several ISGs following WNV infection or IFNβ treatment. Therefore, VAMP8 is a novel gene involved in the regulation of IFN-I signaling, and its expression is dependent on TRIM6 function. Overall, these results indicate that TRIM6 contributes to the antiviral response against WNV by regulating the IFN-I system.IMPORTANCEWNV is a mosquito-borne flavivirus that poses threat to human health across large discontinuous areas throughout the world. Infection with WNV results in febrile illness, which can progress to severe neurological disease. Currently, there are no approved treatment options to control WNV infection. Understanding the cellular immune responses that regulate viral replication is important in diversifying the resources available to control WNV. Here we show that the elimination of TRIM6 in human cells results in an increase in WNV replication and alters the expression and function of other components of the IFN-I pathway through VAMP8. Dissecting the interactions between WNV and host defenses both informs basic molecular virology and promotes the development of host- and viral-targeted antiviral strategies.
Shallow MinION sequencing to assist de novo assembly of the Streptococcus agalactiae genome
Authors: Hernandez-Beeftink Tamara , Rodriguez-Perez Hector , Usera Ana Díaz-de , Gonzalez-Montelongo Rafaela , Lorenzo-Salazar José M. , Lorenzo-Díaz Fabián , Flores Carlos 
Published: December 2018

AbstractDespite the reduced read length, the so-called Next-Generation Sequencing (NGS) of second-generation has allowed rapid and complete genome characterization of many species. MinION (Oxford Nanopore Technologies), a portable third-generation NGS device, enables sequencing of long DNA fragments at low cost. Here we used a low-coverage MinION sequencing in combination with short-read NGS to improve genome assembly. We tested this possibility by using MinION R9.0 with Rapid 1D kit and MiSeq with >300X paired-end 300 bp reads (Illumina, Inc.) for the genome assembly of a Streptococcus agalactiae clinical isolate (2.2 Mb). With as few as 1,171 MinION reads that covered the genome at 2.4X (the longest read being 186 Kb long), the hybrid assembly combining MinION and Illumina reads increased the N50 by 4.9-fold compared to the assembly using Illumina data alone. Almost 50% of the genome was represented into a single contig (1.02 Mb). Besides, this allowed the full reconstruction of mobile elements, including a plasmid, and improved gene annotation. Taken together, our results support that shallow MinION sequencing combined with high-throughput second-generation NGS constitutes a cost-efficient strategy for the assembly of whole genomes.
Novitski’s Distal shift in Paracentric Inversion Evolution
Authors: Koury Spencer A. 
Published: December 2018

AbstractInDrosophila pseudoobscurayounger chromosomal inversions tend to be found distal to older inversions. By examining phylogenetic series of overlapping inversions for 134 gene arrangements of 13 chromosomes this pattern was extended to five additionalDrosophilaspecies. This distinct pattern arose repeatedly and independently in all six species and likely reflects an underlying principle of chromosome evolution. In this study it is illustrated how transmission of distal inversions isalwaysfavored in female meiosis when crossing over in homosequential regions of overlapping inversions generates asymmetric dyads. This cytogenetic mechanism for female meiotic drive is described in detail and advanced as an explanation for the distal shift in phylogenetic series of overlapping inversions as well as several better known patterns in the evolution of serially inverted chromosomes.
Geographic variation and bias in polygenic scores of complex diseases and traits in Finland
Authors: Kerminen Sini , Martin Alicia R. , Koskela Jukka , Ruotsalainen Sanni E. , Havulinna Aki S. , Surakka Ida , Palotie Aarno , Perola Markus , Salomaa Veikko , Daly Mark J. , Ripatti Samuli , Pirinen Matti 
Published: December 2018

AbstractPolygenic scores (PS) are becoming a useful tool to identify individuals with high genetic risk for complex diseases and several projects are currently testing their utility for translational applications. It is also tempting to use PS to assess whether genetic variation can explain a part of the geographic distribution of a phenotype. However, it is not well known how population genetic properties of the training and target samples affect the geographic distribution of PS. Here, we evaluate geographic differences, and related biases, of PS in Finland with geographically well-defined sample of 2,376 individuals from the National FINRISK study. First, we detect geographic differences in PS for coronary artery disease (CAD), rheumatoid arthritis, schizophrenia, waits-hip ratio (WHR), body-mass index (BMI) and height, but not for Crohn’s disease or ulcerative colitis. Second, we use height as a model trait to thoroughly assess the possible population genetic biases in PS and apply similar approaches to the other phenotypes. Most importantly, we detect suspiciously large accumulation of geographic differences for CAD, WHR, BMI and height, suggesting bias arising from population genetic structure rather than from a direct genotype-phenotype association. This work demonstrates how sensitive the geographic patterns of current PS are for small biases even within relatively homogenous populations and provides simple tools to identify such biases. A thorough understanding of the effects of population genetic structure on PS is essential for translational applications of PS.
The shape of density dependence and the relationship between population growth, intraspecific competition and equilibrium population density
Authors: Fronhofer Emanuel A. , Govaert Lynn , O’Connor Mary I. , Schreiber Sebastian J. , Altermatt Florian 
Published: December 2018

AbstractThe logistic growth model is one of the most frequently used formalizations of density dependence affecting population growth, persistence and evolution. Ecological and evolutionary theory and applications to understand population change over time often include this model. However, the assumptions and limitations of this popular model are often not well appreciated.Here, we briefly review past use of the logistic growth model and highlight limitations by deriving population growth models from underlying consumer-resource dynamics. We show that the logistic equation likely is not applicable to many biological systems. Rather, density-regulation functions are usually non-linear and may exhibit convex or both concave and convex curvatures depending on the biology of resources and consumers. In simple cases, the dynamics can be fully described by the continuous-time Beverton-Holt model. More complex consumer dynamics show similarities to a Maynard Smith-Slatkin model.Importantly, we show how population-level parameters, such as intrinsic rates of increase and equilibrium population densities are not independent, as often assumed. Rather, they are functions of the same underlying parameters. The commonly assumed positive relationship between equilibrium population density and competitive ability is typically invalid. As a solution, we propose simple and general relationships between intrinsic rates of increase and equilibrium population densities that capture the essence of different consumer-resource systems.Relating population level models to underlying mechanisms allows us to discuss applications to evolutionary outcomes and how these models depend on environmental conditions, like temperature via metabolic scaling. Finally, we use time-series from microbial food chains to fit population growth models and validate theoretical predictions.Our results show that density-regulation functions need to be chosen carefully as their shapes will depend on the study system’s biology. Importantly, we provide a mechanistic understanding of relationships between model parameters, which has implications for theory and for formulating biologically sound and empirically testable predictions.
Replication dynamics of individual loci in single living cells reveal variation of stochasticity
Authors: Duriez Bénédicte , Chilaka Sabarinadh , Bercher Jean-François , Hercul Eslande , Boggetto Nicole , Prioleau Marie-Noëlle 
Published: December 2018

AbstractEukaryotic genomes are replicated under the control of a highly sophisticated program during the restricted time period corresponding to S-phase. The most widely used replication timing assays, which are performed on populations of millions of cells, suggest that most of the genome is synchronously replicated on homologous chromosomes. We investigated the stochastic nature of this temporal program, by comparing the precise replication times of allelic loci within single vertebrate cells progressing through S-phase at six loci replicated from very early to very late. We show that replication timing is strictly controlled for the three loci replicated in the first half of S-phase. Out of the three loci replicated in the second part of S-phase, two present a significantly more stochastic pattern. Surprisingly, we find that the locus replicated at the very end of S-phase, presents stochasticity similar to those replicated in early S-phase. We suggest that the richness of loci in efficient origins of replication, which decreases from early-to late-replicating regions, may underlie the variation of timing control during S-phase.
Does protein A mirror image exist in solution? Outline of an experimental design aimed to detect it
Authors: Martin Osvaldo A. , Vorobjev Yury , Scheraga Harold A. , Vila Jorge A. 
Published: December 2018

ABSTRACTThere is abundant theoretical evidence indicating that a mirror image of ProteinA may occur during the protein folding process. However, as to whether such mirror image exists in solution is an unsolved issue. Here we provide outline of an experimental design aimed to detect the mirror image of Protein A in solution. The proposal is based on computational simulations indicating that the use of a mutant of protein A, namely 01 OH, could be used to detect the mirror image conformation in solution. Our results indicate that the native conformation of the protein A should have a pKa, for the 01 OH mutant, at r06.2, while the mirror image conformation should have a pKa close to ≈7.3. Naturally, if all the population is in the native state for the 01 OH mutant, the pKa should be ≈6.2, while, if all are in the mirror image state, it would be ≈7.3, and, if it is a mixture, the pKa should be larger than 6.2, presumably in proportion to the mirror population. In addition, evidence is provided indicating the tautomeric distribution of H1O must also change between the native and mirror conformations. Although this may not be completely relevant for the purpose of determining whether the protein A mirror image exists in solution, it could provide valuable information to validate the pKa findings. We hope this proposal will foster experimental work on this problem either by direct application of our proposed experimental design or serving as inspiration and motivation for other experiments.
A tool for computation of changes in Na+, K+, Cl− channels and transporters due to apoptosis by data on cell ion and water content alteration
Authors: Yurinskaya Valentina E. , Vereninov Igor A. , Vereninov Alexey A. 
Published: December 2018

AbstractThe study aims to know how the apoptotic alteration of cell ionic balance follows from the quantitatively characterised time dependent decrease in the sodium pump rate constant and changes in permeability coefficients of Cl−, K+, and Na+ channels. New experimental data on changes in cell K+, Na+, Cl−, water contents, and the Na+/ K+-ATPase-mediated K+ influx during the first 4 h of the staurosporine (STS) induced apoptosis are used as a basis for quantitative characterisation of channels and transporters responsible for apoptotic cell ion balance alteration. New computational tool is developed. It is found that the dynamics of alteration of ion and water balance in the studied U937 cells were associated with the decrease in the Na+/K+-ATPase rate coefficient by 2.2 times for 4 h, and a time-dependent increase in potassium channel permeabilitry, and a decrease in the sodium channel permeability, whereas the early decrease in [Cl−]i and cell volume were associated with an approximately 5-fold increase in the chloride channel permeability. The developed approach and the provided executable file can be used to identify the channels and transporters responsible for alterations of cell ion and water balance not only during apoptosis but in other physiological scenarios.
Change management overlooked: physician perspectives on EHR implementation
Authors: Heath Michele , Porter Tracy H. 
Published: December 2018

Purpose
The purpose of this paper is to gain understanding into the human factors which might impede the change process. Change is inevitable in contemporary organizations and particularly within the healthcare field with respect to information technology (IT). Regardless of the amount of literature surrounding change management process organizational leaders will often ignore the human factors associated with the introduction of new IT.

Design/methodology/approach
This study sought to examine physician resistance surrounding the Electronic health record (EHR) change process through the lens of each of these three aspects of the Bovey and Hede (2001a) model through semi-structured interviews with physicians. Semi-structured interviews were conducted with physicians from hospitals within the Midwest.

Findings
The findings suggest that physicians have been impacted by the EHR change management system within their hospitals. Though each of the participants experienced different issues; it was clear from the data the change to an EHR system was disruptive to their day-to-day routines and caused various challenges. EHR change management research demonstrates physicians are resisting the change despite recognizing its potential benefits.

Originality/value
This paper contributes to the change management literature by examining how physician resistance can have a negative impact on healthcare organizations during a precipitous technology change. The study also provides a unique understanding of how technology resistance can disrupt an organizational change process.
Service design for marketing in construction
Authors: Smyth Hedley , Duryan Meri , Kusuma Illona 
Published: December 2018

PurposeProject execution is dependent upon management support from the firm. The purpose of this paper is to examine the extent to which main contractors and supply chain members design their service provision in order to enhance the service experience. Marketing and service design (SD), theorized in terms of business development management, are examined to assess their effect upon service experience during project execution.Design/methodology/approachAn interpretative methodology was used to identify patterns and significant factors perceived through the lens of business development managers in ten main contractors.FindingsMain contractors provide a systems integration service, yet service provision was found to be limited and was frequently stated as “off the radar.” Clients are realizing sub-optimal value in service experience, and users and other societal stakeholders are realizing sub-optimal value in context during use.Research limitations/implicationsThere is a need to address marketing and SD research to offer prescriptive guidance to practitioners, in particular using knowledge management as lever for improvement.Social implicationsSociety is in receipt of sub-optimal facilities and therefore both socially falls short of meeting well-being and policy goals, and economically under-performs.Originality/valueContributions are made to the marketing and management theory on project markets where selling occurs ahead of provision. Scant support for construction marketing; a lack of the guidance on managing interactions in co-creating value; and the absence of SD among leading main contractors to deliver value had been reported.
The challenges of gamifying CSR communication
Authors: Maltseva Kateryna , Fieseler Christian , Trittin-Ulbrich Hannah 
Published: December 2018

PurposeA growing number of research report positive effects of gamification, that is the introduction of game elements to non-game contexts, on stakeholder intentions and behaviors. Hence, gamification is proposed as an effective tool for organizations to educate their stakeholders about corporate social responsibility (CSR) and sustainability-related topics. The paper aims to discuss these issues.Design/methodology/approachIn this paper, the authors ask whether gamification can communicate matters of social and environmental concern. Based on three consecutive experimental studies, the authors show that there are boundary conditions to the effectiveness of gamified communication on stakeholder attitude, intention and behavior.FindingsThe authors find positive, negative and insignificant effects of gamification on pro-environmental attitude, intention and behavior. Based on these ambiguous results, the authors conclude with a call for more rigorous forms of designing gamified experiences to foster stakeholder learning and highlight and develop several such future research and engagement opportunities.Originality/valueThe study is the first to apply gamification to the context of corporate and in particular CSR communication. It is furthermore one of the first studies that actually research the effects of gamification empirically, and in controlled experimental conditions.
Employee involvement and job satisfaction: a tale of the millennial generation
Authors: García Gustavo A. , Gonzales-Miranda Diego René , Gallo Oscar , Roman-Calderon Juan Pablo 
Published: December 2018

PurposeThe purpose of this paper is to empirically study the effect of employee involvement in the workplace on job satisfaction for millennial workers in Colombia.Design/methodology/approachData were obtained from a sample of 2103 millennial employees working in 11 companies of different sectors located in the five main cities of Colombia. Ordered probit models were estimated to study the effect of employee involvement on job satisfaction, in general, and how different forms of participative decision making in the workplace produce different impacts on individual satisfaction with objective and intrinsic aspects of the job, in particular.FindingsThe empirical results show that, for millennial workers, there is a positive link between employee involvement and job satisfaction. Moreover, there is a higher positive impact on job satisfaction when millennial workers participate in decisions on general aspects of the company than when they participate in specific decisions such as those concerning teamwork or main tasks at work. Another interesting result is that millennial workers attach high importance to intrinsic aspects of their jobs (such as the possibility to use their knowledge in the work), which may improve their satisfaction in a higher participative environment.Research limitations/implicationsThe results can present bias due to the use of self-report data from millennial workers. Another potential limitation is the cross-sectional nature of the data, which does not control for unobserved individual effects. The study may be extended to other developing countries to help identify results more precisely for different contexts.Originality/valueThe value lies in exploring the relationship between employee involvement and job satisfaction for millennial workers in the context of a developing country. The paper simultaneously considers different types of employee involvement and estimates their effects on different facets of job satisfaction.
The implications of fiscal decentralization and budget governance on economic capacity and community welfare
Authors: Purbadharmaja Ida Bagus Putu , Maryunani  , Ananda Candra Fajri , Santoso Dwi Budi 
Published: December 2018

Purpose
The purpose of this study is to investigate the relationship between government and Balinese society in tax decentralization through budgeting seem to insignificantly improve the welfare of Balinese society.

Design methodology/approach
This research was conducted in Bali Province involving eight regencies and one city. The data used in this study were secondary data, derived from relevant institutions or from websites through internet browsing and other documentations in the form of official reports/publications, such as regional budget, accountability reports, regional regulations and documents on budget and development of the regional economy. The present research used the partial least squares analysis technique.

Findings
Fiscal decentralization does not necessarily lead to better budget management. The success of fiscal decentralization can be found in the quality of the regional budget and the quality of budget management. The allocation of the regional budget for public service improvement and the development of infrastructure will increase the economic capacity of the regions. Improvement in regional economic capacity encourages the improvement of community welfare.

Originality/value
This income inequality points to the issue of fiscal capacity. The development of the financial role of district/city regions in the Province of Bali remains at a level gap with the development level of community welfare. During this period, the financial role of the government as estimated from the ratio of the national budget to the regional budget is higher than that of the society development. The acceleration role of the government is not proportional to the development of Human Development Index outcomes.