bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative genomics for the elucidation of multidrug resistance (MDR) inCandida lusitaniae
Authors: Kannan Abhilash , Asner Sandra A. , Trachsel Emilie , Kelly Steve , Parker Josie , Sanglard Dominique 
Published: September 2019

AbstractMultidrug resistance (MDR) has emerged in hospitals due to the use of several agents administered in combination or sequentially to the same individual. We reported earlier MDR inCandida lusitaniaeduring therapy with amphotericin B (AmB), azoles and candins. We used here comparative genomic approaches between the initial susceptible isolate and 4 other isolates with different MDR profiles. From a total of 18 non-synonymous SNPs (NSS) in genome comparisons with the initial isolate, six could be associated with MDR. One of the SNPs occurred in a putative transcriptional activator (MRR1) resulting in a V668G substitution in isolates resistant to azoles and 5-fluorocytosine (5-FC). We demonstrated by gene editing thatMMR1acted by upregulation ofMFS7(a multidrug transporter) in the presence of the V668G substitution.MFS7itself mediated not only azole resistance but also 5-FC resistance, which represents a novel resistance mechanism for this drug class. Three other distinct NSS occurred inFKS1(a glucan synthase that is targeted by candins) in three candin-resistant isolates. Lastly, two other NSS inERG3andERG4(ergosterol biosynthesis) resulting in non-sense mutations were revealed in AmB-resistant isolates, one of which accumulated the 2ERGNSS. AmB-resistant isolates lacked ergosterol and exhibited sterol profiles consistent withERG3andERG4defects. In conclusion, this genome analysis combined with genetics and metabolomics helped to decipher the resistance profiles identified in this clinical case. MDR isolates accumulated 6 different mutations conferring resistance to all antifungal agents used in medicine. This case study illustrates the capacity ofC. lusitaniaeto rapidly adapt under drug pressure within the host.ImportanceAntifungal resistance is an inevitable phenomenon when fungal pathogens get exposed to antifungal drugs. These drugs can be grouped in 4 distinct classes (azoles, candins, polyenes, pyrimidine analogs) and are used in different clinical settings. Failures in therapy implicates the sequential or combined use of these different drug classes, which can result in some cases in the development of multidrug resistance (MDR). MDR is particularly challenging in the clinic since it drastically reduces possible treatment alternatives. In this study, we report the rapid development of MDR inCandida lusitaniaein a patient, which became resistant to all known antifungal agents used up to now in medicine. To understand how MDR developed inC. lusitaniae, whole genome sequencing followed by comparative genome analysis was undertaken in sequential MDR isolates. This helped to detect all specific mutations linked to drug resistance and explained the different MDR patterns exhibited by the clinical isolates.
Strain-dependent impact of G and SH deletions provide new insights for live-attenuated HMPV vaccine development
Authors: Dubois Julia , Pizzorno Andrés , Cavanagh Marie-Hélène , Padey Blandine , de Lamballerie Claire Nicolas , Uyar Olus , Venable Marie-Christine , Carbonneau Julie , Traversier Aurélien , Julien Thomas , Couture Christian , Lina Bruno , Hamelin Marie-Ève , Terrier Olivier , Rosa-Calatrava Manuel , Boivin Guy 
Published: September 2019

AbstractHuman metapneumovirus (HMPV) is a major pediatric respiratory pathogen with currently no specific treatment or licensed vaccine. Different strategies to prevent this infection have been evaluated, including live-attenuated vaccines (LAV) based on SH and/or G protein deletions. This approach showed promising outcomes but has not been evaluated further using different viral strains. In that regard, we previously showed that different HMPV strains harbor distinct in vitro fusogenic and in vivo pathogenic phenotypes, possibly influencing the selection of vaccine strains. In this study, we investigated the putative contribution of the low conserved SH or G accessory proteins in such strain-dependent phenotypes and generated recombinant wild type (WT) and SH- or G-deleted viruses derived from two different patient-derived HMPV strains, A1/C-85473 and B2/CAN98-75.The ΔSH and ΔG deletions led to different strain-specific phenotypes in both LLC-MK2 cell and reconstituted human airway epithelium models. More interestingly, the ΔG-85473 and especially ΔSH-C-85473 recombinant viruses conferred significant protection against HMPV challenge and induced immunogenicity against a heterologous strain. In conclusion, our results show that the viral genetic backbone should be considered in the design of live-attenuated HMPV vaccines, and that a SH-deleted virus based on the A1/C-85473 HMPV strain could be a promising LAV candidate as it is both attenuated and protective in mice while being efficiently produced in a cell-based system.
Evidence of adaptive host and vector manipulation by plant viruses revealed through combined meta-analysis and modeling approaches
Authors: Chesnais Quentin , Bahlai Christie A. , Peace Angela , Crowder David W. , Bosque-Pérez Nilsa A. , Mauck Kerry 
Published: September 2019

AbstractA growing number of studies indicate that plant viruses enhance their own transmission by modifying host phenotypes and vector behavior, leading to the hypothesis that such effects are manipulations resulting from virus adaptations. However, few studies have linked putative manipulations with virus components, and the true frequency and magnitude of host and vector manipulation across virus taxa remains unknown. To address this knowledge gap, we performed a meta-analysis to quantify convergence in virus effects on hosts and vectors across taxonomic groups that share transmission mechanism traits, and thereby stand to benefit from similar sequences of vector behavior. We then combined meta-analysis outputs with an epidemiological model to assess consequences of manipulation for virus spread. Overall, transmission mechanism traits strongly predicted the magnitude and nature of virus effects on vector preferences and performance. Models parameterized with meta-analysis data demonstrate that manipulation effects enhance virus spread, and that viruses with long acquisition times and retention durations are under strong selection pressure to manipulate transmission. By combining meta-analysis with epidemiological modeling, our results confirm that host and vector manipulation are important aspects of plant virus ecology and evolution while emphasizing the need to incorporate more pathosystems and transmission mechanism traits in future studies.
Persistent Cyfip1 expression is required to maintain the adult subventricular zone neurogenic niche
Authors: Habela Christa Whelan , Yoon Ki-Jun , Kim Namshik , Taga Arens , Bell Kassidy , Bergles Dwight E. , Maragakis Nicholas J. , Ming Guo-li , Song Hongjun 
Published: September 2019

ABSTRACTNeural stem cells (NSCs) persist throughout life in the subventricular zone (SVZ) niche of the lateral ventricles as B1 cells. Maintaining this population of NSCs depends on the balance between quiescence and self-renewing or self-depleting proliferation. Interactions between B1 cells and the surrounding niche are important in regulating this balance, but the mechanisms governing these processes have not been fully elucidated in adult mammals. The cytoplasmic FMRP-interacting protein (CYFIP1) regulates apical-basal polarity in the embryonic brain. Loss of Cyfip1 during embryonic development in mice disrupts the embryonic niche and affects cortical neurogenesis. However, a direct role for Cyfip1 in the regulation of adult NSCs has not been established. Here, we demonstrate that Cyfip1 expression is preferentially localized to B1 cells in the adult SVZ. Loss of Cyfip1 in the embryonic mouse brain results in altered adult SVZ architecture and expansion of the adult B1 cell population at the ventricular surface. Furthermore, acute deletion ofCyfip1in adult NSCs results in a rapid change in adherens junction proteins as well as increased proliferation and the number of B1 cells at the ventricular surface. Together, these data indicate that CYFIP1 plays a critical role in the formation and maintenance of the adult SVZ niche and, furthermore, deletion of Cyfip1 unleashes the capacity of adult B1 cells for symmetric renewal to increase the adult NSC pool.SIGNIFICANCENeural stem cells (NSCs) persist in the subventricular zone (SVZ) of the lateral ventricles in adult mammals and their population is determined by the balance between quiescence and self-depleting or renewing cell division. The mechanisms regulating their biology are not fully understood. This study establishes that the cytoplasmic FMRP interacting protein 1 (Cyfip1) regulates NSC fate decisions in the adult SVZ and NSCs that are quiescent or typically undergo self-depleting divisions retain the ability to self-renew in the adult. This contributes to our understanding of how adult NSCs are regulated throughout life and has potential implications for human brain disorders.
Information asymmetry, third party certification and the integration of organic food value chain in China
Authors: Zhao Jiang , Gerasimova Ksenia , Peng Yala , Sheng Jiping 
Published: September 2019

PurposeThe purpose of this paper is to discuss characteristics of organic food value chain governance and policy tools that can increase the supply of good quality of agri-products.Design/methodology/approachThis paper discusses a national organic food supply system in China, identifying the link between an organization form with a social confidence crisis and information asymmetry as the main challenges. It develops an analytical model of the market structure of organic certification based on the contract theory, which considers the certification incentive driven by both farmers and processors. Two cases of raw milk producers and processors provide empirical data.FindingsThe argument which is brought forward is that product information asymmetry together with strict requirement for ensuring organic food integrity brings the organic milk value chain into a highly integrated organization pattern. A tight value chain is effective in the governance of organic food supply chain under third party certification (TPC), while a loose value chain discourages producing organic products because of transaction costs. TPC is found to be a positively correlation with a tight value chain, but it brings high organizational cost and it raises cost for consumers.Originality/valueThis is the first paper discussing the governance of organic food value chain in Chinese milk industry.
Capital market penalties to radical and incremental innovation
Authors: Hain Daniel Stefan , Lindgaard Christensen Jesper 
Published: September 2019

Purpose
The purpose of this paper is to investigate how access to financing for incremental as well as radical innovation activities is affected by firm-specific structural and behavioral characteristics.

Design/methodology/approach
Deploying a two-stage Heckman probit model on survey data spanning the period 2000–2013 and covering 1,169 firms, this paper analyzes the effect of a firm’s engagement in incremental and radical innovation on its likelihood to get constrained in their access to external finance, and how this effect is moderated by the firm’s age and size.

Findings
In line with earlier research, it is confirmed that the type of innovation matters for the access to external finance, but in a more nuanced way than generally portrayed. While incremental innovation activities have little negative effect on the access to external finance, radical innovation activities tend to be penalized by capital markets. This effect appears to be particularly strong for small firms.

Originality/value
This paper provides nuanced insights into the interplay between types of firm-level innovation activities, structural characteristic and access to external finance.
A new typology to characterize Italian digital entrepreneurs
Authors: Ammirato Salvatore , Sofo Francesco , Felicetti Alberto Michele , Helander Nina , Aramo-Immonen Heli 
Published: September 2019

Purpose
Strong agreement in the extant business literature emphasizes that digital developments are key to economic growth internationally. This is in spite of the recorded high levels (up to 50 percent) of failure among digital companies and entrepreneurs. The purpose of this paper is to identify the digital debates in Italy, explore current policies and develop a typology that characterizes digital entrepreneurs (DEs) and their start-up companies in Italy.

Design/methodology/approach
The digital debates and policies are explored through an extensive telephone survey of the self-perceptions and identified supports required by 348 Italian active DEs. Quantitative statistical techniques were used including factor analysis, cluster analysis and ANOVA, to identify motivations, profiles and critical success factors relevant to the sample.

Findings
The study identifies three main clusters among the DEs: emerging very young; emerging business focused and experienced. These clusters vary with the entrepreneurs’ background and competence base, motivation and satisfaction factors. The different kinds of profiles require specific kinds of supporting policies identified by the sample that focus on financial, educational and/or networking provision.

Originality/value
The paper affirms the central role of digital entities in modern economies expressed in the current literature and increases knowledge of the perceived success factors identified by DEs. The identification and classification of self-reported characteristics of Italian DEs and to what extent these characterizations might be useful for tailored interventions to support their success are the main contributions of this study. Accordingly, an authentic, original and self-reported portrayal has been constructed of the self-perceptions of Italian DEs. Finally, the study explores the implications for actions and new policies considering self-perceived profiles, needs and expectations of DEs.
Assignment of project team members to projects
Authors: Sankaran Shankar , Vaagaasar Anne Live , Bekker Michiel Christian 
Published: September 2019

PurposeThe purpose of this paper is to investigate how project managers, influence the assignment of project team members by directly assigning or specifying who they want or by indirectly using lateral influence strategies to secure the appropriate resources. This study is part of a wider study investigating the balance between vertical and horizontal leadership in projects in which nomination (or assignment) was identified as a key event contributing to balancing the leadership. It focuses specifically on the nomination or assignment event at the start of a project.Design/methodology/approachBased on the philosophy of critical realism, case studies were used to collect data through 70 semi-structured interviews in Australia, Scandinavia and South Africa. Interviews were conducted with senior managers, project managers and project team members. Two project team members who worked with the same project manager were interviewed to gather diverse views. The data were analyzed individually by researchers from each location using a coding method proposed by Mileset al.(2014). The researchers then jointly analyzed the findings to arrive at five common themes from that explained how team members were assigned in practice.FindingsDespite the recognized need for project managers to form their own teams, this study found that project team members were often assigned by others. This was because project managers lacked authority to secure their resources. Therefore, they used lateral influence strategies to help with assigning project team members. The study identified five lateral influencing strategies adopted by project managers to assign team members: creating an image of competence; creating coalitions; taking a gamble; waiting for the right moment; and reasoning with facts. Two of these lateral influencing strategies were not identified in the previous literature on influencing strategies used in organizations.Research limitations/implicationsThe findings should not be viewed as representative of the respective continents where the cases were studied. However, this study contributes to the literature on project management, illuminating how project teams are assigned and by whom and, specifically, the role that influence plays during this event of the balanced leadership theory. It also identifies the types of lateral influence strategies used by project managers when assigning team members to their projects. It provides a pathway to explore the use of lateral influencing strategies by project managers beyond the assignment process.Practical implicationsThis study will help project managers to become aware of influencing strategies that they can use in practice while assigning team members to their projects. It will also highlight the importance of assigning the right resources to projects with a view to achieving balanced leadership.Originality/valueThis research is of value to organizations using projects to successfully deliver their strategies by assigning suitable resources to their projects.
Does trade interdependency lead linkages between stock markets? A case of South Asian countries
Authors: Kumar Rakesh 
Published: September 2019

PurposeThe purpose of this paper is to test the dynamic linkages among the stock markets of four South Asian countries (India, Pakistan, Bangladesh and Sri Lanka) in the backdrop of trade interdependency.Design/methodology/approachListed indices are used to serve the proxy of stock markets of four countries for the period: January 2000–December 2018. The study uses the autoregressive distributed lag model and Granger causality techniques in multivariate frameworks while focusing on intraregional trade as an exogenous factor for testing the long- and short-run causality in the given data set, hence raising the quality of statistical inference.FindingsThe results highlight that India and Pakistan are net exporters to the South Asian region, while Bangladesh and Sri Lanka are net importers from the region. While testing the stock markets linkages, the expanded intraregional trade volumes (exports plus imports) have occurred with the significant cointegration of stock markets of India and Pakistan with the other stock markets in the long run. In the short run, the stock markets of India, Pakistan and Sri Lanka report bidirectional causality without having significant spillovers of intraregional trade on the stock prices.Research limitations/implicationsThe study relies on the multivariate techniques with stock prices and regional trade share as the exogenous variables. Further the regulatory, political and economic conditions of sample countries are fundamentally different which in turn affect their degree of trade interdependency and integration between the stock markets.Practical implicationsNonsignificant cointegration of the stock markets of Sri Lanka and Bangladesh highlights the possibility of portfolio diversification in the long run, while the significant bidirectional causalities between the stock markets highlight the lesser degree of portfolio diversifications in the short run.Originality/valuePioneer efforts are made to examine the dynamic linkages between the South Asian stock markets while focusing on regional trade interdependency. The results provide new insight in the dynamics of stock returns of South Asian stock markets in the backdrop of intraregional trade.
The importance of university, students and students’ union partnerships in student-led projects
Authors: Briggs Sarah Jayne , Robinson Zoe P. , Hadley Rachel Louise , Laycock Pedersen Rebecca 
Published: September 2019

Purpose
This paper aims to explore a single-institution case study of partnership working between students, the University and Students’ Union, through four student-led sustainability projects. The paper analyses the role and value of these partnerships and provides advice for other institutions on effective partnership working between these stakeholders.

Design/methodology/approach
A single case study of partnership working with multiple embedded units of analysis (four projects) is presented based on reflections of practitioners involved in the projects who have different roles within the University and Students’ Union.

Findings
The longevity and effectiveness of student-led projects, and disciplinary-breadth of students engaged, can be enhanced by greater collaboration with, and integration into, University and Students’ Union systems. Partnership working between different stakeholders is key to overcoming challenges and the success of student-led projects, helped by key staff “enablers”. These projects provide myriad learning opportunities for developing change agency skills, even where projects are relatively short-lived and could be seen as failures in terms of longevity.

Research limitations/implications
This analysis is based solely on practitioner reflections, with limited direct quantification or qualitative data on the projects’ impacts on the students themselves.

Originality/value
This paper draws together the experiences and reflections of four practitioners with different roles within the University and Students’ Union across four different projects and provides advice to generate student-led sustainability projects which have longevity and impact for wider student populations and future generations of cohorts.
Intercollegiate athletic programs, university brand equity and student satisfaction
Authors: Hanson Thomas A. , Bryant Michael R. , Lyman Katie J. 
Published: September 2019

Purpose
The purpose of this paper is to explore relationships among three primary variables: sports spectatorship of intercollegiate football, university brand equity and student satisfaction. The primary purpose is to understand the extent to which athletic programs influence campus culture, sense of community and the satisfaction of undergraduate students. A secondary purpose is to probe the factor structure, reliability and validity of a recently developed sports spectatorship scale.

Design/methodology/approach
The authors collected data through an online survey of 419 undergraduate students enrolled at three separate Midwestern universities, using previously developed and validated survey scales.

Findings
Relationships between brand equity and student satisfaction suggest that athletic programs provide a benefit to universities by improving students’ psychological sense of community and emotional connection to the institution. Furthermore, correlations between sports spectatorship and brand equity measures suggest an internal advertising effect.

Originality/value
The results contribute to the understanding of the role of intercollegiate athletic programs, in this case from the perspective of enrolled undergraduate students. Additionally, the findings recommend ways that universities might maximize some of the benefits by emphasizing the emotional connection of the student body to the teams. The paper also contributes to the validation of the sports spectatorship scale as a tool for further research.