bluuebunny/crossref_metadata_2025_split huggingface dataset:
Windows of opportunity for Ebola virus infection treatment and vaccination
Authors: Nguyen Van Kinh , Hernandez-Vargas Esteban A. 
Published: April 2017

ABSTRACTEbola virus (EBOV) infection causes a high death toll, killing a high proportion of EBOV infected patients within 7 days. Comprehensive data on EBOV infection are very fragmented, hampering efforts in developing therapeutics and vaccines against EBOV. Under this circumstance, mathematical models become valuable resources to explore potential controlling strategies. In this paper, we employed experimental data of EBOV-infected nonhuman primates (NHPs) to construct a mathematical framework for determining windows of opportunity for treatment and vaccination. Considering a prophylactic vaccine based on recombinant vesicular stomatitis virus expressing the EBOV glycoprotein (VSV-EBOV), we found that the time window can be subject-specific, but vaccination could be protective if a subject is vaccinated during a period from one week to four months before infection. For the case of a therapeutic vaccine based on monoclonal antibodies (mAbs), a single dose might resolve the invasive EBOV replication even it was administrated as late as four days after infection. Our mathematical models can be used as building blocks for developing therapeutic and vaccine modalities as well as for evaluating public health intervention strategies in outbreaks. Future laboratory experiments will help to validate and refine the estimates of the windows of opportunity proposed here.
Non-parametric estimation of population size changes from the site frequency spectrum
Authors: Waltoft Berit Lindum , Hobolth Asger 
Published: April 2017

AbstractThe variability in population size is a key quantity for understanding the evolutionary history of a species. We present a new method, CubSFS, for estimating the changes in population size of a panmictic population from the site frequency spectrum. First, we provide a straightforward proof for the expression of the expected site frequency spectrum depending only on the population size. Our derivation is based on an eigenvalue decomposition of the instantaneous coalescent rate matrix. Second, we solve the inverse problem of determining the variability in population size from an observed SFS. Our solution is based on a cubic spline for the population size. The cubic spline is determined by minimizing the weighted average of two terms, namely (i) the goodness of fit to the SFS, and (ii) a penalty term based on the smoothness of the changes. The weight is determined by cross-validation. The new method is validated on simulated demographic histories and applied on data from nine different human populations.
A cassava drought inducible CC-type glutaredoxin,MeGRX232, negatively regulates drought tolerance inArabidopsisby inhibition of ABA-dependent stomatal closure
Authors: Ruan Meng-Bin , Yang Yi-Ling , Guo Xin , Wang Xue , Wang Bin , Yu Xiao-Ling , Zhang Peng , Peng Ming 
Published: April 2017

AbstractCC-type glutaredoxins (GRXs) are a land plant-specific GRX subgroup that evolved from CGFS GRXs, and participate in organ development and stress responses through the regulation of transcription factors. Here, genome-wide analysis identified 18 CC-type GRXs in the cassava genome, of which six (MeGRX058, 232, 360, 496, 785, and892) were induced by drought and ABA stress in cassava leaves. Furthermore, we found that overexpression ofMeGRX232results in drought hypersensitivity in soil-grown plants, with a higher water loss rate, but with increased tolerance of mannitol and ABA inArabidopsison the sealed agar plates. The ABA induced stomatal closure is impaired inMeGRX232-OE Arabidopsis. Further analysis reveals that the overexpression ofMeGRX232leads to more ROS accumulation in guard cells. MeGRX232 can interact with TGA5 fromArabidopsisand MeTGA074 from cassavain vitroandin vivo. The results of microarray assays show thatMeGRX232-OEaffected the expression of a set of drought and oxidative stress related genes. Taken together, we demonstrated that CC-type GRXs involved in ABA signal transduction and play roles in response to drought through regulating stomatal closure.Novelty statement:We found that drought and ABA stress induced the transcription of CC-type glutaredoxins (GRXs) in cassava leaves. Ectopic expression of one of them,MeGRX232inArabidopsisaffected the sensitivity to abscisic acid (ABA) and mannitol, and caused drought hypersensitivity by impairment of ABA-dependent stomatal closure.
Perturbation of PTEN-PI3K/AKT Signalling Impaired Autophagy Modulation in Dystrophin-Deficient Myoblasts
Authors: Dain Yazid Muhammad , Smith Janet 
Published: April 2017

AbstractAlteration of single protein regulation has given a massive implication in Muscular Dystrophy pathogenesis. Herein, we investigated the contribution of defected dystrophin that has impaired PI3K/Akt signalling and subsequently reduced autophagy in dystrophin-deficient myoblasts. In this study, dfd13 (dystrophin-deficient) and C2C12 (non-dystrophic) myoblasts were cultured in low mitogen condition for 10 days to induce differentiation. Analyses of protein expression has been done by using immunoblot technique, immunofluorescence and flow cytometry. In our myoblasts differentiation system, the dfd13 myoblasts did not achieved terminal differentiation as fewer myotube formation and fast-myosin heavy chain expression almost not detected. Immunoblot analysis showed that PTEN expression is profoundly increased in dfd13 myoblasts throughout the differentiation day. As a result, the PI3K activity is decreased and has caused serine/threonine kinase Akt inactivation. Both residues; Thr308 and Ser473, on Akt were found not phosphorylated. The mTOR activation by Ser2448 phosphorylation was decreased indicates an impairment for raptor and rictor binding. Unable to form complexes; mTORC1 target protein, p70S6K1 activation was found reduced at the same time explained un-phosphorylated-Akt at Ser473 by rictor-mTORC2. As one of Akt downstream protein, transcription factor FoxO3 regulation was found impaired as it was highly expressed and highly mainly localised in the nucleus in dfd13 towards the end of the differentiation day. This occurrence has caused higher activation of autophagy related genes; Beclin1, Atg5, Atg7, in dfd13 myoblasts. Autophagosome formation was increased as LC3B-I/II showed accumulation upon differentiation. However, ratio of LC3B lipidation and autophagic flux were shown decreased which exhibited dystrophic features. As a conclusion, destabilisation of plasma membrane owing to dystrophin mutation has caused the alteration of plasma membrane protein regulation particularly PTEN-PI3K, thus impaired autophagy modulation that critical for myoblasts development.
RNA helicase, DDX27 regulates skeletal muscle growth and regeneration by modulation of translational processes
Authors: Bennett Alexis H , O’Donohue Marie-Francoise , Gundry Stacey R. , Chan Aye T. , Widrick Jeffery , Draper Isabelle , Chakraborty Anirban , Zhou Yi , Zon Leonard I. , Gleizes Pierre-Emmanuel , Beggs Alan H. , Gupta Vandana A 
Published: April 2017

ABSTRACTGene expression in a tissue-specific context depends on the combined efforts of epigenetic, transcriptional and post-transcriptional processes that lead to the production of specific proteins that are important determinants of cellular identity. Ribosomes are a central component of the protein biosynthesis machinery in cells; however, their regulatory roles in the translational control of gene expression in skeletal muscle remain to be defined. In a genetic screen to identify critical regulators of myogenesis, we identified a DEAD-Box RNA helicase, DDX27, that is required for skeletal muscle growth and regeneration. We demonstrate that DDX27 regulates ribosomal RNA (rRNA) maturation, and thereby the ribosome biogenesis and the translation of specific transcripts during myogenesis. These findings provide insight into the translational regulation of gene expression in myogenesis and suggest novel functions for ribosomes in regulating gene expression in skeletal muscles.AUTHOR SUMMARYInherited skeletal muscle diseases are the most common form of genetic disorders with primary abnormalities in the structure and function of skeletal muscle resulting in the impaired locomotion in affected patients. A major hindrance to the development of effective therapies is a lack of understanding of biological processes that promote skeletal muscle growth. By performing a forward genetic screen in zebrafish we have identified mutation in a RNA helicase that leads to perturbations of ribosomal biogenesis pathway and impairs skeletal muscle growth and regeneration. Therefore, our studies have identified novel ribosome-based disease processes that may be therapeutic modulated to restore muscle function in skeletal muscle diseases.
Natural variation in a single amino acid underlies cellular responses to topoisomerase II poisons
Authors: Zdraljevic Stefan , Strand Christine , Seidel Hannah S. , Cook Daniel E. , Doench John G. , Andersen Erik C. 
Published: April 2017

ABSTRACTMany medications, including chemotherapeutics, are differentially effective from one patient to the next. Understanding the causes of these population-wide differences is a critical step towards the development of personalized treatments and improvements to existing medications. Here, we investigate natural differences in sensitivity to anti-neoplastic drugs that target topoisomerase II, using the model organismCaenorhabditis elegans. We show that wild isolates ofC. elegansvary in their sensitivity to these drugs, and we use an unbiased statistical and molecular genetics approach to demonstrate that this variation is explained by a methionine-to-glutamine substitution in topoisomerase II (TOP-2). The presence of a non-polar methionine at this residue increases hydrophobic interactions between TOP-2 and the poison etoposide, as compared to a polar glutamine. We hypothesize that this stabilizing interaction results in increased genomic instability in strains that contain a methionine residue. The residue affected by this substitution is conserved from yeast to humans and is one of the few differences between the two human topoisomerase II isoforms (methionine in hTOPIIα and glutamine in hTOPIIβ). We go on to show that this substitution influences binding and cytotoxicity of etoposide and two additional topoisomerase II poisons in human cell lines. These results explain why hTOPIIα and hTOPIIβ are differentially affected by various poisons and demonstrate the utility ofC. elegansin understanding the genetics of drug responses.
Hypothesis: Hypoxia inducesde novosynthesis of NeuGc gangliosides in humans through CMAH domain substitute
Authors: Bousquet Paula A. , Sandvik Joe Alexander , Edin Nina F. Jeppesen , Krengel Ute 
Published: April 2017

AbstractImmunotherapy is a growing field in cancer research. A privileged tumor-associated antigen that has received much attention isN-glycolyl (NeuGc) GM3. This ganglioside is present in several types of cancer, but is almost undetectable in human healthy tissues. However, its non-hydroxylated variant, NeuAc GM3, is abundant in all mammals. Due to a deletion in the human gene encoding the key enzyme for synthesis of NeuGc, humans, in contrast to other mammals, cannot synthesize NeuGc GM3. Therefore the presence of this ganglioside in human cancer cells represents an enigma. It has been shown that hypoxic conditions trigger the expression of NeuGc gangliosides, which not only serve as attractive targets for cancer therapy, but also as diagnostic and prognostic tumor marker. Here, we confirm hypoxia-induced expression of the NeuGc GM3 ganglioside also in HeLa cells and reveal several candidate proteins, in particular GM3 synthase and subunit B of respiratory complex II (SDHB), that may be involved in the generation of NeuGc GM3 by SILAC-based proteome analysis. These findings have the potential to significantly advance our understanding of how this enigmatic tumor-associated antigen is produced in humans, and also suggest a possible mechanism of action of anti-tumor antibodies that recognize hypoxia markers, such as 14F7.
An evaluation of performance arts in generating business value
Authors: Harwood Tracy , Smith Sophy 
Published: April 2017

Purpose
The purpose of this paper is to present the findings from research that explores the business value of a performance arts-based initiative in supporting change management through devising. Devising is a process that encompasses improvisation to generate social interaction within a community of practice.

Design/methodology/approach
A novel approach is reported on: a case study that includes interviews with key members of partner organizations, representing a business, a performance producer and a commissioning agency, participant observation of a member of the performance production film and the devising process.

Findings
Findings presented highlight phases of the devising process and the engagement with the creative practices employed. Findings highlight that benefits emerge through the reflexive nature of activities during the processes of creating the performance, as well as reflection on the final performance piece.

Research limitations/implications
Case study research is necessarily a qualitative design that is not generalizable to a broader population. Findings do, however, highlight potentially useful practices that may be further developed for future research.

Practical implications
Performance arts has pushed previously untested boundaries in employee engagement within the business, resulting in deep understanding between managers and employees on how value may be co-created and redeployed across the business.

Originality/value
The paper extends the application of improvisation by situating it within the creative practice of devising. This enables performance to be critically examined as an arts-based initiative within business contexts.
Functions of intermediaries in arts-based cooperations
Authors: Sandberg Berit 
Published: April 2017

PurposeArts-based cooperations between business and the arts create innovative solutions for companies by introducing artistic practices. Cooperations of this nature are predominantly prepared and implemented by intermediaries who act as “matchmakers” and bridge the cultural clash. The paper aims to discuss these issues.Design/methodology/approachFor the present study on the function of such intermediaries, qualitative data material from interviews and case studies on arts-based cooperations was collected and analysed.FindingsThis paper analyses the results from an institutional economics perspective. By drawing on transaction cost theory and information economics, the findings are transformed into an intermediation theory of arts-based cooperations. The theory postulates that intermediaries are able to reduce transaction costs as well as the risks which are contingent on asymmetric information. Involving an intermediary produces cost advantages compared to direct contact between companies and artists.Originality/valueThe analysis illuminates an important but heretofore neglected aspect of arts-based initiatives thus providing an indication for their successful implementation.
Impact and OperaScotland, the listings and archive website
Authors: Fraser Peter James , Fraser Iain Simon , Fraser Stephen 
Published: April 2017

Purpose
The purpose of this paper is to reflect on the creation of a performing arts archive website, exploring impact in relation to the marketing and promotion of opera and understanding of opera history.

Design/methodology/approach
The paper sets out a case study reflection in relation to a social enterprise in the arts.

Findings
The paper confirms that development of a specialist or niche website is a slow process requiring significant effort and resource. Promotion draws on a variety of activities including networking, face-to-face selling, word of mouth and use of new media.

Research limitations/implications
The paper summarises participant experience of launching a hobby website in the cultural sector. Constraints such as patchiness of coverage are noted together with the need for collaboration. Finally, qualitative examples of impact are identified and discussed to indicate directions for further development and research.

Practical implications
A case study offering insights and potential learning points for those considering such projects or in similar positions.

Originality/value
The project described is unique yet addresses a research problem noted by many. The paper highlights some areas for future collaboration and research both nationally and internationally.
Critical reflections on performing arts impact evaluations
Authors: Williams-Burnett Nicola Jayne , Skinner Heather 
Published: April 2017

Purpose
The purpose of this paper is to present a critically reflective account of the process of conducting an impact evaluation of a dance-theatre company’s staged productions and workshops.

Design/methodology/approach
There are two main approaches: the introspective critical reflection on the process of performing an impact evaluation; and the drawing/colouring methods used to perform it.

Findings
It is more difficult to provide impact evaluations of the soft rather than hard outcomes of publicly funded performance arts. The engagement of third-party evaluators may help overcome the challenge that many “accepted” approaches are outwith the skill or financial resources of smaller non-profit organisations.

Research limitations/implications
Although based on a single case, the authors believe that the evidence how the use of innovative methodologies may be more appropriate to performing arts impact evaluations, even those less familiar to management researchers.

Practical implications
This paper offers insights into various methods of impact evaluation that may be of use to smaller non-profit arts organisations who may be constrained by limited skills and financial resources.

Originality/value
This paper provides an original contribution to understanding innovative methodologies to perform arts impact evaluations, particularly those assessing soft outcomes, and a contribution in recognising the role of academic researchers in performing such evaluations.
What’s in a thang? Dancing to brand image with Miley Cyrus’ multimodal dance spectacle
Authors: Rossolatos George 
Published: April 2017

Purpose
The purpose of this paper is to scrutinize how Miley Cyrus’ brand values are projected through the multimodal semiotic structure of the live performance of the song Do my thang (from the Bangerz album (2013)).

Design/methodology/approach
Sociosemiotic conceptual framework in conjunction with an interpretive videographic method of analysis, facilitated by the multimodal qualitative discourse analytic software ATLAS.ti.

Findings
Four major territories were identified as regards the spectacle’s latent axiology, namely, freeplay, polymorphous sexuality, neo-burlesque, and hyperdifferentiation.

Practical implications
Attending to structural couplings between signs and modes in the context of bespoke artists’ brand languages constitutes a priority for managing an artist as brand, and, concomitantly, for safeguarding relevance for a fandom. A multimodal reading grid is offered to this end.

Originality/value
From a branding point of view, this study constitutes the first one that theorizes the live show spectacle as the manifest discourse whereupon brand image and brand values are edified, with an emphasis on the dance mode, over and above the verbal/visual modes that dominate the advertising/branding literatures.
The many faces of fear: a synthesis of the methodological variation in characterizing predation risk
Authors: Moll Remington J. , Redilla Kyle M. , Mudumba Tutilo , Muneza Arthur B. , Gray Steven M. , Abade Leandro , Hayward Matt W. , Millspaugh Joshua J. , Montgomery Robert A. 
Published: April 2017

SummaryPredators affect prey by killing them directly (lethal effects) and by inducing costly antipredator behaviours in living prey (risk effects). Risk effects can strongly influence prey populations and cascade through trophic systems. A prerequisite for assessing risk effects is characterizing the spatiotemporal variation in predation risk.Risk effects research has experienced rapid growth in the last several decades. However, preliminary assessments of the resultant literature suggest that researchers characterize predation risk using a variety of techniques. The implications of this methodological variation for inference and comparability among studies have not been well recognized or formally synthesized.We couple a literature survey with a hierarchical framework, developed from established theory, to quantify the methodological variation in characterizing risk using carnivore–ungulate systems as a case study. Via this process, we documented 244 metrics of risk from 141 studies falling into at least 13 distinct subcategories within three broader categories.Both empirical and theoretical work suggest risk and its effects on prey constitute a complex, multi‐dimensional process with expressions varying by spatiotemporal scale. Our survey suggests this multi‐scale complexity is reflected in the literature as a whole but often underappreciated in any given study, which complicates comparability among studies and leads to an overemphasis on documenting the presence of risk effects rather than their mechanisms or scale of influence.We suggest risk metrics be placed in a more concrete conceptual framework to clarify inference surrounding risk effects and their cascading effects throughout ecosystems. We recommend studies (i) take a multi‐scale approach to characterizing risk; (ii) explicitly consider ‘true’ predation risk (probability of predation per unit time); and (iii) use risk metrics that facilitate comparison among studies and the evaluation of multiple competing hypotheses. Addressing the pressing questions in risk effects research, including how, to what extent and on what scale they occur, requires leveraging the advantages of the many methods available to characterize risk while minimizing the confusion caused by variability in their application.