bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type 1 diabetes mellitus-associated genetic variants contribute to overlapping immune regulatory networks
Authors: Nyaga Denis M. , Vickers Mark H. , Jefferies Craig , Perry Jo K. , O’Sullivan Justin M. 
Published: May 2018

AbstractType 1 diabetes (T1D) is a chronic metabolic disorder characterised by the autoimmune destruction of insulin-producing pancreatic islet beta cells in genetically predisposed individuals. Genome-wide association studies (GWAS) have identified over 60 risk loci across the human genome, marked by single nucleotide polymorphisms (SNPs), which confer genetic predisposition to T1D. There is increasing evidence that disease-associated SNPs can alter gene expression through spatial interactions that involve distal loci, in a tissue-and development-specific manner. Here, we used three-dimensional (3D) genome organization data to identify genes that physically co-localized with DNA regions that contained T1D-associated SNPs in the nucleus. Analysis of these SNP-gene pairs using the Genotype-Tissue Expression database identified a subset of SNPs that significantly affected gene expression. We identified 298 spatially regulated genes including HLA-DRB1, LAT, MICA, BTN3A2, CTLA4, CD226, NOTCH1, TRIM26, CLEC2B, TYK2, and FLRT3, which exhibit tissue-specific effects in multiple tissues. We observed that the T1D-associated variants interconnect through networks that form part of the immune regulatory pathways, including immune-cell activation, cytokine signalling, and programmed cell death protein-1 (PD-1). These pathways have been implicated in the pancreatic beta-cell inflammation and destruction as observed in T1D. Our results demonstrate that T1D-associated variants contribute to adaptive immune signalling, and immune-cell proliferation and activation through tissue and cell-type specific regulatory networks.Author SummaryAlthough genome-wide association studies have identified risk regions across the human genome that predispose individuals to the development of type 1 diabetes (T1D), the mechanisms through which these regions contribute to disease is unclear. Here, we used population-based genetic data from genome-wide association studies (GWAS) to understand how the three-dimensional (3D) organization of the DNA contributes to the differential expression of genes involved in immune system dysregulation as observed in T1D. We identified interconnected regulatory networks that affect immune pathways (adaptive immune signalling and immune-cell proliferation and activation) in a tissue and cell-type specific manner. Some of these pathways are implicated in the pancreatic beta-cell destruction. However, we observed other regulatory changes in tissues that are not typically considered to be central to the pathology of T1D, which represents a novel insight into the disease. Collectively, our data represent a novel resource for the hypothesis-driven development of diagnostic, prognostic and therapeutic interventions in T1D.
Microbiome disturbance and resilience dynamics of the upper respiratory tract in response to influenza A virus infection in humans and ferrets
Authors: Kaul Drishti , Rathnasinghe Raveen , Ferres Marcela , Tan Gene S. , Barrera Aldo , Pickett Brett E. , Methe Barbara A. , Das Suman , Budnik Isolda , Halpin Rebecca A. , Wentworth David , Schmolke Mirco , Mena Ignacio , Albrecht Randy A. , Singh Indresh , Nelson Karen E. , García-Sastre Adolfo , Dupont Chris L. , Medina Rafael A. 
Published: May 2018

AbstractInfection with influenza can be aggravated by bacterial co-infections, which often results in disease exacerbation because of host responses and cellular damage. The native upper respiratory tract (URT) microbiome likely plays a role, yet the effects of influenza infection on the URT microbiome are largely unknown. We performed a longitudinal study to assess the temporal dynamics of the URT microbiomes of uninfected and influenza virus-infected humans and ferrets. Uninfected human patients and ferret URT microbiomes had stable “heathy ecostate” communities both within and between individuals. In contrast, infected patients and ferrets exhibited large changes in bacterial community composition over time and between individuals. The “unhealthy” ecostates of infected individuals progressed towards the “healthy ecostate” over time, coinciding with viral clearance and recovery. Blooms of Pseudomonas were a statistically associated constant in the disturbed microbiomes of infected individuals. The dynamic and resilient nature of the microbiome during influenza virus infection in multiple hosts provides a compelling rationale for the maintenance of the microbiome homeostasis as a potential therapeutic target to prevent IAV associated bacterial co-infections.One Sentence SummaryDynamics of the upper respiratory tract microbiome during influenza A virus infection
Anti-inflammatory properties of natural ingredients used in combinations on adjuvant induced arthritis in rats
Authors: St-Pierre Amélie , Desrosiers Véronique , Dufresne France , U. Blier Pierre 
Published: May 2018

AbstractBackground: Rheumatoid arthritis has seen a significant increase in both incidence and prevalence and its treatments show limited efficiency due to their undesirable effects on patient health. Therefore, major interests lie in the development of treatments with drugs derived from plants or other natural sources with little adverse effects as an alternative to current treatments.Hypothesis/Purpose: The present study evaluates the therapeutic effects of glucosamine against rheumatoid arthritis in combination with hyaluronic acid, resin extract ofBoswellia serrataor a bark extract ofSalix albaon an animal model. We suggest that combinations with plants could improve the attenuation of arthritis symptoms and articular inflammation.Study design: We used Freund’s complete adjuvant on rats as models of rheumatoid arthritis. Individuals were separated into eight experimental groups: a control group without arthritis, one with arthritis and without treatment, and six other groups receiving a daily therapeutic treatment from days 14 to 29.Methods: Hind-paw thickness and arthritis scores were measured at days 0, 3, 6 and 9 post-induction, and then every day from days 12 to 29 with a digital caliper and a score system respectively. At the end of the treatment, the mRNA content of three pro-inflammatory cytokines from cartilage was measured using real-time PCR. The total antioxidant activity was evaluated with an Antioxidant Assay Kit.Results: Treatments withBoswellia serrataandSalix alba(Glu+Hyal A+Bosw, Glu+Bosw+Sal, Glu+BoswandGlu+Hyal A+Sal) saw significant reductions in hind-paw thickness and arthritis scores at the end of the experiment when compared to the untreated group. Expression of pro-inflammatory geneIL 17Awas also reduced, but only theGlu+Hyal A+Salcombination significantly decreased the expression ofIL-1βandTNF-α. The total antioxidant activity in blood plasma significantly increased in groups treated with plant extracts.Conclusion: The addition ofBoswellia serrataand/orSalix albaattenuates clinical signs of rheumatoid arthritis in Freund’s complete adjuvant-induced arthritis in rats likely due to both their anti-inflammatory and antioxidant properties.
Common genomic regions underlie natural variation in diverse toxin responses
Authors: Evans Kathryn S. , Brady Shannon C. , Bloom Joshua S. , Tanny Robyn E. , Cook Daniel E. , Giuliani Sarah E. , Hippleheuser Stephen W. , Zamanian Mostafa , Andersen Erik C. 
Published: May 2018

AbstractPhenotypic complexity is caused by the contributions of environmental factors and multiple genetic loci, interacting or acting independently. Studies of yeast andArabidopsisfound that the majority of natural variation across phenotypes is attributable to independent additive quantitative trait loci (QTL). Detected loci in these organisms explain most of the estimated heritable variation. By contrast, many heritable components underlying phenotypic variation in metazoan models remain undetected. Before the relative impacts of additive and interactive variance components on metazoan phenotypic variation can be dissected, high replication and precise phenotypic measurements are required to obtain sufficient statistical power to detect loci contributing to this missing heritability. Here, we used a panel of 296 recombinant inbred advanced intercross lines ofCaenorhabditis elegansand a high-throughput fitness assay to detect loci underlying responses to 16 different toxins, including heavy metals, chemotherapeutic drugs, pesticides, and neuropharmaceuticals. Using linkage mapping, we identified 82 QTL that underlie variation in responses to these toxins and predicted the relative contributions of additive loci and genetic interactions across various growth parameters. Additionally, we identified three genomic regions that impact responses to multiple classes of toxins. These QTL hotspots could represent common factors impacting toxin responses. We went further to generate near-isogenic lines and chromosome-substitution strains and then experimentally validated these QTL hotspots, implicating additive and interactive loci that underlie toxin-response variation.
Women on boards of directors in Latin America: building a model
Authors: Heller Lidia , Gabaldon Patricia 
Published: May 2018

PurposeThrough an analysis of 15 Latin American countries, the purpose of this paper is to explore the importance of several institutional variables (economic, regulatory, and cultural), which affect women’s careers towards being members of boards of directors in the region.Design/methodology/approachBased on primary and secondary information, the authors carry out multivariate analyses to understand the institutional reasons affecting the reduced presence of women on boards of directors in the region.FindingsTheir findings reveal differences within the region, the importance of protecting women’s professional careers in the labour market, and the effect of cultural dimensions, such as masculinity and power distance.Research limitations and implicationsThe analysis provides an updated cross-section of the institutional and cultural conditions of the 15 countries, considering the limitations to developing data in the region.Practical implicationsLatin America has witnessed important changes in the dynamics of the labour market over recent decades: women’s participation in the labour force is on the increase, and corporate strategy is evolving towards the incorporation of practices and initiatives to manage the diversity of their talents. However, the presence of women in leadership positions is a pending subject. This study, in part, reveals the institutional origin of gender inequality on boards of directors in the region. The analysis provides essential tools for public policy and for companies to help promote female leadership in the region.Originality/valueRecent debate and research on the scarce participation of women on corporative boards of directors have revealed a growing interest in analysing the causes of such issues despite the progress recorded in terms of gender equity in most societies. Studies on the topic in Latin America are scarce and the aim of this paper is to help to fill part of this gap.
The “invisible” hand: views from UK institutional investors
Authors: Allcock Deborah 
Published: May 2018

PurposeInvestors are called to be good stewards/trustees of their investments, often on behalf of third parties. In light of this fiduciary responsibility, and the conundrum of public criticism potentially impacting on share price, this paper aims to use the basis of the UK governance code to explore what important dialogue investors really have with their holdings to support good governance.Design/methodology/approachSemi-structured telephone interviews with eight institutional investors explore governance issues and investor company dialogue, giving insights into the aspects of the importance of their part in the UK corporate governance code.FindingsRather than being sleeping lions, investors positively engage with companies, with regular communication being high on their agenda and not always via the annual general meeting. There is a preference to engage directly with the company rather than in public view or via share dumptin. Thus, we often do not see their actions around their fiduciary duties as often they avoid public criticism or any visibility that could do reputational harm and decrease company value.Research limitations/implicationsThis dialogue was just before the point of the exposure of the financial crisis; however, it shows the importance that investors give to taking their responsibilities seriously. Importantly, it provides a springboard for further debate following the financial crises and the updates of the financial environment.Practical implicationsEven though policy seeks engagement, the nuances of the investor dialogue are under explored compared to visible quantitative metrics. This dialogue assures that investors are active, even if their engagement is not public and can be deemed as hidden.Originality/valueComplementing quantitative studies, this paper explores a qualitative approach, uniquely sharing insights into a hidden and little explored world of fiduciary dialogue.
A process model of social intelligence and problem-solving style for conflict management
Authors: Rahim Afzalur , Civelek Ismail , Liang Feng Helen 
Published: May 2018

PurposeThis study aims to explore the relationship between social intelligence (SI) and problem-solving (PS) style of handling conflict.Design/methodology/approachData on SI and PS were collected with questionnaires from 406 faculty members, and the data were averaged by departments. This resulted in a sample of 43 departments, and all the data analyses were performed with this sample of 43. SI is defined as the ability to be aware of relevant social situations, to handle situational challenges effectively, to understand others’ concerns and feelings and to build and maintain positive relationships in social settings.FindingsData analyses with LISREL at the department level suggest that SI is positively associated with PS.Research limitations/implicationsData were collected from only one public university in the USA, which might limit the generalizability of the results. The department chairs need to acquire the four components of SI to improve faculty members’ PS. This will hopefully lead to constructive management of many faculty–department chair conflicts.Originality/valueOne of the strengths of this study is that the measures of endogenous and exogenous variables were analyzed at the department level, not individual level. This study contributed to our understanding of the relationships of situational awareness, situational response, cognitive empathy and social skills with each other and to PS.
The role of European R&D projects for SMEs’ resource development: an IMP perspective
Authors: Ciarmatori Fabrizio , Bocconcelli Roberta , Pagano Alessandro 
Published: May 2018

Purpose
The purpose of this paper is to provide a contribution on the role of European R&D projects (ERDPs) on small and medium enterprises’ (SMEs) resource development.

Design/methodology/approach
This paper adopts a qualitative methodology based on a longitudinal case study. The case analysis concerns Gamma, a small high-tech firm based in Italy, active in nanotechnologies since 2005 as a research spin-off and since its establishment active in ERDPs. The analysis is developed along three main phases of development where the company participated to different ERDPs.

Findings
The empirical analysis highlights that since its establishment, Gamma has been able to increasingly exploit participation in ERDPs, in order to gain access to financial and technological resources. Such active and continuous participation fostered the development of both advanced technological and organizational resources, which then allowed the company to survive and play a growing role as a well-known technology partner in the nanotechnology field in Italy and Europe.

Originality/value
Adopting an IMP perspective, the paper provides a contribution on the managerial dimension of SMEs’ participation in ERDPs – which represents a neglected topic in the existing literature – on two distinct grounds: resource development process and networking processes. With respect to resource development processes in ERDPs, this case study underscores the relevance of ERDPs for developing both technological and organizational resources, highlighting the relevance of project management-related knowledge. In terms of networking processes, this paper highlights the need to fully understand the interplay of ERDP networks and business networks.
Network approach to public-private organizing of destinations
Authors: Elbe Jörgen , Gebert Persson Sabine , Sjöstrand Fredrik , Ågren Karin 
Published: May 2018

Purpose
This paper explores a type of organizing that can be found in tourist destinations that are administratively bound to a specific geographic area in the intersection of public and private context. The purpose of this paper is to contribute to the understanding of the organizing of activities within destinations and also to contribute theoretically and conceptually to how place dependency and public/private can be understood from an industrial marketing and purchasing (IMP) network perspective.

Design/methodology/approach
The research approach has its origin in an ongoing multi-disciplinary and longitudinal case study.

Findings
By applying a network approach to the organizing of destinations, where interaction of relationships, resources, actors and activities play an essential role, a number of propositions have been put forth so as to provide for a better understanding of place-specific organizing, in the intersection between public and private interests.

Research limitations/implications
The paper is conceptual and more empirical studies are needed to test the findings. One implication to consider in future empirical studies is the tensions between created and organic networks that exist in public and private place partnerships.

Practical implications
The paper provides insights into factors affecting destination management.

Social implications
With an emphasis on a socio-political context, the opportunities and limitations that exist between public and private sectors are discussed.

Originality/value
The paper sheds light on a neglected aspect of a contemporary phenomenon where the IMP network approach could contribute to the understanding of destination marketing or management organization that are bound to a specific place in the intersection between the public and private context. The area of public-private organizing is a topic that may also add new aspects to the IMP community.
La cuarta hélice y la financiación de la innovación
Authors: Sierra Jaime 
Published: May 2018

Propósito
Este artículo aborda la relación emergente entre la sociedad civil y el sistema de innovación en América Latina y el Caribe –la financiación de la innovación, en particular– con la intención de sugerir una perspectiva conceptual diferenciada y plantear algunos de los interrogantes más relevantes en la actualidad.

Enfoque
Existe una desconexión estructural entre la sociedad civil y el mundo de la innovación. Empero, la exploración de las divergencias entre las perspectivas neo-institucional y neo-evolucionista de la triple hélice permite plantear que la evolución de los financiadores en distintos contextos puede generar una articulación emergente. Los efectos sobre la “sistematicidad” existente, en particular en América Latina y el Caribe, dependerán en buena medida del enfoque conceptual adoptado y de su institucionalización en términos de reestructuración de la sistematicidad de los sistemas de innovación y su governance.

Hallazgos
La evolución de las relaciones entre los mecanismos de financiación emergentes y los proyectos innovadores en América Latina y el Caribe constituye tanto una oportunidad como un peligro. Si se logra re-estructurar la “sistematicidad”, la región podría seguir una senda con altas expectativas; si persisten las sub-dinámicas tradicionales, el fenómeno emergente podría verse despojado de todo su potencial.

Contribución
Se propone un análisis conceptual y práctico diferente del tema de la financiación de la innovación, con énfasis en el caso latinoamericano y caribeño. Adicionalmente, se sugieren vías de investigación que permiten reducir la incertidumbre sobre la relación entre los actores del sistema de innovación y la sociedad civil y su impacto potencial.

Palabras clave
Crowd-funding, América Latina y el Caribe, Cuarta hélice, Financiación de la innovación, Sistemas de innovación

Tipo de artículo
Trabajo de investigación
Collaborative consumption: a business model analysis of second-hand fashion
Authors: Gopalakrishnan Sivasankari , Matthews Delisia 
Published: May 2018

Purpose
The purpose of this paper is to analyze the business model of second-hand fashion stores and explore their challenges/opportunities and suggest potential strategies for second-hand fashion retail stores.

Design/methodology/approach
A qualitative research method using in-depth interviews of convenience sample of owners/store managers from within the USA was employed.

Findings
Contrasting the traditional retail stores, customers are the primary partners and suppliers of second-hand fashion stores. These stores retain minimal profits given a business model that typically involves sharing profits with customers. Cheaper price, thrill of finding great deals, value for brands and variety are the primary reasons mentioned by respondents for shopping at second-hand stores.

Research limitations/implications
Limitations include the use of a convenience sample of store owners/managers as well as the research is limited to women and children’s stores. Respondents of the study were from the same geographical region and the characteristics of the redistribution markets may vary in a different region.

Practical implications
As a means to foster textile waste reduction through second-hand clothing business, these stores could adopt innovative revenue streams, additional partnerships, and improved fashion and store appeal that may be effective in increasing profits and the number of customers.

Originality/value
This study is one of the early attempts to examine the business model of second-hand fashion stores, a form of collaborative consumption in the fashion context. The study contributes in promoting second-hand fashion stores as a sustainable business model in the fashion industry.
International mobility and well-being of public sector expatriates
Authors: Waibel Stine , Aevermann Tim , Rueger Heiko 
Published: May 2018

Purpose
The purpose of this paper is to examine the health-related well-being of public sector expatriates paying particular attention to the family situation.

Design/methodology/approach
A cross-sectional survey was conducted among the entire staff of the German Foreign Service (GFS), resulting in a response rate of 35.5 percent (analytical sample n=1,390). Partnership status, childlessness, and experiences of partnership break-ups were analyzed by gender and by age. Using OLS regression, the authors examine how gender and individual perceptions of conflict between international relocation and family stability and formation contribute to subjective well-being.

Findings
The results show that females are significantly over-represented among GFS employees who experience partnership instability as well as among single and childless employees. Yet barriers to partnership and family formation appear to be increasing for younger cohorts of male employees.

Practical implications
Unstable families can jeopardize the well-being of employees highlighting that expatriates’ relationship and family needs are insufficiently met in high mobility contexts.

Originality/value
The focus on family formation challenges in non-corporate expatriation makes a novel contribution to the literature and practice of expatriate management, as the system-wide rotational staff mobility of public service institutions has received minor attention.