bluuebunny/crossref_metadata_2025 huggingface dataset:
BINDING PROTEIN Is a Master Regulator of the Endoplasmic Reticulum Stress Sensor/Transducer bZIP28 in Arabidopsis
Authors: Srivastava Renu , Deng Yan , Shah Shweta , Rao Aragula Gururaj , Howell Stephen H.
Published: April 2013

BINDING PROTEIN (BiP) is a major chaperone in the endoplasmic reticulum (ER) lumen, and this study shows that BiP binds to the C-terminal tail of the stress sensor/transducer bZIP28, a membrane-associated transcription factor, retaining it in the ER under unstressed conditions. In response to ER stress, BiP dissociates from bZIP28, allowing it to be mobilized from the ER to the Golgi where it is proteolytically processed and released to enter the nucleus. Under unstressed conditions, BiP binds to bZIP28 as it binds to other client proteins, through its substrate binding domain. BiP dissociates from bZIP28 even when bZIP28's exit from the ER or its release from the Golgi is blocked. Both BiP1 and BiP3 bind bZIP28, and overexpression of either BiP detains bZIP28 in the ER under stress conditions. A C-terminally truncated mutant of bZIP28 eliminating most of the lumenal domain does not bind BiP and is not retained in the ER under unstressed conditions. BiP binding sites in the C-terminal tail of bZIP28 were identified in a phage display system. BiP was found to bind to intrinsically disordered regions on bZIP28's lumen-facing tail. Thus, the dissociation of BiP from the C-terminal tail of bZIP28 is a major switch that activates one arm of the unfolded protein response signaling pathway in plants.
Four major disaster occurrences and the Spanish language media: a lack of risk communication
Authors: David Benavides Abraham
Published: April 2013

Purpose

– The Hispanic community is the fastest growing ethnic group in the USA and is currently the largest minority group with tremendous buying power. This trend has seen a significant growth with respect to the Spanish-language media in recent years. Along with the media ' s ability to entertain, comes the responsibility to educate and warn its audiences of eminent threats and disasters. The aim of this paper is to look at the Spanish-language media ' s efforts to warn and prepare its listeners for local and national emergencies.

Design/methodology/approach

– Using descriptive and explanatory methods the author looks at the failures of the Spanish language media to communicate emergency warnings in both the Saragosa, Texas tornado and in the case of hurricane Katrina.

Findings

– Research indicated that pressure from constituents, however, forced a change on the Spanish language industry.

Research limitations/implications

– The research was limited by not having first hand contact with the Spanish language media.

Practical implications

– The practical implication of this research which has social overtones is that providing disaster warnings to the non-English speaking population in the USA is achievable. Emergency managers and first responders need to be aware of issues regarding non-English speakers.

Social implications

– The implications for this research is that all individuals will be notified of emergencies even non-English speakers.

Originality/value

– The issues on non-English speakers in emergency situations have come up before. Nevertheless, this work identifies a practical solution by involving the Spanish language media in emergency alerts. It is essential that this tremendous resource be involved in emergency alerts.
A comparative study on the national counterpart aid model for post-disaster recovery and reconstruction
Authors: Xu Jiuping , Lu Yi
Published: April 2013

Purpose

– External assistance is often urgently required when an area is struck by a catastrophe. Central government-oriented aid (CGA), national non-governmental organizations aid (NNA), and international humanitarian aid (IHA) are three typical aid models, and national counterpart aid (NCA) is an innovative model for post-Wenchuan earthquake recovery and reconstruction (PWERR). The purpose of this paper is to make a comparative study of the aid models in order to develop recommendations on external assistance for better post-disaster recovery and reconstruction (PDRR).

Design/methodology/approach

– This study was performed in three steps: a case study on the NCA model during the PWERR; a documentary research on the CGA, NNA and IHA models; and a comparative analysis of the four models.

Findings

– The results of the comparative study show that the NCA model is more efficient and effective than the other three typical aid models. However it must be based on the premise of a centralized government.

Practical implications

– The NCA model contributes to disaster management in a developing country context. It develops a viable model for developing countries in coping with the catastrophe, can enhance their ability for domestic self-assistance, and has reference to the construction of national integrated disaster management systems.

Originality/value

– This paper empirically researches the innovative NCA model, and compares it with commonly used aid models for the PDRR. Although it is a Chinese experience, the systematic inter-governmental collaboration of the NCA model has reference to other countries in disaster management.
The effect of communication during mass decontamination
Authors: Carter Holly , Drury John , Rubin G. James , Williams Richard , Amlôt Richard
Published: April 2013

Purpose

Reports from small‐scale incidents in which decontamination was conducted suggest that a successful communication strategy is vital in order to increase public compliance with, and reduce public anxiety about, decontamination. However, it has not been possible to examine public behaviour during large scale incidents involving decontamination. The aim of the research reported here was to examine the relationship between people's positive perceptions of responding agencies’ communication strategies and relevant outcome variables, such as level of compliance and level of reassurance, in several field exercises involving mass decontamination.

Design/methodology/approach

Data were collected using feedback questionnaires completed by simulated casualties, which contained items relating to casualties’ perceptions of the success of responding agencies’ communication strategies, their confidence in emergency responders, and their compliance with the decontamination process. Path analysis was used to examine the relationships between variables.

Findings

Results show a significant relationship between responding agencies’ communication strategies, level of public reassurance, and level of public compliance. The relationship between responders’ communication strategies and the outcome variables was partially mediated by public confidence in responders.

Practical implications

Emergency responders should focus on communication with members of the public as a key element of the decontamination process, as failure to do so could result in high levels of anxiety and low levels of compliance among those who are affected.

Originality/value

This research highlights the importance of effective responder communication strategies. Further, findings indicate the value of examining feedback from field exercises in order to facilitate a greater understanding of public experiences of the decontamination process.
Media and social amplification of risk: BSE and H1N1 cases in South Korea
Authors: Bum Chung Ji , Woong Yun Gi
Published: April 2013

Purpose

This study aims at exploring the topology of two risk communication cases, Bovine Spongiform Encephalopathy (BSE) in 2008 and H1N1 in 2009, in South Korea and investigating the progression of risk events related to media's role in risk amplification.

Design/methodology/approach

Content analysis of major Korean media is conducted. BSE and H1N1 stories in 2008 and 2009 are collected and analyzed. First, the basic nature of media coverage of the events such as frequency of stories is surveyed. Second, framings adopted in media to cover two cases are analyzed.

Findings

The result indicates that unfolding events related to BSE and H1N1 risk show a similar timeline with the frequency of media coverage of the given risks. Also, media adopted political framings for BSE and health/medial framings for H1N1.The authors cautiously suggest that the framings in media have influenced the politicization of BSE risk issue among the public, but, at the same time, the media framings on H1N1 have attenuated potential politicization of H1N1's risk.

Originality/value

This paper demonstrates the relationship between the process of social amplification of risk and media framings in Korea.
Systematic review on B2B branding: research issues and avenues for future research
Authors: Keränen Joona , Piirainen Kalle A. , Salminen Risto T.
Published: April 2013

Purpose

The purpose of this study is to review the current body of the B2B branding literature, and identify research issues that hamper current B2B branding research.

Design/methodology/approach

The study employs a systematic review, and identifies 73 relevant journal publications from the years 1973‐2010 that were subsequently evaluated for further analysis.

Findings

This study identifies five possible issues hampering current B2B branding research: the lack of systematic theory development, the transference of consumer concepts, the dominance of quantitative research, the lack of longitudinal research, and the focus on single industries.

Research limitations/implications

This study considers only published journal articles, excluding books and conference proceedings. By highlighting the research issues, this paper aims to direct research efforts to areas where they will have the most impact, and thus aid more rapid advancement of B2B branding as a discipline.

Originality/value

This study provides the first systematic review to identify and evaluate the current B2B branding literature. The review identifies the key literature related to B2B branding, provides an overview of past research and identifies emerging research issues to be addressed in future research.
Role of content strategy in social media brand communities: a case of higher education institutes in India
Authors: Chauhan Kalpana , Pillai Anandan
Published: April 2013

Purpose

The aim of this study is to attempt to understand the role of content strategy followed by leading higher education institutes in India which have created brand community on social media web sites to initiate and enhance customer engagement. The impact of content strategy variables – content type, posting agility, posting day and content context on number of likes and number of comments, which were manifest variables for customer engagement was assessed here.

Design/methodology/approach

This study follows a positivistic paradigm and employs case study research design. The data were collected by netnography method from brand communities on social networking web sites. The data were collected on a longitudinal basis for one year. Ten brand communities were tracked for the period and the analysis is based on total 1,440 posts made by brands during this period.

Findings

The content type and content agility were found to have significant impact on number of likes and comments, which were treated as manifest variables for customer engagement. The two‐way interaction indicated that content type and content context had significant impact on number of likes and comments.

Research limitations/implications

It is one of the first attempts to characterize the relationship between a firm's content strategy of its BC on social networking sites and the customer engagement. This study identifies various manifest variables for both the content strategy of the firm and the customer engagement.

Practical implications

This study would facilitate practicing community managers and content managers to understand and develop content strategy which would lead to desired customer engagement on brand communities created on social media.

Originality/value

With the application of this study's results, an organization should be able to avoid misuse of its social media marketing efforts, and should be able to focus on its content strategy, which maximises customer engagement on its brand community.
Reassessing retailers' usage of partially comparative pricing
Authors: Mustapha Mohammed Shazad , Miniard Paul W.
Published: April 2013

Purpose

The purpose of this paper is to assess the robustness of effects found by Barone et al. that partially comparative pricing enhances consumers' relative price beliefs about its comparatively priced products, but risks adversely affecting these beliefs about the retailer's non‐comparatively priced products.

Design/methodology/approach

Research uses an experimental methodology in which the presence or absence of a price comparison is manipulated and the effects on relative price beliefs about non‐comparatively priced products are assessed.

Findings

Four studies replicated Barone et al.'s findings that a competitive price comparison enhances consumers' relative price beliefs about comparatively priced products, but did not replicate their findings that these beliefs about the non‐comparatively priced products are affected adversely unless suspicion was induced experimentally. Otherwise, consumer suspicion about the lack of price comparisons, found to be a driver of the adverse effects in Barone et al., did not spontaneously emerge in the current research.

Research limitations/implications

Research examines only university students in a controlled setting devoid of real‐world distractions. Like Barone et al., effects focus on non‐comparatively priced products in categories lacking any price comparison rather than the non‐comparatively priced products residing within the same category as the comparatively priced product. Findings reinforce the value of replication.

Practical implications

The potential risks to retailers of using partially comparative pricing appear far less prevalent than observed previously.

Originality/value

The paper raises questions about the stability of consumer response, particularly those involving consumer suspicion, to pricing tactics.
Scan‐4‐Light: a Searchlight function horizon scanning and trend monitoring project
Authors: Saritas Ozcan , Miles Ian
Published: April 2013

Purpose

The current paper aims to present the Scan‐4‐Light study, which was conducted for the systematic scanning and analysis of the Searchlight newsletters as a rapidly growing collection of articles on trends and topics in development and poverty.

Design/methodology/approach

Built upon the concept of the systemic foresight methodology, the Scan‐4‐Light approach involves the integrated use of horizon scanning, network analysis and evolutionary scenarios combined with expert consultations and workshops. The study identified the emerging trends, issues, weak signals and wild cards; created high‐value visualisations to emphasize the results and findings; and produced narratives to increase the impact and awareness of the development issues.

Findings

The Scan‐4‐Light project has resulted in a large number of specific outputs, providing the views of the Searchlight newsletters' contents at various levels of granularity. It has set out to show how the tools used here can be applied to illustrate the relationships among issues, and how these vary across countries and regions over time, and are linked to various stakeholders and possible solutions to problems.

Research limitations/implications

Scan‐4‐Light demonstrates how foresight tools and techniques can be used for the analysis of complex and uncertain issues, such as development and poverty, in a systemic way.

Practical implications

The Scan‐4‐Light approach can be applied in a number of areas for scanning and identifying emerging trends and issues, and understanding the relationships between systems and solutions.

Social implications

The paper gives evidence that most of the issues, if not all, related to development are not isolated, but interlinked and interconnected. They require more holistic understanding and intervention with an effective collaboration between stakeholders.

Originality/value

A demonstration of a novel scanning approach is presented in the paper.
Foresight and “grand challenges” within research and innovation policies
Authors: Rhisiart Martin
Published: April 2013

Purpose

The paper seeks to discuss how foresight is used to understand the implications of global changes for research and innovation policies. It aims to present a recent Irish case study that identified grand challenges in the national context, with their implications for research and innovation.

Design/methodology/approach

The foresight project is described and provides knowledge and analysis for a broader, national research prioritisation exercise. The paper analyses the implementation of the Irish foresight exercise and the main outputs generated. It connects the results of the project with the literature on foresight, innovation and grand challenges.

Findings

The emergence of grand challenges within research and innovation policy discourse in Europe has refreshed key questions for foresight theory and practice. Although many grand challenges have relatively clear implications for research and innovation (investment), others do not. A bottom‐up, participatory process produced a broader set of grand challenges.

Research limitations/implications

The concept of grand challenges is still relatively new.

Practical implications

Not all research and innovation priorities are linked to grand challenges. National policies need to take account of grand challenges whilst continuing to support other research and innovation needs.

Originality/value

The paper introduces a novel approach for identifying grand challenges and responses within the research and innovation system through a bottom‐up process.
Depression in patients with pemphigus: Is it a major concern?
Authors: Layegh Pouran , Mokhber Naghmeh , Javidi Zari , Mashhadi Mahdi Parvizi , Moghiman Toktam
Published: April 2013

It is suggested that some dermatological diseases due to their chronicity, impact on the body image, unlikelihood of complete recovery and frequent recurrences are one of the major predisposing factors towards depression. Therefore, we aimed to evaluate the rate and level of depression among pemphigus vulgaris and pemphigus foliaceus patients, two of the most common causes of hospitalization in dermatology units. This research was conducted on 55 patients with active pemphigus vulgaris and pemphigus foliaceus referring to pemphigus clinics or admitted as inpatients to the dermatology ward of Qaem and Imam Reza hospitals, Mashhad, Iran, from April 2008 to September 2009. The research tool was the Beck Depression Inventory. Collected data was analyzed by χ2‐test Student's t‐test. Twenty‐six (47.3%) patients were female and 29 (52.7%) were male. The mean age was 42.34 ± 18.98 years. The prevalence rate of clinical depression was 28% in pemphigus vulgaris and 20% in pemphigus foliaceus cases. Depression prevalence showed no significant difference between these two groups (P = 0.873). In conclusion, pemphigus patients are at risk for mild depression.
Effects of TLC‐Ag dressings on skin inflammation
Authors: Bisson Jean‐François , Hidalgo‐Lucas Sophie , Bouschbacher Marielle , Thomassin Laetitia
Published: April 2013

The TLC‐Ag dressings, a combination of technology lipido‐colloid and silver salts, are used to promote healing in wounds with risks or signs of local infection, thanks to the antimicrobial properties of the silver salts. Nanocrystalline silver dressings containing nanocrystalline silver, also used to improve wound healing, present both antimicrobial and anti‐inflammatory effects. The aim of this study was to investigate the anti‐inflammatory effects of TLC‐Ag dressings in a model of chronic skin inflammation induced by repeated application of 12‐O‐tetradecanoylphorbol‐13‐acetate to the skin of hairless mice, in comparison with TLC dressing, Silcryst nanocrystalline dressing, desonide cream 0.05%, a corticoid cream used as positive control, and gauze. Daily treatments of the mice began 7 days after the start of induction of chronic skin inflammation and lasted for 7 days. A macroscopic score was performed daily during the treatment period until the mice killing on day 15 and skin samples were taken for histopathological analysis. TLC‐Ag reduced significantly the macroscopic score of chronic skin inflammation from day 10 in comparison with gauze and TLC dressing, similarly to Silcryst nanocrystalline dressing and desonide cream, which presented the best anti‐inflammatory effects. No significant differences were observed between TLC dressing and gauze. TLC‐Ag reduced significantly the microscopic score of chronic skin inflammation in comparison with TLC dressing and gauze, similarly to Silcryst nanocrystalline dressing but significantly less than desonide cream. These results demonstrate that TLC‐Ag dressings present significant anti‐inflammatory effects on chronic skin inflammation. They can improve wound healing, due to both the antimicrobial and anti‐inflammatory properties.
Successful treatment with 308‐nm monochromatic excimer light and subsequent tacrolimus 0.03% ointment in refractory plasma cell cheilitis
Authors: Yoshimura Kazuhiro , Nakano Shunji , Tsuruta Daisuke , Ohata Chika , Hashimoto Takashi
Published: April 2013

Plasma cell cheilitis is a chronic inflammatory disease that presents with erythema, erosions, ulcers and occasional nodules within the mucosa, including the lips. It is histopathologically characterized by dense plasma cell infiltration in the lamina propria of the mucous membranes. Several treatments for plasma cell cheilitis have been reported, including topical steroids, topical antibiotics or topical tacrolimus. However, 308‐nm monochromatic excimer light (MEL) has never been reported as a treatment option, while it was reported to be very effective in treating erosive oral lichen planus. We report a 62‐year‐old man who had chronic plasma cell cheilitis on the lower lip, which was refractory to topical and systemic corticosteroid. The lesion and severe pain were significantly improved by the treatment with nine sessions of 308‐nm MEL twice per week with a total dose of 1120 mJ/cm2. However, the lesion gradually worsened after treatment frequency was reduced to once per month. Subsequent tacrolimus 0.03% ointment cleared the lesion completely in a month and no recurrence was observed a year later. Refractory plasma cell cheilitis and concomitant severe pain quickly responded to 308‐nm MEL when administrated twice per week. Because the long interval between each MEL treatment seemed ineffective to improve the lesion, appropriate frequency and adequate total dose of MEL treatment may be necessary for a successful treatment.
Improvement of the sentinel lymph node detection rate of cervical sentinel lymph node biopsy using real‐time fluorescence navigation with indocyanine green in head and neck skin cancer
Authors: Nakamura Yasuhiro , Fujisawa Yasuhiro , Nakamura Yoshiyuki , Maruyama Hiroshi , Furuta Jun‐ichi , Kawachi Yasuhiro , Otsuka Fujio
Published: April 2013

The standard technique using lymphoscintigraphy, blue dye and a gamma probe has established a reliable method for sentinel node biopsy for skin cancer. However, the detection rate of cervical sentinel lymph nodes (SLN) is generally lower than that of inguinal or axillary SLN because of the complexity of lymphatic drainage in the head and neck region and the “shine‐through” phenomenon. Recently, indocyanine green fluorescence imaging has been reported as a new method to detect SLN. We hypothesized that fluorescence navigation with indocyanine green in combination with the standard technique would improve the detection rate of cervical sentinel nodes. We performed cervical sentinel node biopsies using the standard technique in 20 basins of 18 patients (group A) and using fluorescence navigation in combination with the standard technique in 12 basins of 16 patients (group B). The mean number of sentinel nodes was two per basin (range, 1–4) in group A and three per basin (range, 1–5) in group B. The detection rate of sentinel nodes was 83% (29/35) in group A and 95% (36/38) in group B. The false‐negative rate was 6% (1/18 patients) in group A and 0% in group B. Fluorescence navigation with indocyanine green may improve the cervical sentinel node detection rate. However, greater collection of data regarding the usefulness of cervical sentinel node biopsy using indocyanine green is necessary.
CAP Reform and Innovation: The Role of Learning and Innovation Networks
Authors: Brunori Gianluca , Barjolle Dominique , Dockes Anne‐Charlotte , Helmle Simone , Ingram Julie , Klerkx Laurens , Moschitz Heidrun , Nemes Gusztáv , Tisenkopfs Talis
Published: April 2013

CAP Reform and Innovation: The Role of Learning and Innovation Networks

The technological and organisational solutions the agricultural sector has undertaken in the past are not always compatible with the constraints and opportunities that the rural economy and society will face in the future. There is growing agreement that the goal of sustainability cannot be fulfilled without a profound change in the way the economy is organised. Innovation policies are among the most suitable instruments for this purpose. The article, based on the SOLINSA conceptual framework, adopts a network approach to innovation policies. Based on empirical evidence collected from case studies across Europe in the first phase of the project, the paper proposes the concept of Learning and Innovation Networks for Sustainable Agriculture (LINSA). LINSA are defined as ‘networks of producers, customers, experts, Non‐Governmental Organisations, Small and Medium Enterprises, local administrations and components of the formal Agricultural Knowledge System (AKS), that are mutually engaged with common goals for sustainable agriculture and rural development – cooperating, sharing resources and co‐producing new knowledge by creating conditions for communication'. The article proposes that LINSA be considered as policy devices – in line with the European Innovation Partnership initiative – to foster innovation in the direction of sustainability goals as advocated by Europe 2020 strategy.
How Nanotechnologies Can Contribute to Innovation in Food Firms in Europe
Authors: Nardone Gianluca , Seccia Antonio , Maruotti Giuseppina
Published: April 2013

summary

How Nanotechnologies Can Contribute to Innovation in Food Firms in Europe

The possibility of nanotechnologies being introduced in the food industry in a profound way depends on many factors. These include how they meet the demand for innovation made by firms together with acceptance by final consumers as well as the ability of the technological transfer system to reduce the cognitive distance between users and providers. Our discussion indicates that nanotechnologies are able to fulfill different needs of food firms, especially with respect to improving food safety and sensory features. However, their deployment has raised public concerns on ethical and societal issues that are still to be investigated and, in many cases, regulated. Finally, given that nanotechnologies represent a domain with significant knowledge asymmetries and that the food industry has a relatively low absorptive capacity, this presents a good opportunity for innovation brokers to promote technology transfer. The theoretical framework that lies behind this article is a useful instrument to narrow specific cognitive distances to facilitate matching demand and supply of innovative nanotechnologies. It also provides for a better comprehension of the technological paradigm and analysis of consumer acceptance, and draws attention to the necessity of stricter regulations for improving acceptance by consumers.
Agri‐food Innovation and the Functional Food Market in Europe: Concerns and Challenges
Authors: Annunziata Azzurra , Vecchio Riccardo
Published: April 2013

summary

Agri‐food Innovation and the Functional Food Market in Europe: Concerns and Challenges

Europe has recently experienced an increase in several chronic diseases linked to dietary and lifestyle habits. As a result, enormous progress has been made to establish the scientific basis for food developments in the areas of health, nutrition and processing. The food industry has rapidly reacted to this trend by developing a growing variety of new products with health‐related claims and images, including functional foods that are selected by consumers for their health‐promoting properties. The European markets for functional foods are less developed in general than those in North America and Japan. This has often been ascribed to an inconsistent legislation and there is a broad consensus that there is a need for a regulatory framework in the European Union to protect consumers, promote fair trade, and encourage product innovation in the food industry. This article reviews the regulatory aspects of functional foods in Europe and offers an overview of the current market situation. Moreover, the main cognitive, motivational and attitudinal determinants of consumer acceptance of functional foods in different European countries are discussed, providing several practical insights. The insights presented could help practitioners make more effective strategic and tactical marketing decisions.
Principles of transcriptome analysis and gene expression quantification: an RNA‐seq tutorial
Authors: Wolf Jochen B. W.
Published: April 2013

Genome‐wide analyses and high‐throughput screening was long reserved for biomedical applications and genetic model organisms. With the rapid development of massively parallel sequencing nanotechnology (or next‐generation sequencing) and simultaneous maturation of bioinformatic tools, this situation has dramatically changed. Genome‐wide thinking is forging its way into disciplines like evolutionary biology or molecular ecology that were historically confined to small‐scale genetic approaches. Accessibility to genome‐scale information is transforming these fields, as it allows us to answer long‐standing questions like the genetic basis of local adaptation and speciation or the evolution of gene expression profiles that until recently were out of reach. Many in the eco‐evolutionary sciences will be working with large‐scale genomic data sets, and a basic understanding of the concepts and underlying methods is necessary to judge the work of others. Here, I briefly introduce next‐generation sequencing and then focus on transcriptome shotgun sequencing (RNA‐seq). This article gives a broad overview and provides practical guidance for the many steps involved in a typical RNA‐seq work flow from sampling, to RNA extraction, library preparation and data analysis. I focus on principles, present useful tools where appropriate and point out where caution is needed or progress to be expected. This tutorial is mostly targeted at beginners, but also contains potentially useful reflections for the more experienced.
Up regulation of serum tumor necrosis factor‐related apoptosis inducing ligand in juvenile‐onset systemic lupus erythematosus: relations with disease activity, antibodies to double ‐stranded DNA, nephritis and neutropenia
Authors: Ezzat Mohamed H. M. , EL‐Gammasy Tarek M. A. , Shaheen Kareem Y. A. , EL‐Mezdawi Ramzi A. M. , Youssef Mervat S. M.
Published: April 2013

Objectives

Apoptosis is induced by binding of death receptor ligands, members of the tumor necrosis factor (TNF) superfamily, to their cognate receptors. It is suggested that TNF‐related apoptosis inducing ligand (TRAIL) is involved in pathogenesis of juvenile‐onset systemic lupus erythematosus (JSLE). This study aimed to assess TRAIL concentrations in sera of JSLE children and to determine their potential relationship with disease activity, anti‐double‐stranded DNA (anti‐dsDNA) levels, neutropenia and renal involvement.

Methods

Circulating levels of TRAIL were measured by enzyme‐linked immunosorbent assay (ELISA) in serum samples obtained from 40 JSLE patients (20 with active and 20 with inactive disease) and 20 controls.

Results

The mean (SEM) serum TRAIL concentration in JSLE was 1750.7 (440.2) pg/mL. Serum TRAIL concentrations in patients were higher than those in controls (P < 0.01). Serum TRAIL concentrations for children with inactive disease (1854.8 [485.4] pg/mL) and those with activity (1646.6 [390.6] pg/mL) were statistically comparable. JSLE children with positive anti‐dsDNA antibodies had significantly higher TRAIL levels (mean = 1846 [456] vs. 1455 [325] pg/mL; P < 0.05). Serum TRAIL concentrations were significantly higher in classes III and IV nephritis compared to classes I and II nephritis (1970 [512] vs. 1330 [331] pg/mL; P < 0.01). Serum TRAIL concentrations in patients with neutropenia were higher than those without neutropenia (1805 [505] vs. 1516 [400] pg/mL; P = 0.042) and in controls (P = 0.024).

Conclusions

Our data indicate that an increased level of TRAIL is a feature of JSLE that correlates with disease activity, anti‐dsDNA titers neutropenia and lupus nephritis.
Neuroprotective role of γ‐enolase in microglia in a mouse model of Alzheimer's disease is regulated by cathepsin X
Authors: Hafner Anja , Glavan Gordana , Obermajer Nataša , Živin Marko , Schliebs Reinhard , Kos Janko
Published: April 2013

γ‐Enolase is a neurotrophic‐like factor promoting growth, differentiation, survival and regeneration of neurons. Its neurotrophic activity is regulated by cysteine protease cathepsin X which cleaves the C‐terminal end of the molecule. We have investigated the expression and colocalization of γ‐enolase and cathepsin X in brains of Tg2576 mice overexpressing amyloid precursor protein. In situ hybridization of γ‐enolase and cathepsin X revealed that mRNAs for both enzymes were expressed abundantly around amyloid plaques. Immunostaining demonstrated that the C‐terminally cleaved form of γ‐enolase was present in the immediate plaque vicinity, whereas the intact form, exhibiting neurotrophic activity, was observed in microglia cells in close proximity to senile plaque. The upregulation of γ‐enolase in microglial cells in response to amyloid‐β peptide (Aβ) was confirmed in mouse microglial cell line EOC 13.31 and primary microglia and medium enriched with γ‐enolase proved to be neuroprotective against Aβ toxicity; however, the effect was reversed by cathepsin X proteolytic activity. These results demonstrate an upregulation of γ‐enolase in microglia cells surrounding amyloid plaques in Tg2576 transgenic mice and demonstrate its neuroprotective role in amyloid‐β‐related neurodegeneration.
AUDIT‐C Scores as a Scaled Marker of Mean Daily Drinking, Alcohol Use Disorder Severity, and Probability of Alcohol Dependence in a U.S. General Population Sample of Drinkers
Authors: Rubinsky Anna D. , Dawson Deborah A. , Williams Emily C. , Kivlahan Daniel R. , Bradley Katharine A.
Published: April 2013

Background

Brief alcohol screening questionnaires are increasingly used to identify alcohol misuse in routine care, but clinicians also need to assess the level of consumption and the severity of misuse so that appropriate intervention can be offered. Information provided by a patient's alcohol screening score might provide a practical tool for assessing the level of consumption and severity of misuse.

Methods

This post hoc analysis of data from the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) included 26,546 U.S. adults who reported drinking in the past year and answered additional questions about their consumption, including Alcohol Use Disorders Identification Test—Consumption questionnaire (AUDIT‐C) alcohol screening. Linear or logistic regression models and postestimation methods were used to estimate mean daily drinking, the number of endorsed alcohol use disorder (AUD) criteria (“AUD severity”), and the probability of alcohol dependence associated with each individual AUDIT‐C score (1 to 12), after testing for effect modification by gender and age.

Results

Among eligible past‐year drinkers, mean daily drinking, AUD severity, and the probability of alcohol dependence increased exponentially across increasing AUDIT‐C scores. Mean daily drinking ranged from < 0.1 to 18.0 drinks/d, AUD severity ranged from < 0.1 to 5.1 endorsed AUD criteria, and probability of alcohol dependence ranged from < 1 to 65% across scores 1 to 12. AUD severity increased more steeply across AUDIT‐C scores among women than men. Both AUD severity and mean daily drinking increased more steeply across AUDIT‐C scores among younger versus older age groups.

Conclusions

Results of this study could be used to estimate patient‐specific consumption and severity based on age, gender, and alcohol screening score. This information could be integrated into electronic decision support systems to help providers estimate and provide feedback about patient‐specific risks and identify those patients most likely to benefit from further diagnostic assessment.
Microheterogeneity of Serum β‐Hexosaminidase in Chronic Alcohol Abusers in a Driver's License Regranting Program
Authors: Maenhout Thomas M. , Poll Anneleen , Wuyts Birgitte , Lecocq Elke , Van Vlierberghe Hans , De Buyzere Marc L. , Delanghe Joris R.
Published: April 2013

Background

Carbohydrate‐deficient transferrin (CDT) is one of the best indicators for chronic alcohol abuse and detection of relapse. In this study, we explore the microheterogeneity of β‐hexosaminidase (β‐HEX) in chronic alcohol abusers in the framework of a driver's license regranting program. Studies have shown that increased serum activity of β‐HEX B (isoforms P, I, and B) may be a sensitive marker for chronic alcohol abuse. Here, we describe methodology, limitations, and correlation of β‐HEX isoforms with CDT.

Methods

CDT was assayed at the central laboratory of the Ghent University Hospital by capillary zone electrophoresis, measured on the Capillarys 2™ system and was expressed as a percentage of total serum transferrin (%CDT). Serum of chronic alcohol abusers was compared to nonheavy drinkers using agarose gel isoelectric focusing (IEF). Total β‐HEX activity was assayed fluorimetrically following preparative IEF in 81 subjects. β‐HEX isoforms were investigated and compared between nonheavy drinkers and heavy drinkers.

Results

Agarose gel IEF shows additional cathodal bands in serum of chronic alcohol abusers. Mean total β‐HEX activity between pH 6.8 and 7.7, designated as HEX‐7, showed the highest correlation with %CDT (r = 0.70, p < 0.0001, n = 68). In a selected subgroup, where CDT could not be quantified (n = 13) because of an atypical electropherogram, HEX‐7 was in concordance with either estimated %CDT value or liver enzyme activities.

Conclusions

In this proof‐of‐concept study, we introduce a novel approach to quantify β‐HEX isoforms using preparative IEF and fluorimetry. A highly significant correlation of HEX‐7 and %CDT has been found. Because of exclusion of the P isoform, HEX‐7 could be a useful supplementary marker for detecting chronic alcohol abuse.
Double‐blind, placebo‐controlled, dose‐ranging study of new recombinant hypoallergenic Bet v 1 in an environmental exposure chamber
Authors: Meyer W. , Narkus A. , Salapatek A. M. , Häfner D.
Published: April 2013

Background

Recombinant allergens offer a tool for improving specific immunotherapy (SIT).

Objective

To find the optimal dose of a new hypoallergenic folding variant of recombinant Bet v 1 (rBet v 1‐FV) as SIT for patients with birch pollen allergy.

Methods

Before SIT, thirty‐seven adult patients were exposed for eight hours in an environmental exposure chamber (EEC) to birch pollen at an average concentration of 3500 ± 500 grains/m3, then randomized to four maintenance dose groups of rBet v 1‐FV and one placebo group: 20 μg (n = 7), 80 μg (n = 8), 160 μg (n = 7), 320 μg (n = 8), and placebo (n = 7). Patients were treated for 10 weeks with weekly injections and then re‐exposed in the EEC. The optimal dose for SIT was assessed using efficacy results from the EEC, IgG responses, and tolerability.

Results

Thirty‐six patients were evaluable for efficacy assessment. The total symptom score significantly decreased in all active groups compared with placebo (−18.8% for placebo patients; −71.9%, P = 0.0022 for 20 μg; −75.6%, P = 0.0007 for 80 μg; −81.8%, P = 0.0009 for 160 μg; −78.3%, P = 0.0003 for 320 μg). IgG1 increased significantly in all active groups compared to placebo. All four active doses were well tolerated, no serious adverse event occurred; two Grade II reactions, according to EAACI classification, were observed, one in each of the 160‐ and 320‐μg groups.

Conclusions

Considering efficacy, immunological response, and tolerability, a maintenance dose of 80 μg of rBet v 1‐FV appears to be the ideal dose for allergen immunotherapy in birch pollen allergic patients.
Activation of basophils by the double‐stranded RNA poly(A:U) exacerbates allergic inflammation
Authors: Ramadan A. , Pham Van L. , Machavoine F. , Dietrich C. , Alkan M. , Karasuyama H. , Schneider E. , Dy M. , Thieblemont N.
Published: April 2013

Background

It is commonly acknowledged that asthma is exacerbated by viral infections. On the other hand, basophil infiltration of lung tissues has been evidenced postmortem in cases of fatal disease, raising the question of a possible link between these two observations.

Objectives

Herein, we addressed the relationship between asthma exacerbation by viral infection and basophil activation and expansion by investigating how stimulation with the dsRNA polyadenylic/polyuridylic acid [poly(A:U)] affected basophil activities and recruitment in an allergic airway inflammation model.

Methods

The effect of dsRNA on basophils was assessed by measuring the cytokine levels produced upon stimulation. We used an OVA‐induced experimental model of allergic asthma. Airway hyperreactivity, recruitment of infiltrating cells, and cytokine production were determined in the lung of mice having received poly(A:U), as compared with untreated controls. The exacerbating effect of basophils was assessed both by adoptive transfer of poly(A:U)‐treated basophils and by their in vivo depletion with Ba103 antibody.

Results

We found that in vitro treatment with poly(A:U) increased basophil functions by inducing TH2‐type cytokine and histamine production, whereas in vivo treatment increased peripheral basophil recruitment. Furthermore, we provide the first demonstration for increased infiltration of basophils in the lung of mice suffering from airway inflammation. In this model, disease symptoms were clearly exacerbated upon adoptive transfer of basophils exposed to poly(A:U), relative to their unstimulated counterpart. Conversely, in vivo basophil depletion alleviated disease syndromes, thus validating the transfer data.

Conclusions

Our findings provide the first evidence for airway inflammation exacerbation by basophils following dsRNA stimulation.
Interleukin (IL)‐31 activates signal transducer and activator of transcription (STAT)‐1, STAT‐5 and extracellular signal‐regulated kinase 1/2 and down‐regulates IL‐12p40 production in activated human macrophages
Authors: Kasraie S. , Niebuhr M. , Werfel T.
Published: April 2013

Background

Interleukin‐31 is a cytokine expressed by activated T cells. A major function of IL‐31 in atopic dermatitis (AD) is the induction of pruritus in the skin. We recently showed that IL‐31 induces pro‐inflammatory cytokines following staphylococcal exotoxins’ stimulation in human macrophages. However, signalling pathways of IL‐31 in activated human macrophages still remain unclear. The aim of the study was to investigate the signalling pathways of IL‐31 receptor as well as functional effects of IL‐31 in activated macrophages.

Methods

Human macrophages were prestimulated with staphylococcal exotoxins (SEB, α‐toxin) to up‐regulate the IL‐31 receptor with and without IL‐31. Phospho‐signal transducer and activator of transcription (pSTAT) 1/3/5, phospho‐extracellular signal‐regulated kinase (ERK 1/2), β‐actin as well as p21/WAF/Cip1 levels were determined by means of Western blot analysis. Interleukin‐12p40, IL‐12p70 and IL‐23 secretions were assessed by using an enzyme‐linked immunosorbent assay.

Results

Interleukin‐31 strongly activated STAT‐1 and 5 but not STAT‐3 in human macrophages after up‐regulation of IL‐31 receptor with staphylococcal exotoxins. p21/WAF/Cip1 expression was induced by IL‐31 in activated human macrophages. Furthermore, IL‐31 down‐regulated. IL‐12p40 secretion via ERK 1/2 phosphorylation in human macrophages following up‐regulation of IL‐31 receptor with staphylococcal exotoxins.

Conclusions

The T helper (Th) 2 cytokine IL‐31 induces pro‐inflammatory effects in activated human macrophages via STAT‐1 and 5 phosphorylation. Interleukin‐31‐induced ERK 1/2 activation contributes to the underlying mechanism of Th1 cytokine IL‐12 suppression in macrophages. This mechanism may be relevant in Th2 inflammatory responses and may help to develop therapeutic strategies in IL‐31‐associated diseases such as AD.
Effect of hypoxia exposure on the phenotypic adaptation in remodelling skeletal muscle submitted to functional overload
Authors: Chaillou T. , Koulmann N. , Meunier A. , Malgoyre A. , Serrurier B. , Beaudry M. , Bigard X.
Published: April 2013

Aim

To determine whether hypoxia influences the phenotypic adaptation of skeletal muscle induced by mechanical overload.

Methods

Plantaris muscles of female rats were submitted to mechanical overload following synergist ablation. After 3 days of overload, rats were exposed to either hypobaric hypoxia (equivalent to 5500 m) or normoxia. Muscles were collected after 5, 12 and 56 days of overload (i.e. after 3, 9 and 53 days of hypoxia). We determined the myosin heavy chain (MHC) distribution, mRNA levels of myocyte‐enriched calcineurin‐integrating protein 1 (MCIP1) to indirectly assess calcineurin activity, the changes in oxidative capacity from the activities of citrate synthase (CS) and cytochrome c oxidase (COX), and the expression of regulators involved in mitochondrial biogenesis (Pgc‐1α, NRF1 and Tfam) and degradation (BNIP‐3).

Results

Hypoxia did not alter the fast‐to‐slow MHC shift and the increase in calcineurin activity induced by overload; it only transiently slowed down the overload‐induced transition in MHC isoforms. Hypoxia similarly decreased CS and COX activities in overloaded and control muscles. Nuclear respiratory factor 1 (NRF1) and transcription factor A (Tfam) mRNA and BNIP‐3 protein were not influenced by hypoxia in overloaded muscles, whereas Pgc‐1α mRNA and protein contents did not correlate with changes in oxidative capacity.

Conclusion

Hypoxia is not a critical stimulus to modulate the fast‐to‐slow MHC transition associated with overload. Thus, the impairment of the fast‐to‐slow fibre shift often observed during post‐natal development in hypoxia could be explained by the lower voluntary locomotor activity associated with hypoxia. Hypoxia alters mitochondrial oxidative capacity, but this adaptive response is similar in overloaded and control muscles.