bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting aberrant DNA methylation in mesenchymal stromal cells as a treatment for myeloma bone disease
Authors: Garcia-Gomez Antonio , Li Tianlu , Rodríguez-Ubreva Javier , Ciudad Laura , Català-Moll Francesc , Martín-Sánchez Montserrat , San-Segundo Laura , Morales Xabier , Ortiz de Solórzano Carlos , Oyarzabal Julen , San José-Enériz Edurne , Agirre Xabier , Prosper Felipe , Garayoa Mercedes , Ballestar Esteban 
Published: September 2019

ABSTRACTMultiple myeloma (MM) progression and myeloma-associated bone disease (MBD) are highly dependent on the bone marrow (BM) microenvironment, in particular on mesenchymal stromal cells (MSCs). MSCs from MM patients exhibit an abnormal transcriptional profile, suggesting that epigenetic alterations could be governing the tumor-promoting functions of MSCs and their prolonged osteoblast (OB) suppression in MM. In this study, we analyzed the DNA methylome of BM-derived MSCs from patients with monoclonal gammopathy of undetermined significance, smoldering myeloma and symptomatic MM at diagnosis in comparison with their normal counterparts. DNA methylation alterations were found at each of the myeloma stage in association with deregulated expression levels of Homeobox genes involved in osteogenic differentiation. Moreover, these DNA methylation changes were recapitulatedin vitroby exposing MSCs from healthy individuals to MM plasma cells. Pharmacological targeting of DNMTs and G9a with the dual inhibitor CM-272, reverted the expression of aberrantly methylated osteogenic regulators and promoted OB differentiation of MSCs from myeloma patients. Most importantly, in a mouse model of bone marrow-disseminated MM, administration of CM-272 prevented tumor-associated bone loss and reduced tumor burden. Our results demonstrated that not only was aberrant DNA methylation a main contributor to bone formation impairment found in MM patients, but also its targeting by CM-272 was able to reverse MM-associated bone loss.KEY POINTS- Bone marrow-derived mesenchymal stromal cells (MSCs) from monoclonal gammopathy of undetermined significance, smoldering myeloma and myeloma patients exhibit an aberrant DNA methylome compared to their healthy counterparts.- These DNA methylation changes are associated with an altered expression of genes of the Homeobox loci that orchestrate osteogenic differentiation of mesenchymal precursors.- MM plasma cell-exposed healthy MSCs recapitulate the DNA methylation alterations observed in MSCs isolated from myeloma patients.- Dual targeting of DNMTs and the histone methyltransferase G9a with CM-272 not only controls MM tumor burden but also prevents myeloma-associated bone loss.
Increase in egg resistance to desiccation in springtails correlates with blastodermal cuticle formation: eco-evolutionary implications for insect terrestrialization
Authors: Vargas Helena Carolina Martins , Panfilio Kristen A. , Roelofs Dick , Rezende Gustavo Lazzaro 
Published: September 2019

AbstractLand colonization was a major event in the history of life. Among animals, insects exerted a staggering terrestrialization success, due to traits usually associated with post-embryonic life stages, while the egg stage has been largely overlooked in comparative studies. In many insects, after blastoderm differentiation, the extraembryonic serosal tissue wraps the embryo and synthesizes the serosal cuticle, an extracellular matrix that lies beneath the eggshell and protects the egg against water loss. In contrast, in non-insect hexapods such as springtails (Collembola) the early blastodermal cells synthesize a blastodermal cuticle. Here, we investigate the relationship between blastodermal cuticle formation and egg resistance to desiccation in the springtailsOrchesella cinctaandFolsomia candida, two species with different oviposition environments and developmental rates. The blastodermal cuticle becomes externally visible inO. cinctaandF. candidaat 22 and 29% of embryogenesis, respectively. To contextualize, we describe the stages of springtail embryogenesis, exemplified byF. candida. Our physiological assays then showed that blastodermal cuticle formation coincides with an increase in egg viability in a dry environment, significantly contributing to hatching success. However, protection differs between species: whileO. cinctaeggs survive at least 2 hours outside a humid environment, the survival period recorded forF. candidaeggs is only 15 minutes, which correlates with this species’ requirement for humid microhabitats. We suggest that the formation of this cuticle protects the eggs, constituting an ancestral trait among hexapods that predated and facilitated the process of terrestrialization that occurred during insect evolution.Research HighlightsThe formation of the blastodermal cuticle produced during early embryogenesis coincides with a higher protection against water loss in springtail (Collembola) eggs.Orchesella cinctaeggs are more resistant to drought thanFolsomia candidaones.The formation of a protective egg cuticle would be an ancestral trait among hexapods that facilitated their process of terrestrialization.Graphical AbstractGraphical Abstract legend:Eggs when laid uptake water but are also prone to water loss. Late eggs acquire some protection against water loss, but at different levels, depending on the species.
A VPS13D spastic ataxia mutation disrupts the conserved adaptor binding site in yeast Vps13
Authors: Dziurdzik Samantha K. , Bean Björn D. M. , Davey Michael , Conibear Elizabeth 
Published: September 2019

AbstractMutations in each of the four human VPS13 (VPS13A-D) proteins are associated with distinct neurological disorders: chorea-acanthocytosis, Cohen syndrome, early-onset Parkinson’s disease and spastic ataxia. Recent evidence suggests that the different VPS13 paralogs transport lipids between organelles at different membrane contact sites. How each VPS13 isoform is targeted to organelles is not known. We have shown that the localization of yeast Vps13 protein to membranes requires a conserved six-repeat region, the Vps13 Adaptor Binding (VAB) domain, which binds to organelle-specific adaptors. Here, we use a systematic mutagenesis strategy to determine the role of each repeat in recognizing each known adaptor. Our results show that mutation of invariant asparagines in repeats 1 and 6 strongly impact the binding all adaptors and block Vps13 membrane recruitment. However, we find that repeats 5 to 6 are sufficient for localization and interaction with adaptors. This supports a model where a single adaptor binding site is found in the last two repeats of the VAB domain, while VAB domain repeat 1 may help maintain domain conformation. Importantly, a disease-causing mutation in VPS13D, which maps to the highly conserved asparagine residue in repeat 6, blocks adaptor binding and Vps13 membrane recruitment when modeled in yeast. Our findings are consistent with a conserved adaptor binding role for the VAB domain and suggests the presence of as-yet-unidentified adaptors in both yeast and humans.
Honor the old, welcome the new: an account of unlearning and forgetting in NPD teams
Authors: Klammer Adrian , Gueldenberg Stefan 
Published: September 2019

Purpose
The purpose of this paper is to empirically investigate the antecedents, levers of control and outcomes of organizational unlearning and forgetting in new product development (NPD) teams.

Design/methodology/approach
This paper employs a holistic multiple-case study design. This paper gathered data from 30 individual semi-structured interviews in 10 different NPD teams as well as additional data to triangulate the findings.

Findings
The authors propose a model of unlearning and forgetting elements occurring in NPD teams. The two most prominent factors that hamper innovation are the inability to unlearn and involuntary forgetting. Failure to manage these antecedents results in the loss of crucial resources, missing innovations or intra-team tensions. Managing knowledge loss by promoting unlearning and reducing forgetting leads to enhanced creativity and flexibility, a higher chance of exceeding innovation goals, increased conversion efficiency and augmentation of existing knowledge.

Research limitations/implications
This paper contributes empirical evidence to the field of unlearning and forgetting. The model illustrates the NPD process from the perspective of organizational unlearning and forgetting. The authors examined the NPD process from an unlearning and forgetting perspective and proposed new categories of antecedents, consequences and managing unlearning and forgetting. This generates a more profound theoretical understanding of underlying knowledge loss processes in NPD teams.

Practical implications
Companies should promote unlearning and specify spatial and temporal freedom. In doing so, team members can identify outdated and obsolete knowledge. Being attentive to unlearning and forgetting processes allows teams to achieve increased creativity and flexibility.

Originality/value
This paper provides empirical evidence to generate a more profound understanding of the underlying mechanisms of knowledge loss in NPD teams. First, the authors propose a holistic model of antecedents, levers of control and consequences of both unlearning and forgetting. Second, the authors suggest that organizations can use these levers of control to successfully manage unlearning and forgetting in NPD teams.
Discrimination against gays and lesbians in hiring decisions: a meta-analysis
Authors: Flage Alexandre 
Published: September 2019

PurposeThe purpose of this paper is to evaluate the true level of discrimination against openly gay and lesbian applicants in hiring decisions in OECD countries as well as on its determinants.Design/methodology/approachThe author presents an overview of all studies conducted in order to test for discrimination against homosexual applicants in the labor market by the correspondence testing method. Moreover, the author performs a meta-analysis of correspondence tests from 18 separate studies conducted in OECD countries to test sexual orientation discrimination, containing more than 70 estimates of effects and representing a total of more than 50,000 resumes sent to employers. In addition to presenting overall results, the author focus on subgroups of specific correspondence tests in order to highlight the differences across gender, type of jobs, procedure, continent and type of information provided in applications.FindingsThe author provides evidence that sexual orientation discrimination occurs in the labor market in OECD countries, such that openly homosexual applicants face similar discrimination as ethnic minority applicants. Discrimination is significantly greater in the selection process for low-skilled than for high-skilled jobs. In the selection process for low-skilled jobs, lesbian candidates face significantly lower discrimination than gays (except in jobs that are considered “women’s” jobs). Discrimination is significantly higher in Europe than in North America. Moreover, the way sexual orientation is signaled may influence the level of discrimination found. Finally, discrimination against homosexual applicants is not only a matter of preferences: providing more positive information in applications significantly reduces the level of discrimination.Originality/valueThis paper offers the first quantitative analysis of sexual orientation discrimination in OECD countries through meta-analyses.
Rules versus relationships and campus sexual misconduct
Authors: Pappas Brian 
Published: September 2019

PurposeHow do university compliance administrators implement the rules prohibiting campus sexual misconduct? Title IX Coordinators’ authority is legal–rational and derives from the power to enforce Title IX and university rules. The paper aims to discuss this issue.Design/methodology/approachAnalyzing narratives collected from administrators at 22 large institutions of higher education, this paper distinguishes rules from relationship-oriented Coordinators and develops an understanding of how and why Title IX Coordinators utilize relational authority as they implement Title IX.FindingsThe key finding is that relational administrators exhibit less institutional authority than their rules-based counterparts and focus on their relationships with complainants and respondents over university leaders and administrators.Originality/valueWhile other researchers have focused on rules, this research demonstrates how Title IX Coordinators draw heavily on relational strategies.
Earnings management in local governments: the role of political factors
Authors: Cohen Sandra , Bisogno Marco , Malkogianni Ioanna 
Published: September 2019

PurposeThe purpose of this paper is to examine earnings management practices in local governments (LGs). The implementation of accrual accounting in LGs opens the way for empirical research on the topic, as reporting high surpluses or high deficits can be negatively interpreted by the central government, monitoring authorities, citizens and political opponents. According to public choice theory, the conflicting interests between politicians, who pursue re-election, and voters, who observe politicians’ actions to assess their alignment with social welfare, create fertile ground for earnings management practices.Design/methodology/approachThe study calculates discretionary accruals, by using the Jones (1991) model, and relates them to several political variables. It employs a large sample of Greek and Italian LGs. The Greek database covers the period from 2002 to 2015 with about 4,300 observations, and the Italian database includes the period from 2008 to 2015 with about 1,130 observations.FindingsThe findings from the analysis give evidence that LGs engage in earnings management. The principal factor is the electoral cycle, as earnings management seems to be greater when the mayor is re-elected than when the mayor is elected for the first time. Furthermore, the period before elections create conditions that cultivate earnings management attitudes.Research limitations/implicationsPrevious studies have principally investigated earnings management in the private sector. Considering that many public-sector entities have implemented accrual accounting systems, this study intends to examine earnings management behaviour at the LG level, providing interesting findings for researchers and policy makers.Practical implicationsA better understanding of the political factors and the financial conditions, which act as obstacles or facilitators, should work hand in hand with the accounting reforms. The usefulness of financial statements for decision making and control presupposes that they are of high quality, an attribute that can be impaired by earnings management.Originality/valueThis study investigates the influence of political factors on earnings management behaviour in public-sector contexts where self-interest and accountability pressures coexist.
Arousing a positive climate for knowledge sharing through moral lens: the mediating roles of knowledge-centered and collaborative culture
Authors: Lei Hui , Do Nguyen Khoi , Le Phong Ba 
Published: September 2019

Purpose
The purpose of this paper is to investigate the correlation between ethical leadership (EL), collaborative culture (CC), knowledge-centered culture and employees’ behaviors toward knowledge sharing (KS) in Chinese firms.

Design/methodology/approach
The paper used structural equation modeling to examine the level of how EL, CC and knowledge-centered culture impact on tacit and explicit KS of employees via the data collected from 319 participants in 51 Chinese firms.

Findings
The research findings show collaborative and knowledge-centered culture mediates the relationship between EL and employees’ KS behaviors. It highlights the necessity of practicing EL style to develop a positive climate aimed at positively improving tacit and explicit KS of employees.

Research limitations/implications
Future studies should focus on investigating the relationship between EL, CC and knowledge management process or the other variables to explore and maximize their potential and benefits toward key organizational outcomes.

Practical implications
This paper offers leaders a deeper understanding of the effective pathways to build positive climates for fostering employees’ tacit and explicit KS.

Originality/value
This paper is unique in the attempts to increase the understanding of moral lens by which EL might successfully arouse a positive organizational culture and foster KS behaviors in their firms.
Knowledge transfer and boundary conditions
Authors: Du Juana , Wang Rong 
Published: September 2019

Purpose
The purpose of this paper is to examine innovative practices and emphasize the mechanism of knowledge transfer across knowledge boundaries. By comparing and discussing the emerging boundary issues in knowledge transfer among small- and medium-sized enterprises (SMEs) registered in the incubation centers in China, this paper identified the main knowledge transfer approach and several contextual and organizational factors impacting knowledge transfer.

Design/methodology/approach
The authors conduct 39 semi-structured in-depth interviews with employees working within business incubation centers in China. The study uses thematic analysis for data analysis.

Findings
Our results contribute to the literature of knowledge transfer and in particular to our understanding of boundary conditions and knowledge transfer approaches in emerging economies. The results also highlight several contextual and organizational factors which impact knowledge transformation across the pragmatic boundary in the context of China.

Practical implications
First, organizations need to establish an effective process with tools to accommodate novelty; second, organizations should be aware of the impact of entrepreneurial orientation on innovative performance; and third, it will help organizations if they adopt and integrate information-rich media in managing innovative practices.

Originality/value
This research highlights the impact of contextual and organizational factors of SMEs on knowledge transfer in emerging markets and chooses incubation centers as study subjects, which is an organizational context that has not been thoroughly studied due to its unique nature and emerging complexity.
Proposing researcher brand equity index in hospitality and tourism
Authors: Köseoglu Mehmet Ali , Okumus Fevzi , Rahimi Roya 
Published: September 2019

Purpose
This study aims to propose a holistic model to rank and evaluate researchers’ performance. This holistic model is developed by focusing on brand equity, which includes three components of perceived quality, brand image and brand loyalty.

Design/methodology/approach
To show how the model works, two pseudo cases are presented.

Findings
This model encourages researchers to conduct more interdisciplinary research and collaborate with researchers from diverse backgrounds. Because the model includes publication attributes identified by researchers in the publication processes, it allows researchers to strengthen their brand equity score or performance.

Practical implications
The model is applicable not only to the fields of hospitality and tourism but also to other disciplines.

Originality/value
As one of the first studies in the field, this research introduces a holistic model to rank and evaluate researchers’ performance.
Culture and tourism: natural partners or reluctant bedfellows? A perspective paper
Authors: Richards Greg 
Published: September 2019

Purpose
This paper aims to review the development of the relationship between culture and tourism over the past 75 years and outline some future developments over the coming 75 years.

Design/methodology/approach
This paper is based on a review of previous major work on cultural tourism.

Findings
Tourism and culture have been drawn inexorably closer over the years as culture has become one of the major content providers for tourism experiences, and tourism has become one of the most important income streams for cultural institutions. In the future, this is likely to change, as cultural institutions find it increasingly difficult to maintain their authority as the dominant producers of local, regional and national culture and as tourism becomes increasingly integrated into the everyday culture of the destination.

Practical implications
Cultural institutions will need to change their relationship with tourism as flows of tourists become more prevalent and fragmented.

Social implications
The authority of high cultural institutions will be eroded as tourists increasingly seek authenticity in the culture of everyday life and the ‘local’.

Originality/value
This study reviews the dynamics of the cultural field and sketches the long-term future development of the relationship between tourism and culture.
Business travel: a perspective paper
Authors: Lubbe Berendien 
Published: September 2019

Purpose
The purpose of this paper is to provide a brief perspective on the growth of business travel over the past 60 years and how it may unfold in the future, highlighting certain themes and noting limitations in the research.

Design/methodology/approach
This paper is based on selected academic literature and industry sources on business travel which briefly reviews its growth and directions of research in this field.

Practical implications
The paper distinguishes between different types of business travel and provides a bird's eye view of the future.

Originality/value
The review distinguishes between different forms of business travel and concludes that greater clarity of the business travel concept will enable research to be conducted within a properly defined theoretical framework.
Flow-based destination management and marketing: a perspective article
Authors: Reinhold Stephan , Laesser Christian , Beritelli Pietro 
Published: September 2019

Purpose
This paper aims to provide a selective review of sectoral and academic developments that have led to the flow-based view of destination management and marketing and inspires future work.

Design/methodology/approach
A review of the relevant literature serves as a foundation for the discussion of the flow-based view of destination management and marketing. From the results of this review, future prospects for practice and research are derived.

Findings
Destination management and marketing has undergone many changes in the past and is subject for some major overhauls in the future.

Originality/value
The paper inspires in terms of rather asking questions for the future than finding answers from the past.
Image of Poland as perceived by German and British medical tourists
Authors: Dryglas Diana , Lubowiecki-Vikuk Adrian 
Published: September 2019

PurposeThe purpose of this paper is to identify Poland’s image as a medical tourism destination (MTD).Design/methodology/approachSurvey data were collected from 282 German and British medical tourists, using a self-administered questionnaire. The Computer-Assisted Web Interviewing method was used to conduct the survey. Subsequently, the responses were analysed using advanced statistical tools (McNemar’s exact test, Cochran’s Q test and Chi-square test).FindingsBefore visiting Poland, the respondents perceived the country through the prism of medical attributes, whereas after the visit, they perceived it through the prism of non-medical attributes.Research limitations/implicationsIdentification of a set of MTD image characteristics has important implications for scholars, allowing them to understand attributes which shape projected and perceived MTD image. Such construct can also be a useful tool for marketing planners, destination managers and marketers to create an effective marketing policy and projected image of MTDs based on these features.Originality/valueThe study fills an important gap regarding the lack of conceptual and empirical content allowing for exploration of MTD image.