bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chitosan biosynthesis and virulence in the human fungal pathogenCryptococcus gattii
Authors: Lam Woei C. , Upadhya Rajendra , Specht Charles A. , Ragsdale Abigail E. , Hole Camaron R , Levitz Stuart M. , Lodge Jennifer K. 
Published: September 2019

AbstractCryptococcus gattiiR265 is a hyper-virulent fungal strain responsible for the major outbreak of cryptococcosis in Vancouver Island of British Columbia in 1999. It differs significantly fromC. neoformansin its natural environment, its preferred site in the mammalian host, and in the nature and mode of pathogenesis. Our previous studies inC. neoformanshave shown that the presence of chitosan, the deacetylated form of chitin, in the cell wall attenuates inflammatory responses in the host, while its absence induces robust immune responses, which in turn facilitate clearance of the fungus and induces a protective response. The results of the present investigation reveal that the cell wall ofC. gattiiR265 contains 2-3-fold higher amount of chitosan compared to that ofC. neoformans. The genes responsible for the biosynthesis of chitosan are highly conserved in the R265 genome; the roles of the three chitin deacetylases (CDA) have however, been modified. To deduce their roles, single, double and a tripleCDAdeletion strains were constructed in a R265 background and were subjected to mammalian infection studies. UnlikeC. neoformanswhere Cda1 has a discernible role in fungal pathogenesis, in R265 Cda3 is critical for virulence. Deletion of eitherCDA3alone (cda3Δ) or in combination with eitherCDA1(cda1Δ3Δ) orCDA2(cda2Δ3Δ) or both (cda1Δ2Δ3Δ) rendered the yeast cells avirulent and were cleared from the infected host. Moreover, thecda1Δ2Δ3Δstrain of R265 induced a protective response to a subsequent infection with R265. These studies shed more light into the regulation of chitosan biosynthesis ofC. gattiiand its subsequent effect on fungal virulence.ImportanceThe fungal cell wall is an essential organelle whose components provide the first line of defense against host-induced antifungal activity. Chitosan is one of the carbohydrate polymers in the cell wall that significantly affects the outcome of host-pathogen interaction. Chitosan-deficient strains are avirulent, implicating chitosan as a critical virulence factor.C. gattiiR265 is an important fungal pathogen of concern due to its ability to cause infections in individuals with no apparent immune dysfunction and an increasing geographical distribution. Characterization of the fungal cell wall and understanding the contribution of individual molecules of the cell wall matrix to fungal pathogenesis offers new therapeutic avenues for intervention. In this report, we show that theC. gattiiR265 strain has evolved alternate regulation of chitosan biosynthesis under both laboratory growth conditions and during mammalian infection compared to that ofC. neoformans.
Inhibition of tRNA Synthetases Induces Persistence inChlamydia
Authors: Hatch Nathan D. , Ouellette Scot P. 
Published: September 2019

AbstractChlamydia trachomatisis the leading cause of bacterial sexually transmitted infections, andC. pneumoniaecauses community-acquired respiratory infections.In vivo, the host immune system will release interferon-gamma (IFNγ) to combat infection. IFNγ activates human cells to produce the tryptophan (trp) catabolizing enzyme, IDO. Consequently, there is a reduction in cytosolic trp in IFNγ-activated host cells. In evolving to obligate intracellular dependence,Chlamydiahas significantly reduced its genome size and content as it relies on the host cell for various nutrients. Importantly,C. trachomatisandC. pneumoniaeare trp auxotrophs and are starved for this essential nutrient when the human host cell is exposed to IFNγ. To survive this, chlamydiae enter an alternative growth state referred to as persistence. Chlamydial persistence is characterized by a halt in the division cycle, aberrant morphology, and, in the case of IFNγ-induced persistence, trp codon-dependent changes in transcription. We hypothesize that these changes in transcription are dependent on the particular amino acid starvation state. To investigate the chlamydial response mechanisms acting when other amino acids become limiting, we tested the efficacy of prokaryotic specific tRNA synthetase inhibitors, indolmycin and AN3365, to mimic starvation of trp and leucine, respectively. We show that these drugs block chlamydial growth and induce changes in morphology and transcription consistent with persistence. Importantly, growth inhibition was reversed when the compounds were removed from the medium. With these data, we find that indolmycin and AN3365 are valid tools that can be used to mimic the persistent state independently of IFNγ.ImportanceThe obligate intracellular pathogenChlamydia trachomatis, although treatable, remains a major public health concern due to rising infection rates. The asymptomatic nature of mostChlamydiainfections is hypothesized to be a product of its ability to transition into a slow-growing state referred to as persistence. The most physiologically relevant inducer of persistence is the immune cytokine IFNγ, which in humans activates an enzyme that degrades tryptophan, an essential amino acid thatChlamydiascavenges from the host cell. Unfortunately, the exact timing at whichChlamydiais starved after IFNγ treatment is inexact. To mechanistically study persistence using genetic tools, an experimental model where amino acid starvation can be induced at specific times is needed. Here, we demonstrate the capability of tRNA synthetase inhibitors, indolmycin and AN3365, to model persistence independently from the use of IFNγ. These tools will also allow comparisons between amino acid stress responses in this unique bacterium.
AR phosphorylation and CHK2 kinase activity regulates IR stabilized AR – CHK2 interaction and prostate cancer survival
Authors: Ta Huy Q , Dworak Natalia , Ivey Melissa L , Roller Devin G. , Gioeli Daniel 
Published: September 2019

ABSTRACTWe have previously demonstrated that checkpoint kinase 2 (CHK2) is a critical negative regulator of androgen receptor (AR) transcriptional activity, prostate cancer (PCa) cell growth, and androgen sensitivity. We have now uncovered that the AR directly interacts with CHK2 and ionizing radiation (IR) increases this interaction. This IR-induced increase in AR–CHK2 interactions requires AR phosphorylation and CHK2 kinase activity. PCa associated CHK2 mutants with impaired kinase activity reduced IR-induced AR–CHK2 interactions. The destabilization of AR–CHK2 interactions induced by CHK2 variants impairs CHK2 negative regulation of cell growth. CHK2 depletion increases transcription of DNAPK and RAD54, increases clonogenic survival, and increases resolution of DNA double strand breaks. The data support a model where CHK2 sequesters the AR through direct binding decreasing AR transcription and suppressing PCa cell growth. CHK2 mutation or loss of expression thereby leads to increased AR transcriptional activity and survival in response to DNA damage.
Growth-regulated Hsp70 phosphorylation regulates stress responses and prion maintenance
Authors: Kao Chung-Hsuan , Ryu Seung , Kim Min J. , Wen Xuemei , Wimalarathne Oshadi , Paull Tanya T. 
Published: September 2019

AbstractMaintenance of protein homeostasis in eukaryotes during normal growth and stress conditions requires the functions of Hsp70 chaperones and associated co-chaperones. Here we investigate an evolutionarily-conserved serine phosphorylation that occurs at the site of communication between the nucleotide-binding and substrate-binding domains of Hsp70. Ser151 phosphorylation in yeast Hsp70 (Ssa1) is promoted by cyclin-dependent kinase (Cdk1) during normal growth and dramatically affects heat shock responses, a function conserved with Hsc70 S153 phosphorylation in human cells. Phospho-mimic forms of Ssa1 (S151D) also fail to relocalize in response to starvation conditions, do not associatein vivowith Hsp40 co-chaperones, Ydj1 and Sis1, and do not catalyze refolding of denatured proteinsin vitroin cooperation with Ydj1 and Hsp104. S151 phosphorylation strongly promotes survival of heavy metal exposure and reduces Sup35-dependent[PSI+]prion activity, however, consistent with proposed roles for Ssa1 and Hsp104 in generating self-nucleating seeds of misfolded proteins. Taken together, these results suggest that Cdk1 downregulates Hsp70 function during periods of active growth, reducing propagation of aggregated proteins despite potential costs to overall chaperone efficiency.
Detection of ctDNA from dried blood spots after DNA size selection
Authors: Heider Katrin , Wan Jonathan C. M. , Hall James , Boyle Samantha , Hudecova Irena , Gale Davina , Cooper Wendy N. , Corrie Pippa G. , Brenton James D. , Smith Christopher G. , Rosenfeld Nitzan 
Published: September 2019

AbstractRecent advances in the research and clinical applications of circulating tumour DNA (ctDNA) is limited by practical considerations of sample collection. Whole genome sequencing (WGS) is increasingly used for analysis of ctDNA, identifying copy-number alterations, fragment size patterns, and other genomic features. We hypothesised that low-depth WGS data may be generated from minute amounts of cell-free DNA, and that fragment-size selection may be effective to remove contaminating genomic DNA (gDNA) from small volumes of blood. There are practical advantages to using dried blood spots as these are easier to collect, facilitate serial sampling, and support novel study designs in prospective human studies, animal models and expand the utilisation of archival samples by the removal of gDNA in small volumes. We therefore developed a protocol for the isolation and analysis of cell-free DNA from dried blood spots. Analysing a dried blood spot of 50μL frozen whole blood from a patient with melanoma, we identified ctDNA based on tumour-specific somatic copy-number alterations, and found a fragment size profile similar to that observed in plasma DNA processed by traditional methods. We extended this approach to detect tumour-derived cell-free DNA in a dried blood spot from a mouse xenograft model and were able to identify ctDNA from the originally grafted ascites. Together, our data suggests that ctDNA can be detected and monitored in dried blood spots. This will enable new approaches for sample collection from patients andin vivomodels.
“Mainstreaming” foresight program development in the public sector
Authors: Janzwood Scott , Piereder Jinelle 
Published: September 2019

Purpose
This paper aims to develop a framework for benchmarking the maturity of public sector foresight programs and outlines strategies that program managers can use to overcome obstacles to foresight program development in government.

Design/methodology/approach
The public sector foresight benchmarking framework is informed by a bibliometric analysis and comprehensive review of the literature on public sector foresight, as well as three rounds of semi-structured interviews conducted over the course of a collaborative 18-month project with a relatively young department-level foresight program at the government of an Organisation for Economic Co-operation and Development (OECD) country. The paper frames public sector organizations as “complex adaptive systems” and draws from other government initiatives that require fundamental organizational change, namely, “gender mainstreaming”.

Findings
Nascent or less mature programs tend to be output-focused and disconnected from the policy cycle, while more mature programs balance outputs and participation as they intervene strategically in the policy cycle. Foresight program development requires that managers simultaneously pursue change at three levels: technical, structural and cultural. Therefore, successful strategies are multi-dimensional, incremental and iterative.

Originality/value
The paper addresses two important gaps in the literature on public sector foresight programs by comprehensively describing the key attributes of mature and immature public sector foresight programs, and providing flexible, practical strategies for program development. The paper also pushes the boundaries of thinking about foresight by integrating insights from complexity theory and complexity-informed organizational change theory.
Delphi method: analysis of rounds, stakeholder and statistical indicators
Authors: Zartha Sossa Jhon Wilder , Halal William , Hernandez Zarta Raul 
Published: September 2019

PurposeThe purpose of this study is to review the literature on the Delphi method, its characteristics and current applications through an analysis of recent most-cited scientific papers, with an emphasis on three axes, namely, the number of rounds used, stakeholder participation relevance or only academic experts’ participation and the possibility of using indicators or techniques different from those related to descriptive statistics.Design/methodology/approachIn total, 57 papers were initially reviewed, 10 of them with a high citation rate. Then, an analysis was made of papers in Scopus for the period 2015-2018 published in theTechnological Forecasting and Social Change Journaland inthe Futures and Foresight Journal, which had the characteristic of displaying quartileQ1orQ2in Scimago in addition to being in Scopus.FindingsAmong the main results, the authors observe the tendency to use fewer rounds, a higher prevalence of stakeholder participation and not only academic experts but also the use of new types of modified Delphi such as real-time spatial Delphi, Delphi group, market Delphi, real-world Delphi and policy Delphi.Originality/valueAmong the conclusions, the possibility of using other indicators or complementary techniques to the descriptive statistics is highlighted such as number of justifications or comments between rounds, coefficients to quantify the competence or degree of expertise of the participants, measures of the perception of the expert on the usefulness of the presented feedback, graphs of the number of arguments according to the number of questions, the Wilcoxon Ranked Pairs Test, the k means, Kolmogorov–Simonov test and the Mann–Whitney U-test.
Roma populations and health inequalities: a new perspective
Authors: Orton Lois , Anderson de Cuevas Rachel , Stojanovski Kristefer , Gamella Juan F. , Greenfields Margaret , La Parra Daniel , Marcu Oana , Matras Yaron , Donert Celia , Frost Diane , Robinson Jude , Rosenhaft Eve , Salway Sarah , Sheard Sally , Such Elizabeth , Taylor-Robinson David , Whitehead Margaret 
Published: September 2019

Purpose
The purpose of this paper is to explore the emergence of “Roma health and wellbeing” as a focus of attention in European research and in policy and the possible detrimental consequences of action founded on a generic representation of “Roma health.”

Design/methodology/approach
Based on discussions with and research conducted by scholars who work directly with Roma communities across European regions from a wide range of academic disciplines it suggests how future research might inform: a more nuanced understanding of the causes of poor health and wellbeing among diverse Roma populations and; actions that may have greater potential to improve the health and wellbeing among these populations.

Findings
In summary, the authors promote three types of research: first critical analyses that unpick the implications of current and past representations of “Roma” and “Roma health.” Second, applied participatory research that meaningfully involves people from specific self-defined Roma populations to identify important issues for their health and wellbeing. Third, learning about processes that might impact on the health and wellbeing of Roma populations from research with other populations in similarly excluded situations.

Originality/value
The authors provide a multidisciplinary perspective to inform research that does not perpetuate further alienation and prejudice, but promotes urgent action to redress the social and health injustices experienced by diverse Roma populations across Europe.
Social media effects?
Authors: Moon Miri , Shim Jae-chul 
Published: September 2019

Purpose
The purpose of this paper is to examine the relationships among media exposure, general scientific knowledge and the public’s risk perceptions of bovine spongiform encephalopathy (BSE).

Design/methodology/approach
Data for this study are based on a survey of 1,001 South Korean adult consumers (502 females and 499 males). The data were analyzed using SPSS 17.0, and multiple linear regression was performed to examine the relationships between risk perceptions and the types of media channel exposure, as well as between risk perceptions and general scientific knowledge.

Findings
Results showed that among the measured socio-demographic characteristics, gender was a significant factor. With regard to the variability of media exposure, individuals who were exposed to more internet news were found to have higher risk perceptions in terms of how BSE could affect themselves, while respondents who were more exposed to social networking sites (SNSs) were concerned about how the disease could affect others.

Originality/value
This study provides additional evidence of the third-person effect in risk perceptions of BSE, filling scientific knowledge gaps. Hence, this study suggests that the types of media channels (internet news, television and SNSs) should be considered as significant predictors of risk perceptions about food hazards related to the health of the consumer and others.
Strategy and organisational cybersecurity: a knowledge-problem perspective
Authors: Sallos Mark Paul , Garcia-Perez Alexeis , Bedford Denise , Orlando Beatrice 
Published: September 2019

Purpose
The purpose of this paper is to frame organisational cybersecurity through a strategic lens, as a function of an interplay of pragmatism, inference, holism and adaptation. The authors address the hostile epistemic climate for intellectual capital management presented by the dynamics of cybersecurity as a phenomenon. The drivers of this hostility are identified and their implications for research and practice are discussed.

Design/methodology/approach
The philosophical foundations of cybersecurity in its relation with strategy, knowledge and intellectual capital are explored through a review of the literature as a mechanism to contribute to the emerging theoretical underpinnings of the cybersecurity domain.

Findings
This conceptual paper argues that a knowledge-based perspective can serve as the necessary platform for a phenomenon-based view of organisational cybersecurity, given its multi-disciplinary nature.

Research limitations/implications
By recognising the knowledge-related vectors, mechanisms and tendencies at play, a novel perspective on the topic can be developed: cybersecurity as a “knowledge problem”. In order to facilitate such a perspective, the paper proposes an emergent epistemology, rooted in systems thinking and pragmatism.

Practical implications
In practice, the knowledge-problem narrative can underpin the development of new organisational support constructs and systems. These can address the distinctiveness of the strategic challenges that cybersecurity poses for the growing operational reliance on intellectual capital.

Originality/value
The research narrative presents a novel knowledge-based analysis of organisational cybersecurity, with significant implications for both interdisciplinary research in the field, and practice.
The moderating effect of firm size on relational capital and firm performance
Authors: Corvino Antonio , Caputo Francesco , Pironti Marco , Doni Federica , Bianchi Martini Silvio 
Published: September 2019

PurposeThe purpose of this paper is to contribute to the ongoing debate regarding the relationship between relational capital (RC) and firm performance, by investigating the moderation effect of firm size and its key role in defining conditions for competitive advantage.Design/methodology/approachThe paper uses the interpretative lens of the resource dependence theory, and refreshes consolidated studies rooted in RC. It identifies a set of variables to measure the influence of RC on firm performance, including the cost of goods sold, interest expenses and earnings per share. Content analysis was used to capture specific features of corporate disclosure tools using 51 items pertinent to RC. The authors used a specific disclosure index drawing on data collected from 73 listed firms in France, Germany, Italy and the UK. Data covering the period from 2011 to 2013 were analyzed using six regression models.FindingsFirm size has a moderating effect on the relationship between RC and some variables linked to firm performance.Originality/valueThe study combines an internal and external perspective to investigate the interplay between firms and market environments, and therefore, enriches the ongoing debate concerning the relationship between RC and firm performance. It outlines possible ways through which RC can become an effective source of competitive advantage.
Intellectual capital and the firm: evolution and research trends
Authors: Martín-de Castro Gregorio , Díez-Vial Isabel , Delgado-Verde Miriam 
Published: September 2019

PurposeThe phenomenon of intellectual capital in the firm has been deeply researched and immensely debated in the management literature in recent years. After three decades of evolution, it has become established as a mature field of research. At this point, a review of its theoretical foundations and current and future evolution provides us with the state of the art of intellectual capital in the firm. The purpose of this paper is to present a quantitative review of the existing literature on intellectual capital in the firm.Design/methodology/approachIn this paper, the authors present a quantitative review of the existing literature on intellectual capital in the firm. To do so, the authors searched the JCR-SSCI database from 1990 to 2016 and identified 553 citing documents; these were split into three main periods in order to identify the interactions and path dependencies existing between different foundations of research. In addition, areas of current and future research connected with the theoretical foundations were identified. For these purposes, the authors used both co-citation analyses as well as bibliographical coupling.FindingsIn this paper, three main stages of IC evolution have been identified with the main topics and research frames, as well as their path dependencies. Additionally, four main areas of current and future development of IC have been identified: IC measurement, IC in new business models, IC disclosure, and its role in social capital and human resource practices.Research limitations/implicationsThe present bibliometric study is a quantitative review of papers published in the Web of Science database.Originality/valueBy its dimensions ‒ broad academic disciplines and longitudinal character ‒ this bibliometric study constitutes a new quantitative review of the IC discipline, both drawing its intellectual evolution in the last decades, and showing current and future research trends in IC and the firm.