bluuebunny/crossref_metadata_2025 huggingface dataset:
How Can Marketing Academics Serve Marketing Practice? The New Marketing DNA as a Model for Marketing Education
Authors: Harrigan Paul , Hulbert Bev
Published: September 2011

This article seeks to address how marketing academics can best serve marketing practice through marketing education. It is contended that, where technology is driving marketing in practice, it is afforded significantly less attention in both theory and education. Thus, the marketing graduates being produced from universities are often lacking in the skills that 21st-century marketers require. Where the focus of the article is on marketing education, a broad analysis of the content of marketing textbooks and degree programs is presented and an “old Marketing DNA” presented. The study also adopted an inductive approach to data collection where the aim was to investigate the exact nature, constituency, and role of marketing in organizations. Qualitative in-depth interviews were undertaken with senior marketing managers and executives in U.K. organizations. Findings are organized into the areas of customer-led marketing, value-driven strategic marketing, channels, data-driven marketing, and online and off-line integrated marketing communications. The article concludes that there is a disconnect between marketing education and marketing practice and goes some way to recommending what the response of marketing academia should be through the “new Marketing DNA.” This article aims to inspire a holistic response from marketing educators to bring their practice more in line with what is actually being practiced by marketing practitioners in the 21st century.
Marketing Capstone Models The Apprentice Television Show With Client-Sponsored Projects
Authors: Strauss Judy
Published: September 2011

Marketing faculty use cases, simulations, and client-sponsored projects to achieve learning objectives in the marketing capstone class. This class typically aims to integrate and apply previously learned material and to transition students into their careers. Drawing on the professional school, creative problem solving and constructivist learning literature, this article describes a unique client-sponsored project capstone patterned after the popular television show, The Apprentice. Student teams accomplish a series of four challenges and their grades partially depend on actual results or the teams’ competitive rankings as judged by clients. There are no exams, lectures, and little assigned reading in this class: Instead, students must determine what they need to learn in order to solve each challenge and the instructor serves as coach and learning facilitator. The class engages and motivates students by providing real-world problems in a short time frame, and develops their creative problem solving, presentation, time management, and team work skills. Although cases and simulations can increase creative problem-solving skills, client-sponsored projects are more easily framed in the ambiguous manner needed to stimulate creative thinking. This article describes the class in detail, outlining sample projects and discussing some of the challenges with client-sponsored projects.
A Decade of Scholarship in Marketing Education
Authors: Abernethy Avery M. , Padgett Daniel
Published: September 2011

The teaching environment in business schools has changed dramatically over the last decade. But the last comprehensive review of the scholarship of teaching was conducted more than a decade ago. Where and from whom do the best practices for teaching originate today? To answer this question, the authors examine marketing education scholarship between 2000 and 2009 by assessing individual and institutional productivity in the two primary marketing education journals, Journal of Marketing Education and Marketing Education Review. Past findings that the most productive institutions for marketing education research were concentrated in the South no longer hold. In the last decade, interest in marketing education research is found at a large number of schools with most authors appearing only once in the two primary marketing education journals and most institutions having only one or two appearances. Higher levels of research productivity appear to be related to institutional mission.
Faraway Intimate Development
Authors: Miraftab Faranak
Published: September 2011

This multisited global ethnography concerns the intimate and unequal relationships that connect revitalization of a Midwestern packing town to development processes in immigrant workers’ communities of origin in Togo and Mexico. It brings to light how immigrants’ families, friends, and home institutions subsidize reproduction of people and place in immigrants’ communities of destination—complex processes and practices I call global restructuring of social reproduction. Revealing the immigration-based nature of local development not only in Mexico and Togo but also in the United States, the study makes visible the global interconnections in processes of dispossession and development.
Sales work and the situated constitution of legitimate economic exchange
Authors: Darr Asaf
Published: September 2011

The legitimacy of economic transactions is a fundamental element of market order, and its constitution facilitates the ongoing exchange of commodities and services. By bringing sales work to centre stage, this study empirically examines the theoretical claim that legitimacy in advanced markets is constituted not only by macro-structures and institutions, but also in the course of sales encounters. Based on 50 interviews and on extensive observations of sales interactions in a computer store, this study presents empirical support to the theoretical claim that legitimate economic exchange is forged by an interactive dialogue between two distinct paradigms which co-exist on the sales floor: one based on market logic and the other on moral arguments. The article calls for an analytic framework for the study of economic action which transcends the rational-irrational dichotomy and which can account for the diverse interests and scripts of behaviour played out on the sales floor.
Mobile central eastern Europeans in Britain: successful European Union citizens and disadvantaged labour migrants?
Authors: Ciupijus Zinovijus
Published: September 2011

Since European Union (EU) enlargement in 2004, over a million mobile central eastern Europeans (CEEs) have found employment in Britain. This unprecedented wave of labour mobility could be interpreted equally as labour migration and as an exercise of the right of freedom of movement extended by EU citizenship. While recognising that the newly acquired freedom of movement has improved the mobility rights of CEEs and showing how CEE workers take advantage of EU citizenship, the analysis reveals the diverging trajectories of spatial and labour market mobilities.
A matter of culture and cost? A comparison of the employment decisions made by mothers with a lower, intermediate and higher level of education in the Netherlands
Authors: Cloïn Mariëlle , Keuzenkamp Saskia , Plantenga Janneke
Published: September 2011

This article is focused on financial-economic and socio-cultural factors in explaining differences in labour participation and working hours of Dutch mothers with diverging educational levels. The data used are taken from a survey held among approximately 1700 women in the Netherlands from two-parent households with children up to 12 years old. The models for participation and working hours are simultaneously estimated for different levels of education. It is found that socio-cultural factors have slightly more impact on the employment decisions of lower educated mothers compared to their higher educated counterparts, although the differences are only minor. Despite the level of education, socio-cultural factors appear to be more important in mothers’ employment decisions than financial-economic factors. In addition, both factors are better predictors for mothers’ decisions to participate than for their number of working hours; demographic variables are found to be the most important predictor for mothers’ working hours.
Work environment quality: the role of workplace participation and democracy
Authors: Knudsen Herman , Busck Ole , Lind Jens
Published: September 2011

The article explores how employee participation influences the quality of the work environment and workers’ well-being at 11 Danish workplaces from within six different industries. Both direct participation and representative forms of participation at the workplace level were studied. Statistical as well as qualitative comparative analyses reveal that work environment quality and high levels of participation go hand in hand. Within a typology of participation models the highest level of participation, including strong elements of collective participation, and also the best work environment, measured as ‘psychosocial well-being’, were found at workplaces managed in accordance with democratic principles.
Indian call centre workers: vanguard of a global middle class?
Authors: Murphy Jonathan
Published: September 2011

The article explores how participation in the transnational interactive services industry impacts on the social identifications of Indian call centre workers. The article’s analytical framework builds from Bourdieu’s work on social stratification, contemporary theorizations of aesthetic labour and conceptualizations of the commodification of self as integral to aesthetic labour. The research data are drawn from a large scale survey and in-depth interviews with Indian call centre workers, focusing on their lifestyles and social values. Comparison is made with Indian and international youth cohorts. The research findings demonstrate the extent to which this group has adopted transnational middle class values and lifestyles. The article concludes that Indian call centre workers can be characterized as part of an emergent global middle class sharing common lifestyles and values with their counterparts in western countries.
Social access in the workplace: are ethnographers gossips?
Authors: Carmel Simon
Published: September 2011

This article is intended as a contribution to our understanding of what it means to gain and retain ‘social access’ in workplace ethnography, in particular examining the role of gossip. Several difficulties encountered in attempting to gain such access within a health care setting are analysed – these difficulties having arisen after formal, physical access had been successfully negotiated. The analysis reveals the importance of participation in workplace gossip and the length of time spent in the field as facilitators of social access. The implications of participating in gossip are discussed in relation to the ethics of ethnographic methodology, in particular drawing a distinction from qualitative interviews.
Identity on the line: constructing professional identity in a HR call centre
Authors: Pritchard Katrina , Symon Gillian
Published: September 2011

This article applies insights from the social construction of professional identity to an understanding of the ‘professional service’ call centre representative (CSR). In this case, HR (human resources) practitioners found themselves in a CSR role in a newly constituted HR call centre and this research explores how they then (re-)constructed their role as professionals within this context. Through a longitudinal, ethnographic study, three key constructions are identified through which CSRs made claims for a professional identity: ‘our work is complex’; ‘our work adds value’; and ‘our work is unique’. The analysis highlights that a contemporary concern with re-orienting HR to a strategic role may lead to perceived segregation and the re-negotiation of professional identities vis-a-vis other groups of HR professionals. Overall, this research challenges accepted norms and definitions of both call centre work and professional identity, suggesting that both are contested and localized constructions achieved through identity work.
The determinants of workplace direct participation: evidence from a regional survey
Authors: Gonzalez Menendez María C.
Published: September 2011

Multivariate analysis of survey data for a Spanish region suggests a model of direct participation aimed mostly at workers’ integration within a broadly neo-Tayloristic approach to labour management and pragmatism of unions and managers. These results question dominant perceptions of the determinants of direct participation, especially that direct participation may always be connected to change and that it cannot enhance institutional industrial relations and participation processes. The political system of industrial relations appears to mediate developments.
Explaining career motivation among female doctors in the Netherlands: the effects of children, views on motherhood and work-home cultures
Authors: Pas Berber , Peters Pascale , Eisinga Rob , Doorewaard Hans , Lagro-Janssen Toine
Published: September 2011

The gender imbalance in senior medical positions is often attributed to an alleged lack of motivation on the part of female doctors, especially those with young children. Some researchers argue that an unsupportive work-home culture in the medical workplace also plays a role. This study investigates whether having children (and the age of the youngest child) affects female doctors’ career motivation and whether this relationship is mediated by views on motherhood and the supportiveness of the work-home culture. Cross-sectional data collected on 1070 Dutch female doctors in 2008 indicates that neither having children nor the age of the youngest child significantly affects the career motivation of female doctors. However, views on motherhood and a supportive work-home culture do affect female doctors’ career motivation. Governmental and organizational policies aimed at maternal employment and improving the work-life balance are discussed in terms of their effectiveness in supporting highly educated working women.
‘Gaming is my work’: identity work in internet-hobbyist game workers
Authors: Lee Yu-Hao , Lin Holin
Published: September 2011

Developments in personal information communication technology (ICT) are facilitating opportunities for turning internet-based hobbies into self-employed occupations. Real income can be earned by trading virtual objects and currencies used in massively multiplayer online games – a form of economic activity known as real money trade (RMT). This study focuses on RMT workers as an example of new cyber workers who lack traditional identity sources, such as public workplaces, recognizable company names or association with existing occupations. Through examining their identity work, this study argues that as more people are taking their work and leisure life online, ambiguity has become an important characteristic of these new cyber workers who provide labour service via the internet. Work identities which used to be established collectively and effortlessly now require active identity work to maintain.
Beyond Anti-Muslim Sentiment
Authors: Jia Lile , Karpen Samuel C. , Hirt Edward R.
Published: September 2011

Americans’ opposition toward building an Islamic community center at Ground Zero has been attributed solely to a general anti-Muslim sentiment. We hypothesized that some Americans’ negative reaction was also due to their motivation to symbolically pursue a positive U.S. group identity, which had suffered from a concurrent economic and political downturn. Indeed, when participants perceived that the United States was suffering from lowered international status, those who identified strongly with the country, as evidenced especially by a high respect or deference for group symbols, reported a stronger opposition to the “Ground Zero mosque” than participants who identified weakly with the country did. Furthermore, participants who identified strongly with the country also showed a greater preference for buildings that were symbolically congruent than for buildings that were symbolically incongruent with the significance of Ground Zero, and they represented Ground Zero with a larger symbolic size. These findings suggest that identifying group members’ underlying motivations provides unusual insights for understanding intergroup conflict.
How an Art Theft’s Publicity and Documentation Can Impact the Stolen Object’s Recovery Rate
Authors: Durney Mark
Published: September 2011

This article quantifies the importance of documentation associated with a stolen work of art to its eventual recovery. The article offers an interpretation of statistical evidence related to works of art registered stolen and in some cases recovered on the Art Loss Register’s (ALR) database between 2000-2009. It utilizes the 1874 theft of Bartolomé Esteban Murillo’s altarpiece from the baptistery of the Cathedral of Seville to underscore how a painting’s historical importance, the substantial news coverage that surrounds its theft, and the public’s interest in the cathedral’s tragic loss facilitated its quick recovery. Although in 1874, the painting could not be registered on international stolen art databases, it is evident the amount of documentation written about the historical work and its tragic theft functioned similarly to the databases available to theft victims today.
MUM-1 Expression Differentiates Tumors in the PEComa Family From Clear Cell Sarcoma and Melanoma
Authors: Ferenczi Katalin , Lastra Ricardo R. , Farkas Tunde , Elenitsas Rosalie , Xu Xiaowei , Roberts Shelley , Brooks John S. , Zhang Paul J.
Published: September 2011

PEComas are mesenchymal neoplasms composed of perivascular epithelioid cells (PEC) and include a spectrum of tumors. PEComas and malignant melanoma share common morphological, immunohistochemical, and ultrastructural features, such as epithelioid cell morphology and melanocytic immunophenotype. Melanocytic markers commonly expressed in PEC tumors include HMB-45, Melan-A/MART-1, tyrosinase, microphthalmia transcription factor (MITF), and occasionally, S100. Given this morphological and immunophenotypical overlap, the differential diagnosis between a PEComa and malignant melanoma can represent a challenge. Additional diagnostic difficulty is the differentiation of melanoma and PEComa from clear cell sarcoma that is indistinguishable from melanoma based on the immunohistochemical profile. Recent studies have shown that MUM-1, a known lymphocyte marker shows positive immunostaining in nevi and melanomas, its expression in PEComas and clear cell sarcoma, however, has not been previously addressed. In this study, the authors analyzed MUM-1 expression using immunohistochemistry in PEComas (n = 8), the PEComa family members, angiomyolipomas (n = 13), and clear cell sarcomas (n = 11) and compared the staining pattern with malignant melanomas (n = 25), both primary (n = 14) and metastatic (n = 11). It was found that 92.3% of primary melanomas and 81.3% of metastatic melanomas were MUM-1 positive. In contrast, MUM-1 was only weakly positive in only 25% of PEComas and negative in all angiomyolipomas. MUM-1 expression was noted in 72.7% of clear cell sarcomas. The study demonstrated differential MUM-1 expression between PEComas and other true melanocytic tumors and suggested that the addition of MUM-1 to the usual panel of melanocyte markers could be a helpful adjunctive study to aid in the differential diagnosis between these entities.
Renal Cell Carcinoma With Extensive Oncocytic Features
Authors: Moghadamfalahi Mana , Alatassi Houda
Published: September 2011

Oncocytic features are a hallmark of renal oncocytoma, but can be seen in other renal tumors such as clear cell renal cell carcinoma with granular cells and eosinophilic variant of chromophobe cell tumors. Up to 5% of renal neoplasms are ultimately diagnosed as unclassified renal cell carcinoma with oncocytic features accounting for a significant number of these tumors. Also a recent morphological variant of mucinous tubular and spindle cell carcinoma with oncocytic changes has been described, adding another challenge. Here we report an unusual case of unclassified renal cell carcinoma with extensive oncocytic changes and we discuss the differential diagnosis.
Virtual Electron Microscopy
Authors: Lee King-Chung , Mak Lap-Sam
Published: September 2011

Ultrastructural examination is a time-consuming and tiring process, requiring search for diagnostic features on a low-contrast screen in a dim environment. This article describes a method to circumvent these problems through the creation of a virtual ultrathin slide. This can be achieved by automated capturing of hundreds of images at high magnification and stitching them together into a digital image with a resolution of 4 nm/pixel. The pathologist can then navigate the virtual slide at his/her workstation computer. The image shows good contrast and resolution for diagnostic purposes, and most important, the pathologist can precisely note where the specific ultrastructural features are located. The setup required to implement virtual electron microscopy includes a transmission electron microscope equipped with motorized stage and automated digital image capture function, 2 free software components, self-developed software, and a desktop-grade computer. Besides use in daily diagnosis, virtual electron microscopy can open up many new applications such as undergraduate teaching, pathology resident training, external quality assurance program, and expert consultation.
The Injured and Regenerating Nervous System
Authors: Irintchev Andrey , Schachner Melitta
Published: September 2011

Understanding restricted functional recovery and designing efficient treatments to alleviate dysfunction after injury of the nervous system remain major challenges in neuroscience and medicine. Numerous molecules of potential significance in neural repair have been identified in vitro, but only few of these have proved to be of major importance in vivo up to now. Among the molecules involved in regeneration are several members of the immunoglobulin superfamily, most notably the neural cell adhesion molecules L1, its close homologue CHL1, and NCAM and, in particular, its polysialic acid glycan moiety. Sufficient evidence is now available to justify the statement that these molecules are major players not only in nervous system development but also in the adult during neural repair and synaptic plasticity. Importantly, insights into the functions of these molecules in promoting or inhibiting functional recovery have allowed the design and assessment of therapeutic approaches in animal models of central nervous system injury that could prove to be applicable in clinical settings.
Framing Emerging Technologies
Authors: Donk André , Metag Julia , Kohring Matthias , Marcinkowski Frank
Published: September 2011

Nanotechnology cannot be directly experienced and observed—all that people know about it and their interpretations and opinions are mainly based on information from the mass media. Therefore, this first systematic study of the German media coverage about nanotechnology aims to analyse the media frames of this emerging technology. It comprises a standardized content analysis of nine print media from 2000 to 2008, which shows that the German media framing is predominantly very positive, specifically emphasizing the medical and economic benefits of nanotechnology. There is hardly any critical coverage opposing this one-sided perspective of progress. This result corresponds to the international media coverage.
Communicative Aspects of the Public-Science Relationship Explored
Authors: Dijkstra Anne M. , Gutteling Jan M.
Published: September 2011

Communication and the way this communication process is perceived by different publics is part of the public-science relationship. This article presents qualitative data with respect to biotechnology and genomics communication and identifies similarities and differences among publics in various roles. Focus group discussions were conducted with members of the general public, active consumers, patients, and genomics experts in the Netherlands. The analysis demonstrated that these publics prefer varied communication approaches that depend on their particular roles, with varying possibilities of participation. In all cases, transparency and openness as basic communication elements have to be fulfilled to gain trust from these publics.
The Intersection of Long-Term Care and End-of-Life Care
Authors: Huskamp Haiden A. , Kaufmann Christine , Stevenson David G.
Published: September 2011

High-quality end-of-life care is an important component of high-quality long-term care, yet many elderly individuals receiving long-term care services do not obtain good care as they approach death. This study provides a systematic review of articles that describe care received at the nexus of long-term care and end-of-life care. The articles identified three primary types of barriers to high-quality end-of-life care in long-term care settings: delivery system barriers intrinsic to long-term care settings, barriers related to features of coverage and reimbursement, and barriers resulting from the current regulatory approach for long-term care providers. The authors recommend areas for future research that would help to support progress on public policy that governs the provision of care at this important intersection.
Polarized Politics and Citizen Disengagement
Authors: Hussey Laura S.
Published: September 2011

This article examines citizens who combine liberalism on one of two major issue dimensions with conservatism on the other, assessing whether they are less politically engaged than “consistent” liberals and conservatives and whether this relationship has strengthened over time with elite polarization. It also explores the contributions of cross-pressures, partisanship, and alienation to contemporary ideological differences in political engagement. This article departs from most existing research by defining ideology two dimensionally. Using the 1984-2008 American National Election Studies, it finds that culturally conservative, economically liberal Americans and to a lesser extent culturally liberal, economically conservative Americans are less engaged in elections than “consistent” liberals and conservatives. Different factors explain these differences with liberals and conservatives, but cross-pressures do not demobilize either “two-dimensional ideologue.” Over time, the increased involvement of liberals and conservatives has produced a growing ideological gap in political engagement.
Pilot Trial of Distributed Constraint-Induced Therapy With Trunk Restraint to Improve Poststroke Reach to Grasp and Trunk Kinematics
Authors: Wu Ching-yi , Chen Yi-an , Chen Hsieh-ching , Lin Keh-chung , Yeh I-ling
Published: September 2011

Background. Constraint-induced therapy (CIT) is effective in improving upper extremity motor function, but evidence is lacking about effectiveness grasp and trunk control. Objective. This study investigated whether distributed CIT combined with trunk restraint (dCIT + TR) benefited movement kinematics of grasping and the trunk, as well as motor ability of the upper extremity, more than dCIT alone. Methods. A total of 45 stroke participants received 2 hours of dCIT + TR, dCIT, or the dose-matched control intervention for 3 weeks. Movement kinematics, motor ability, and daily function were the outcome measures. Movement kinematics included grasping, joint range, and trunk movement at various phases of reach-to-grasp tasks. Motor ability and daily function of all participants were evaluated using the Fugl-Meyer Assessment and the Motor Activity Log. Results. Four to 5 participants in each group were not included for kinematic analysis because of their inability to grasp a can. The dCIT + TR group showed better preplanned grasping movement and less trunk motion at the early phase of the reach-to-grasp movements than the dCIT or control groups. Compared with the controls, the dCIT + TR participants showed better motor ability in the overall and distal arm scores of the Fugl-Meyer Assessment. The dCIT + TR and dCIT participants demonstrated significantly greater functional use of the affected arm. Conclusions. Administering dCIT + TR produced additional benefits by improving grasping control and reversing the compensatory trunk movement at the early phase of a reach-to-grasp movement. The use of experimental tasks beyond and within arm’s length might improve our understanding of optimal upper extremity rehabilitation.
Do Additional Inputs Change Maximal Voluntary Motor Unit Firing Rates After Spinal Cord Injury?
Authors: Zijdewind Inge , Gant Katie , Bakels Rob , Thomas Christine K.
Published: September 2011

Background. Motor unit firing frequencies are low during maximal voluntary contractions (MVCs) of human thenar muscles impaired by cervical spinal cord injury (SCI). Objective. This study aimed to examine whether thenar motor unit firing frequencies increase when driven by both maximal voluntary drive and other concurrent inputs compared with an MVC alone. Methods. Motor unit firing rates, force, and surface electromyographic activity (EMG) were compared across 2 contractions: ( a) MVC alone and ( b) MVC combined with another input (combination contraction). Other inputs (conditions) included vibration, heat, or cold applied to the anterior surface of the forearm, electrical stimulation delivered to the anterior surface of the middle finger, a muscle spasm, or a voluntary contraction of the contralateral thenar muscles against resistance. Results. The maximal firing frequency (n = 68 units), force, and electromyographic activity (n = 92 contraction pairs) were all significantly higher during the combined contractions compared with MVCs alone. There was a 3-way interaction between contraction, condition, and subject for maximal motor unit firing rates, force, and EMG. Thus, combined contraction responses were different for conditions across subjects. Some conditions (eg, a muscle spasm) resulted in more effective and more frequent responses (increases in unit firing frequency, force, EMG in >50% contractions) than others. Recruitment of new units also occurred in combined contractions. Conclusions. Motoneurons are still responsive to additional afferent inputs from various sources when rate modulation from voluntary drive is limited by SCI. Individuals with SCI may be able to combine inputs to control functional tasks they cannot perform with voluntary drive alone.
Acquired Control of Ventral Premotor Cortex Activity by Feedback Training
Authors: Sitaram Ranganatha , Veit Ralf , Stevens Birte , Caria Andrea , Gerloff Christian , Birbaumer Niels , Hummel Friedhelm
Published: September 2011

Background. Despite the availability of various options for movement restoration in stroke patients, there is no effective treatment for patients who show little or no functional recovery of upper limb motor function. Objective. The present study explored the feasibility of real-time functional magnetic resonance imaging brain–computer interface (fMRI-BCI) as a new tool for rehabilitation of this patient population. Methods. Healthy adults and chronic subcortical stroke patients with residual movement were trained for 3 days to regulate the blood oxygenation level dependent (BOLD) response in the ventral premotor cortex (PMv), a secondary motor area with extensive anatomic connections with the primary motor cortex. Effect of learned modulation of the PMv was evaluated with BOLD signal changes across training sessions, transcranial magnetic stimulation (TMS), and a visuomotor task. Results. fMRI-BCI feedback training showed learning with a significantly increasing BOLD signal in the PMv over sessions. Participants’ capability to learn self-regulation was found to depend linearly on intracortical facilitation and correlated negatively with intracortical inhibition measured by TMS prior to feedback training. After training, intracortical inhibition decreased significantly with the volitional increase of the BOLD response in the PMv, indicating a beneficial effect of self-regulation training on motor cortical output. Conclusion. The study provides first evidence for the therapeutic potential of fMRI-BCI in stroke rehabilitation.
Peroxisome proliferator-activated receptors and hepatitis C virus
Authors: Eslam M. , Khattab M. A. , Harrison S. A.
Published: September 2011

The prevalence of type 2 diabetes mellitus and insulin resistance are higher among people chronically infected with hepatitis C (CHC) when compared with the general population and people with other causes of chronic liver disease. Both insulin resistance and diabetes are associated with adverse outcomes across all stages of CHC, including the liver transplant population. CHC is also associated with the development of hepatic steatosis, a common histological feature present in approximately 55% (32–81%) of cases. There is a complex interrelationship between insulin resistance and hepatic steatosis and both are postulated to aggravate each other. The peroxisome proliferator-activated receptors (PPARs) are nuclear factors involved in the regulation of glucose, lipid homeostasis, inflammatory response, cell differentiation, and cell cycle. The relationship between hepatitis C virus replication and PPARs has been the focus of recent study. Given the availability of potent agonists, PPARs may represent a novel pharmacological target in the treatment of CHC.
Therapeutic management options for patients with obscure gastrointestinal bleeding
Authors: Kochhar Gursimran S. , Sanaka Madhusudhan R. , Vargo John J.
Published: September 2011

Obscure gastrointestinal bleeding (OGIB) is one of the most challenging disorders faced by gastroenterologists because of its evasive nature and difficulty in identifying the exact source of bleeding. Recent technological advances such as video capsule endoscopy and small bowel deep enteroscopy have revolutionized the diagnosis and management of patients with OGIB. In this paper, we review the various diagnostic and therapeutic options available for the management of patients with OGIB.
Targeting ion channels for the treatment of gastrointestinal motility disorders
Authors: Beyder Arthur , Farrugia Gianrico
Published: September 2011

Gastrointestinal (GI) functional and motility disorders are highly prevalent and responsible for long-term morbidity and sometimes mortality in the affected patients. It is estimated that one in three persons has a GI functional or motility disorder. However, diagnosis and treatment of these widespread conditions remains challenging. This partly stems from the multisystem pathophysiology, including processing abnormalities in the central and peripheral (enteric) nervous systems and motor dysfunction in the GI wall. Interstitial cells of Cajal (ICCs) are central to the generation and propagation of the cyclical electrical activity and smooth muscle cells (SMCs) are responsible for electromechanical coupling. In these and other excitable cells voltage-sensitive ion channels (VSICs) are the main molecular units that generate and regulate electrical activity. Thus, VSICs are potential targets for intervention in GI motility disorders. Research in this area has flourished with advances in the experimental methods in molecular and structural biology and electrophysiology. However, our understanding of the molecular mechanisms responsible for the complex and variable electrical behavior of ICCs and SMCs remains incomplete. In this review, we focus on the slow waves and action potentials in ICCs and SMCs. We describe the constituent VSICs, which include voltage-gated sodium (NaV), calcium (CaV), potassium (KV, KCa), chloride (Cl–) and nonselective ion channels (transient receptor potentials [TRPs]). VSICs have significant structural homology and common functional mechanisms. We outline the approaches and limitations and provide examples of targeting VSICs at the pores, voltage sensors and alternatively spliced sites. Rational drug design can come from an integrated view of the structure and mechanisms of gating and activation by voltage or mechanical stress.
Screening for celiac disease in average-risk and high-risk populations
Authors: Aggarwal Saurabh , Lebwohl Benjamin , Green Peter H. R.
Published: September 2011

The prevalence of celiac disease is rising. As a result there is increasing interest in the associated mortality and morbidity of the disease. Screening of asymptomatic individuals in the general population is not currently recommended; instead, a strategy of case finding is the preferred approach, taking into account the myriad modes of presentation of celiac disease. Although a gluten-free diet is the treatment of choice in symptomatic patients with celiac disease, there is no consensus on whether institution of a gluten-free diet will improve the quality of life in asymptomatic screen-detected celiac disease patients. A review of the studies that have been performed on this subject is presented. Certain patient groups such as those with autoimmune diseases may be offered screening in the context of an informed discussion regarding the potential benefits, with the caveat that the data on this issue are sparse. Active case finding seems to be the most prudent option in most clinical situations.
A CCR4 antagonist combined with vaccines induces antigen-specific CD8+ T cells and tumor immunity against self antigens
Authors: Pere Helene , Montier Yves , Bayry Jagadeesh , Quintin-Colonna Francoise , Merillon Nathalie , Dransart Estelle , Badoual Cecile , Gey Alain , Ravel Patrice , Marcheteau Elie , Batteux Frederic , Sandoval Federico , Adotevi Olivier , Chiu Christopher , Garcia Sylvie , Tanchot Corinne , Lone Yu-Chun , Ferreira Luis Carlos , Nelson Brad H. , Hanahan Douglas , Fridman Wolf Herman , Johannes Ludger , Tartour Eric
Published: September 2011

Regulatory T cells (Tregs) may impede cancer vaccine efficacy in hematologic malignancies and cancer. CCR4 antagonists, an emergent class of Treg inhibitor, have been shown to block recruitment of Tregs mediated by CCL22 and CCL17. Our aim was to demonstrate the ability of a CCR4 antagonist (a small chemical molecule identified in silico) when combined with vaccines to break peripheral tolerance controlled by Tregs, a prerequisite for the induction of CD8+ T cells against self Ags. Immunization of transgenic or normal mice expressing tumor-associated self Ags (Her2/neu, OVA, gp100) with a CCR4 antagonist combined with various vaccines led to the induction of effector CD8+ T cells and partial inhibition of tumor growth expressing self Ags in both prophylactic and therapeutic settings. The CCR4 antagonist was more efficient than cyclophosphamide to elicit anti-self CD8+ T cells. We also showed that the population of Tregs expressing CCR4 corresponded to memory (CD44high) and activated (ICOS+) Tregs, an important population to be targeted to modulate Treg activity. CCR4 antagonist represents a competitive class of Treg inhibitor able to induce functional anti-self CD8+ T cells and tumor growth inhibition when combined with vaccines. High expression of CCR4 on human Tregs also supports the clinical development of this strategy.
Mutation of L-2,3-diaminopropionic acid synthase genes blocks staphyloferrin B synthesis in Staphylococcus aureus
Authors: Beasley Federico C , Cheung Johnson , Heinrichs David E
Published: September 2011

Background

Staphylococcus aureus synthesizes two siderophores, staphyloferrin A and staphyloferrin B, that promote iron-restricted growth. Previous work on the biosynthesis of staphyloferrin B has focused on the role of the synthetase enzymes, encoded from within the sbnA-I operon, which build the siderophore from the precursor molecules citrate, alpha-ketoglutarate and L-2,3-diaminopropionic acid. However, no information yet exists on several other enzymes, expressed from the biosynthetic cluster, that are thought to be involved in the synthesis of the precursors (or synthetase substrates) themselves.

Results

Using mutants carrying insertions in sbnA and sbnB, we show that these two genes are essential for the synthesis of staphyloferrin B, and that supplementation of the growth medium with L-2,3-diaminopropionic acid can bypass the block in staphyloferrin B synthesis displayed by the mutants. Several mechanisms are proposed for how the enzymes SbnA, with similarity to cysteine synthase enzymes, and SbnB, with similarity to amino acid dehydrogenases and ornithine cyclodeaminases, function together in the synthesis of this unusual nonproteinogenic amino acid L-2,3-diaminopropionic acid.

Conclusions

Mutation of either sbnA or sbnB result in abrogation of synthesis of staphyloferrin B, a siderophore that contributes to iron-restricted growth of S. aureus. The loss of staphyloferrin B synthesis is due to an inability to synthesize the unusual amino acid L-2,3-diaminopropionic acid which is an important, iron-liganding component of the siderophore structure. It is proposed that SbnA and SbnB function together as an L-Dap synthase in the S. aureus cell.
Improving Cry8Ka toxin activity towards the cotton boll weevil (Anthonomus grandis)
Authors: Oliveira Gustavo R , Silva Maria CM , Lucena Wagner A , Nakasu Erich YT , Firmino Alexandre AP , Beneventi Magda A , Souza Djair SL , Gomes José E , de Souza José DA , Rigden Daniel J , Ramos Hudson B , Soccol Carlos R , Grossi-de-Sa Maria F
Published: September 2011

Background

The cotton boll weevil (Anthonomus grandis) is a serious insect-pest in the Americas, particularly in Brazil. The use of chemical or biological insect control is not effective against the cotton boll weevil because of its endophytic life style. Therefore, the use of biotechnological tools to produce insect-resistant transgenic plants represents an important strategy to reduce the damage to cotton plants caused by the boll weevil. The present study focuses on the identification of novel molecules that show improved toxicity against the cotton boll weevil. In vitro directed molecular evolution through DNA shuffling and phage display screening was applied to enhance the insecticidal activity of variants of the Cry8Ka1 protein of Bacillus thuringiensis.

Results

Bioassays carried out with A. grandis larvae revealed that the LC50 of the screened mutant Cry8Ka5 toxin was 3.15-fold higher than the wild-type Cry8Ka1 toxin. Homology modelling of Cry8Ka1 and the Cry8Ka5 mutant suggested that both proteins retained the typical three-domain Cry family structure. The mutated residues were located mostly in loops and appeared unlikely to interfere with molecular stability.

Conclusions

The improved toxicity of the Cry8Ka5 mutant obtained in this study will allow the generation of a transgenic cotton event with improved potential to control A. grandis.
New approach for T-wave end detection on electrocardiogram: Performance in noisy conditions
Authors: Vázquez-Seisdedos Carlos R , Neto João Evangelista , Marañón Reyes Enrique J , Klautau Aldebaro , Limão de Oliveira Roberto C
Published: September 2011

Background

The detection of T-wave end points on electrocardiogram (ECG) is a basic procedure for ECG processing and analysis. Several methods have been proposed and tested, featuring high accuracy and percentages of correct detection. Nevertheless, their performance in noisy conditions remains an open problem.

Methods

A new approach and algorithm for T-wave end location based on the computation of Trapezium's areas is proposed and validated (in terms of accuracy and repeatability), using signals from the Physionet QT Database. The performance of the proposed algorithm in noisy conditions has been tested and compared with one of the most used approaches for estimating the T-wave end point: the method based on the threshold on the first derivative.

Results

The results indicated that the proposed approach based on Trapezium's areas outperformed the baseline method with respect to accuracy and repeatability. Also, the proposed method is more robust to wideband noise.

Conclusions

The trapezium-based approach has a good performance in noisy conditions and does not rely on any empirical threshold. It is very adequate for use in scenarios where the levels of broadband noise are significant.
Nogo receptor is involved in the adhesion of dendritic cells to myelin
Authors: McDonald Claire L , Steinbach Karin , Kern Florian , Schweigreiter Rüdiger , Martin Roland , Bandtlow Christine E , Reindl Markus
Published: September 2011

Background

Nogo-66 receptor NgR1 and its structural homologue NgR2 are binding proteins for a number of myelin-associated inhibitory factors. After neuronal injury, these inhibitory factors are responsible for preventing axonal outgrowth via their interactions with NgR1 and NgR2 expressed on neurons. In vitro, cells expressing NgR1/2 are inhibited from adhering to and spreading on a myelin substrate. Neuronal injury also results in the presence of dendritic cells (DCs) in the central nervous system, where they can come into contact with myelin debris. The exact mechanisms of interaction of immune cells with CNS myelin are, however, poorly understood.

Methods

Human DCs were differentiated from peripheral blood monocytes and mouse DCs were differentiated from wild type and NgR1/NgR2 double knockout bone marrow precursors. NgR1 and NgR2 expression were determined with quantitative real time PCR and immunoblot, and adhesion of cells to myelin was quantified.

Results

We demonstrate that human immature myeloid DCs express NgR1 and NgR2, which are then down-regulated upon maturation. Human mature DCs also adhere to a much higher extent to a myelin substrate than immature DCs. We observe the same effect when the cells are plated on Nogo-66-His (binding peptide for NgR1), but not on control proteins. Mature DCs taken from Ngr1/2 knockout mice adhere to a much higher extent to myelin compared to wild type mouse DCs. In addition, Ngr1/2 knockout had no effect on in vitro DC differentiation or phenotype.

Conclusions

These results indicate that a lack of NgR1/2 expression promotes the adhesion of DCs to myelin. This interaction could be important in neuroinflammatory disorders such as multiple sclerosis in which peripheral immune cells come into contact with myelin debris.
Vascular endothelial growth factor-A and chemokine ligand (CCL2) genes are upregulated in peripheral blood mononuclear cells in Indian amyotrophic lateral sclerosis patients
Authors: Gupta Pawan K , Prabhakar Sudesh , Abburi Chandrika , Sharma Neel K , Anand Akshay
Published: September 2011

Background

We have earlier shown that protein levels of vascular endothelial growth factor-A (VEGF-A) and chemokine ligand-2 (CCL2) were elevated in Indian amyotrophic lateral sclerosis (ALS) patients. Here, we report the mRNA levels of VEGF-A and CCL2 in Indian ALS patients since they display extended survival after disease onset.

Methods

VEGF-A and CCL2 mRNA levels were measured in peripheral blood mononuclear cells (PBMCs) of 50 sporadic Indian ALS patients using Real Time Polymerase Chain Reaction (PCR) and compared with normal controls (n = 50). Their levels were adjusted for possible confounders like cigarette smoking, alcohol and meat consumption.

Results

VEGF-A and CCL2 mRNA levels were found to be significantly elevated in PBMCs in ALS patients as compared to controls. PBMCs from definite ALS revealed higher VEGF-A mRNA expression as compared to probable and possible ALS. CCL2 mRNA levels were found to be unaltered when definite, probable and possible ALS were compared. PBMCs from patients with respiratory dysfunction showed much higher VEGF-A and CCL2 elevation when compared to patients without respiratory dysfunction. No association of smoking, alcohol and meat consumption with VEGF-A and CCL2 was observed after analyzing the data with univariate and multivariate analysis.

Conclusion

VEGF-A and CCL2 mRNA upregulation in PBMCs may have a clinico-pathological/etiological/epidemiological association with ALS pathogenesis. The cross-cultural and cross-ethnic investigations of these molecules could determine if they have any role in enhancing the mean survival time unique to Indian ALS patients.