bluuebunny/crossref_metadata_2025 huggingface dataset:
Private Management and Public Opinion
Authors: Vallentin Steen
Published: August 2007

This article presents a conceptual exploration of public opinion (PO) from the point of view of corporate social responsiveness (CSR2). The proposed PO-CSR2 framework encompasses four complementary means of framing public opinion: the philosophy of measurement of the market view (PO1); the action theory of the mobilization view (PO2); the negative, constraining mode of the social control view (PO3); and the proactive stance of the strategic enactment view (PO4). The article unfolds the particular characteristics of these four views and shows how they, individually and in conjunction, can serve as useful tools for understanding and analyzing corporate social responsiveness. Far from being a narrow concept that focuses attention mainly on the popular—and, some would say, superficial—aspects of responsiveness, the author argues that public opinion is a concept that embodies variety and provides a multifaceted point of departure for reflections on the relationship between business and society.
Reconsidering Teamwork
Authors: Guest Andrew M.
Published: August 2007

Although developing “teamwork” is commonly discussed as a goal for youth work, the meaning of teamwork is rarely articulated. Drawing from field research with programs for children and youth in a Chicago public housing community and with a community of Angolan refugee camps, this article demonstrates that teamwork has multiple potential meanings. The popular meaning, regularly invoked in the media, sports, and business settings and often assumed in youth development settings, focuses on efficient productivity. In the two local communities considered here, however, teamwork often meant prioritizing loyal affiliations or hierarchical social order above and beyond efficient productivity. The author concludes that reflective considerations of developmental competencies, such as teamwork, are important for respecting diverse models of positive youth development.
Examining Social Capital as a Mechanism for Improving School Engagement Among Low Income Hispanic Girls
Authors: Garcia-Reid Pauline
Published: August 2007

Hispanic females are a rapidly growing population and are now considered the largest group of ethnic minority girls in the United States. Yet research to guide their educational needs remains sparse. Addressing this concern, this investigation incorporated a strengths-based approach for examining school engagement among Hispanic middle school girls. A path model predicting school engagement was tested that included a neighborhood environment variable (e.g., neighborhood dangerousness) and variables to assess social capital (e.g., teacher support, friend support, and parent support). The hypothesized model was found to fit data from the sample and showed the positive and direct effects of teacher support, friend support, and parent support on school engagement, and further demonstrated that the perceived absence of neighborhood dangerousness was positively and directly associated with engagement in school. Implications for school-based interventions for Latina youth are discussed.
Supervised exercise training combined with ginkgo biloba treatment for patients with peripheral arterial disease
Authors: Wang Jianxiong , Zhou Shi , Bronks Roger , Graham John , Myers Stephen
Published: August 2007

Objectives: To evaluate whether a combination of supervised exercise training and ginkgo biloba treatment is a better treatment than exercise training alone for patients with peripheral arterial disease.

Design: A 24-week double-blind, placebo-controlled ginkgo biloba trial with the first 12-week period as a non-exercise control stage and the second 12-week period as an exercise training stage.

Setting: Exercise physiology laboratory.

Subjects: Twenty-two subjects with peripheral arterial disease.

Interventions: The subjects were randomly allocated into a ginkgo or a placebo group. During the first stage, the ginkgo group ingested standardized ginkgo biloba tablets with a daily dosage of 240 mg, while the placebo group received placebo tablets. During the second stage, all subjects engaged in a supervised treadmill-walking programme while continuing to take the same dosage of ginkgo biloba or placebo tablets.

Main measures: Walking capacity on treadmill, oxygen consumption during exercise, peripheral haemodynamics and blood viscosity were measured at baseline, and after the first and the second stages of treatment.

Results: The ginkgo group did not show significant changes in most of the measured variables after each stage of treatment, except that the maximal walking time was significantly increased after the combined treatment (from 236 ± 112 seconds to 557 ± 130 seconds, P < 0.001). However, similar response was also found in the placebo group after exercise training (from 384 ± 125 seconds to 820 ± 146 seconds, P < 0.001).

Conclusion: Supervised exercise training combined with ginkgo biloba treatment did not produce greater beneficial effects than exercise training alone in patients with peripheral arterial disease.
Special Section: Rezoning Pleasure
Authors: McIlwain Doris
Published: August 2007

Much contemporary psychological and psychoanalytic research embraces affects but deletes drives. Tomkins made specific place for both affects and drives in his theory, suggesting that much of interest arose from their conflict and co-assembly. This article explores why drives have been dismissed, and argues for their explanatory usefulness in an embodied science of personality. Possible advantages of Tomkins' affect theory over Freud's are discussed as a prelude to assembling (via Westen) a lean, mean, motivational model of personality development. The model combines a view of drives consonant with contemporary evidence and representative of the early Freud with a differential affect theory indebted to Silvan Tomkins. Applications of the model are explored using as case studies personality research on psychopathy and the role of shame in narcissism. The model explores the way that signature personality profiles emerge as developmental pathways are opened or closed due to affective idiosyncrasy.
A statistical modelling approach for the analysis of TMD chronic pain data
Authors: D'Elia Angela
Published: August 2007

This paper presents a discrete mixture model as a suitable approach for the analysis of chronic pain data, when they are expressed by means of ordered scores (ratings). The model is developed to allow for covariates effects; parameters estimation by maximum likelihood (using an E—M algorithm) and related inferential issues are discussed. A case-study concerning the assessment of pain (for a given pathology) and the effect of patients' covariates (e.g., gender, depression state) is illustrated. Besides, the same covariates are considered also for explaining the disruption in everyday lifestyle due to the chronic pain condition.
Evaluation of change in CD4+ cell counts in AIDS clinical trials
Authors: Liang H.
Published: August 2007

To evaluate the antiretroviral activity of antiretroviral agents and to compare the effects of two different antiretroviral agents, we propose a non-parametric mixed-effects model to investigate change of CD4+ counts. The proposed model and methods are applied to analyse the data from PACTG345 study. Population and individual patterns of change of CD4+ counts and a reference band are obtained. Our results indicate that treatment with high-dose ritonavir is significantly superior compared with low-dose ritonavir.
A new efficient statistical test for detecting variability in the gene expression data
Authors: Mathur Sunil , Dolo Samuel
Published: August 2007

DNA microarray technology allows researchers to monitor the expressions of thousands of genes under different conditions. The detection of differential gene expression under two different conditions is very important in microarray studies. Microarray experiments are multi-step procedures and each step is a potential source of variance. This makes the measurement of variability difficult because approach based on gene-by-gene estimation of variance will have few degrees of freedom. It is highly possible that the assumption of equal variance for all the expression levels may not hold. Also, the assumption of normality of gene expressions may not hold. Thus it is essential to have a statistical procedure which is not based on the normality assumption and also it can detect genes with differential variance efficiently. The detection of differential gene expression variance will allow us to identify experimental variables that affect different biological processes and accuracy of DNA microarray measurements.

In this article, a new nonparametric test for scale is developed based on the arctangent of the ratio of two expression levels. Most of the tests available in literature require the assumption of normal distribution, which makes them inapplicable in many situations, and it is also hard to verify the suitability of the normal distribution assumption for the given data set. The proposed test does not require the assumption of the distribution for the underlying population and hence makes it more practical and widely applicable. The asymptotic relative efficiency is calculated under different distributions, which show that the proposed test is very powerful when the assumption of normality breaks down. Monte Carlo simulation studies are performed to compare the power of the proposed test with some of the existing procedures. It is found that the proposed test is more powerful than commonly used tests under almost all the distributions considered in the study. A microarray data is used to illustrate the working of the proposed test. Results indicate that the proposed test is very powerful in detecting the smallest change in differential expression variance with high degree of confidence than some of its competitors.
A Model of Social Interactions and Endogenous Poverty Traps
Authors: Fryer Roland G.
Published: August 2007

This paper develops a model of social interactions and endogenous poverty traps. The key idea is captured in a framework in which the likelihood of future social interactions with members of one's group is partly determined by group-specific investments made by individuals. I prove three main results. First, some individuals expected to make group-specific capital investments are worse off because their observed decision is used as a litmus test of group loyalty — creating a trade-off between human capital and cooperation among the group. Second, there exist equilibria which exhibit bipolar human capital investment behavior by individuals of similar ability. Third, as social mobility increases this bipolarization increases. The model's predictions are consistent with the bifurcation of distinctively black names in the mid-1960s, the erosion of black neighborhoods in the 1970s, accusations of `acting white', and the efficacy of certain programs designed to encourage human capital acquisition.
Measurement of Vertical and Horizontal Idiocentrism and Allocentrism in Small Groups
Authors: Seyyed Babak Alavi  , McCormick John
Published: August 2007

A new conceptual framework of collective orientation in team contexts has recently been proposed in terms of vertical and horizontal dimensions of idiocentrism and allocentrism. A two-phase longitudinal study of 270 university students engaged in 86 academic groups partly confirmed the conceptualization by identifying four interpretable factors: vertical and horizontal idiocentrism, horizontal allocentrism, and avoiding arguments. The results of exploratory and confirmatory factor analyses and a structural model of relationships between the four dimensions in both phases of the study are reported in this article.
Cognitive Styles and Approaches To Studying in Management Education
Authors: Backhaus Kristin , Liff Joshua P.
Published: August 2007

This article examines the role of intuition and/or analysis cognitive styles and approaches to studying in business education. The Cognitive Style Index (CSI) and Revised Approaches to Studying Inventory (RASI) were administered to 222 American undergraduate business students. The authors found a relationship between analytic orientation and grade point average. Furthermore, the authors found a correlation between academic performance and higher scores on the Deep, Strategic, Metacognitive Awareness, and Academic Self-Confidence Scales of the RASI. Women adopted a more analytic style and scored higher on the Surface and Strategic Scales of the RASI. The authors discuss implications of these findings for management education.
A Student-Empowered System for Measuring and Weighing Participation in Class Discussion
Authors: Mainkar Avinash V.
Published: August 2007

Although practiced widely in management education, grading of student participation in class discussions has been criticized by researchers: The instructor simultaneously adopts two incompatible tasks of facilitating class discussion and evaluating student participation; students play for points instead of focusing on learning; and common, instructor-based grading schemes do not motivate all students equally. This article proposes a grading system that addresses these three concerns. The proposed system gives students peer feedback within the domain of participation in class discussion enabling instructors to focus on creating learning opportunities in the classroom. The proposed grading system, with interrater reliability exceeding .80, can easily be modified by individual instructors to suit their teaching styles.
Trust, Control, and Risk
Authors: Şengün Ayşe Elif , Nazli Wasti S.
Published: August 2007

This study investigates the interaction among trust, control, and risk by empirically testing Das and Teng's conceptual framework in a long-term supply agreement following a qualitative study of context. Results suggest that only three model propositions were not supported. Goodwill trust was not related to relational risks, whereas output control and social control were positively related to relational risks and performance risks, respectively. The relationship between trust and social control is complementary, whereas that for trust and output control is substitutive. Goodwill trust is positively related to performance risk taking. Also, output control undermines goodwill and competence trust, whereas social control enhances both types of trust. Goodwill trust and competence trust are positively related to social control. Although goodwill trust decreases the need for output control, competence trust does not. The results suggest that Das and Teng's original model is substantially applicable to the given context.
R&D Alliances and the Effect of Experience on Innovation
Authors: Rubin de Celis Jaime C. , Lipinski John
Published: August 2007

Past success and failure shapes the future decisions of an organization. Recent research shows that experience with previous strategic alliances is an important determinant for new alliances. However, the benefits of past experience depreciate rapidly, and the total number of long-dated experiences does not appear to be a major source of success in dynamic industries. The authors extend Sampson's work to the semiconductor industry to determine the effect of experience on these firms. This article offers an interesting extension to previous studies on experience effects and shows that experience does matter in amount and recency.
Growing the Employee Brand at ASI
Authors: Miles Sandra Jeanquart , Mangold W. Glynn
Published: August 2007

The employee brand is the image presented to an organization's customers and other relevant stakeholders through its employees. The employee branding process is predicated on achieving and maintaining message consistency throughout the organization. Messages emanate from various organizational sources such as the systems of organizational staffing, performance management, and compensation. Each message should reflect and reinforce the organization's desired brand image which, in turn, should be consistent with the organization's mission and values. When this happens, both the psychological contract and employee brand knowledge is effectively managed, resulting in a brand image that is consistent with the organization's desired brand image. The development of the employee brand through the employee branding process can provide a source of sustainable competitive advantage for the organization. This case study is designed to be used as a teaching tool for understanding the complexity of the process and providing guidance for growing the employee brand.
Overqualification and Selection in Leadership Training
Authors: Fine Saul
Published: August 2007

This study examines perceived overqualification in a leadership training scenario. The results show that overqualification is associated with negative attitudes but not with poor performance. General mental ability and the Big Five personality scale of openness to experience are able to predict perceived overqualification ( r = .53) such that individuals in the top 30% of these scores (aggregated) were more than twice as likely to feel overqualified than the rest of the sample. Possible implications for the selection and design of leadership training programs are discussed.
Labor and Capital Taxation with Public Inputs as Common Property
Authors: Feehan James P. , Batina Raymond G.
Published: August 2007

The services of many public inputs (e.g., dams, irrigation systems, and highways) are provided to private firms on a free-access basis. If these services enter constant-returns-to-scale production functions then there are decreasing returns to scale in the private factors. Thus a change in the amount of a public input gives rise to positive rent or economic profit in the first instance. The authors extend the literature by recognizing that this rent cannot be an equilibrium phenomenon. Private agents will engage in rent-seeking that will ultimately lead to dissipation. This makes a public input equivalent to a common property resource, which, in the absence of the appropriate price or quantity rationing, gives rise to inefficiency. Using a model with capital and labor as private inputs, the authors show it is optimal to tax capital even though a labor tax is available and capital is internationally mobile. Production efficiency also holds since our policy supports the first-best equilibrium despite decreasing returns to scale in private inputs.
Respiratory impedance in children with cystic fibrosis using forced oscillations in clinic
Authors: Gangell C. L. , Horak F. , Patterson H. J. , Sly P. D. , Stick S. M. , Hall G. L.
Published: August 2007

Measurement of lung function is an important component of clinical management in cystic fibrosis (CF), but has been difficult in young children. The present study aimed to characterise the utility of the forced oscillation technique for measurement of lung function in preschool-aged children with CF in a routine clinical setting.

Lung function was assessed in 56 young children (aged 2–7 yrs) with CF. Respiratory system resistance (Rrs) and reactance (Xrs) at 6, 8 and 10 Hz were measured and expressed as Z-scores. Children were classified as asymptomatic or symptomatic based on an administered respiratory questionnaire and physical examination at the time of testing. Between-test repeatability was assessed in 25 children.

Measurement of lung function using the forced oscillation technique was feasible in the CF clinic. The children with CF, as a group, had Z-scores forRrsat 6 Hz (Rrs,6)Rrs,8,Rrs,10,Xrsat 6 Hz (Xrs,6) andXrs,8that were significantly different from zero. Children with current symptoms showed significantly decreasedXrsand increasedRrs,6compared with asymptomatic children.

Measurement of lung function using the forced oscillation technique is feasible in young children with cystic fibrosis in a clinical setting. The technique has the potential to improve knowledge concerning early cystic fibrosis lung disease.
Discrimination of exudative pleural effusions based on multiple biological parameters
Authors: Daniil Z. D. , Zintzaras E. , Kiropoulos T. , Papaioannou A. I. , Koutsokera A. , Kastanis A. , Gourgoulianis K. I.
Published: August 2007

Pleural effusion is a common complication of various diseases. Conventional methods are not always capable of establishing the cause of pleural effusion, so alternative tests are needed. The aim of this study was to explore means of discriminating between different pleural effusion groups, malignant, parapneumonic and tuberculous, based on the combined function of seven biological markers.

Adenosine deaminase (ADA), interferon-γ, C-reactive protein (CRP), carcinoembryonic antigen, interleukin-6, tumour necrosis factor-α and vascular endothelial growth factor concentration levels were measured in pleural fluid from 45 patients with malignant, 15 with parapneumonic and 12 with tuberculous pleural effusion. Receiver operating characteristic curve analysis, multinomial logit modelling and canonical variate analysis were applied to discriminate the pleural effusion groups.

The three groups could be discriminated successfully using the measured markers. The most important parameters for discrimination were ADA and CRP concentration levels. An individual with an ADA concentration level of >45 U·L−1and a CRP concentration of <4 mg·dL−1was more likely to belong to the tuberculous pleural effusion group, whereas one with an ADA concentration level of <40 U·L−1and a CRP concentration of >6 mg·dL−1was more likely to belong to the parapneumonic pleural effusion group, and one with a CRP concentration of <4 mg·dL−1to the malignant pleural effusion group.

The combination of adenosine deaminase and C-reactive protein levels might be sufficient for discriminating between the three different groups of exudative pleural effusion: malignant, tuberculous and parapneumonic.
Structural footprinting in protein structure comparison: the impact of structural fragments
Authors: Zotenko Elena , Islamaj Dogan Rezarta , Wilbur W John , O'Leary Dianne P , Przytycka Teresa M
Published: August 2007

Background

One approach for speeding-up protein structure comparison is the projection approach, where a protein structure is mapped to a high-dimensional vector and structural similarity is approximated by distance between the corresponding vectors. Structural footprinting methods are projection methods that employ the same general technique to produce the mapping: first select a representative set of structural fragments as models and then map a protein structure to a vector in which each dimension corresponds to a particular model and "counts" the number of times the model appears in the structure. The main difference between any two structural footprinting methods is in the set of models they use; in fact a large number of methods can be generated by varying the type of structural fragments used and the amount of detail in their representation. How do these choices affect the ability of the method to detect various types of structural similarity?

Results

To answer this question we benchmarked three structural footprinting methods that vary significantly in their selection of models against the CATH database. In the first set of experiments we compared the methods' ability to detect structural similarity characteristic of evolutionarily related structures, i.e., structures within the same CATH superfamily. In the second set of experiments we tested the methods' agreement with the boundaries imposed by classification groups at the Class, Architecture, and Fold levels of the CATH hierarchy.

Conclusion

In both experiments we found that the method which uses secondary structure information has the best performance on average, but no one method performs consistently the best across all groups at a given classification level. We also found that combining the methods' outputs significantly improves the performance. Moreover, our new techniques to measure and visualize the methods' agreement with the CATH hierarchy, including the threshholded affinity graph, are useful beyond this work. In particular, they can be used to expose a similar composition of different classification groups in terms of structural fragments used by the method and thus provide an alternative demonstration of the continuous nature of the protein structure universe.
Development of a workplace intervention for sick-listed employees with stress-related mental disorders: Intervention Mapping as a useful tool
Authors: van Oostrom Sandra H , Anema Johannes R , Terluin Berend , Venema Anita , de Vet Henrica CW , van Mechelen Willem
Published: August 2007

Background

To date, mental health problems and mental workload have been increasingly related to long-term sick leave and disability. However, there is, as yet, no structured protocol available for the identification and application of an intervention for stress-related mental health problems at the workplace. This paper describes the structured development, implementation and planning for the evaluation of a return-to-work intervention for sick-listed employees with stress-related mental disorders (SMDs). The intervention is based on an existing successful return-to-work intervention for sick-listed employees with low back pain.

Methods

The principles of Intervention Mapping were applied to combine theory and evidence in the development, implementation and planning for the evaluation of a participatory workplace intervention, aimed at an early return-to-work for sick-listed employees with SMDs. All stakeholders were involved in focus group interviews: i.e. employees recently sick-listed with SMDs, supervisors and occupational health professionals.

Results

The development of the participatory workplace intervention according to the Intervention Mapping principles resulted in a structured return-to-work intervention, specifically tailored to the needs of sick-listed employees with SMDs. Return-to-work was proposed as a behavioural change, and the Attitude – Social influence – self-Efficacy model was identified as a theoretical framework. Stakeholder involvement in focus group interviews served to enhance the implementation. The cost-effectiveness of the intervention will be evaluated in a randomised controlled trial.

Conclusion

Intervention Mapping was found to be a promising method to develop interventions tailored to a specific target group in the field of occupational health.

Trial registration

ISRCTN92307123
Comparison of disc diffusion, Etest and broth microdilution for testing susceptibility of carbapenem-resistant P. aeruginosa to polymyxins
Authors: van der Heijden Inneke M , Levin Anna S , De Pedri Ewerton H , Fung Liang , Rossi Flavia , Duboc Gisele , Barone Antonio A , Costa Silvia F
Published: August 2007

Background

Considering the increasing use of polymyxins to treat infections due to multidrug resistant Gram-negative in many countries, it is important to evaluate different susceptibility testing methods to this class of antibiotic.

Methods

Susceptibility of 109 carbapenem-resistant P. aeruginosa to polymyxins was tested comparing broth microdilution (reference method), disc diffusion, and Etest using the new interpretative breakpoints of Clinical and Laboratory Standards Institute.

Results

Twenty-nine percent of isolates belonged to endemic clone and thus, these strains were excluded of analysis. Among 78 strains evaluated, only one isolate was resistant to polymyxin B by the reference method (MIC: 8.0 μg/mL). Very major and major error rates of 1.2% and 11.5% were detected comparing polymyxin B disc diffusion with the broth microdilution (reference method). Agreement within 1 twofold dilution between Etest and the broth microdilution were 33% for polymyxin B and 79.5% for colistin. One major error and 48.7% minor errors were found comparing polymyxin B Etest with broth microdilution and only 6.4% minor errors with colistin. The concordance between Etest and the broth microdilution (reference method) was respectively 100% for colistin and 90% for polymyxin B.

Conclusion

Resistance to polymyxins seems to be rare among hospital carbapenem-resistant P. aeruginosa isolates over a six-year period. Our results showed, using the new CLSI criteria, that the disc diffusion susceptibility does not report major errors (false-resistant results) for colistin. On the other hand, showed a high frequency of minor errors and 1 very major error for polymyxin B. Etest presented better results for colistin than polymyxin B. Until these results are reproduced with a large number of polymyxins-resistant P. aeruginosa isolates, susceptibility to polymyxins should be confirmed by a reference method.
Taurine chloramine differentially inhibits matrix metalloproteinase 1 and 13 synthesis in interleukin-1β stimulated fibroblast-like synoviocytes
Authors: Kim Kyoung Soo , Park Eun Kyung , Ju Seung Min , Jung Hye-Sook , Bang Jun Soo , Kim Chaekyun , Lee Yeon-Ah , Hong Seung-Jae , Lee Sang-Hoon , Yang Hyung-In , Yoo Myung Chul
Published: August 2007

It has been suggested that taurine chloramine (TauCl) plays an important role in the downregulation of proinflammatory mediators. However, little is known about its effect on the expression of matrix metalloproteinases (MMPs). In this study, we investigated the effects of TauCl on synovial expression of MMPs. The effects of TauCl on MMP expression in IL-1β stimulated fibroblast-like synoviocytes (FLSs) were studied using the following techniques. Real-time PCR and semi-quantitative PCR were employed to analyze the mRNA expression of MMPs. ELISA was used to determine protein levels of MMPs. Western blot analyses were performed to analyze the mitogen-activated protein kinase and inhibitor of nuclear factor-κB (IκB) kinase signalling pathways. Finally, electrophoretic mobility shift assay and immunohistochemistry were used to assess localization of transcription factors. IL-1β increased the transcriptional and translational levels of MMP-1 and MMP-13 in rheumatoid arthritis FLSs, whereas the levels of MMP-2 and MMP-9 were unaffected. TauCl at a concentration of 400 to 600 μmol/l greatly inhibited the transcriptional and translational expression of MMP-13, but the expression of MMP-1 was significantly inhibited at 800 μmol/l. At a concentration of 600 μmol/l, TauCl did not significantly inhibit phosphorylation of mitogen-activated protein kinase or IκB degradation in IL-1β stimulated rheumatoid arthritis FLSs. The degradation of IκB was significantly inhibited at a TauCl concentration of 800 μmol/l. The inhibitory effect of TauCl on IκB degradation was confirmed by electrophoretic mobility shift assay and immunochemical staining for localization of nuclear factor-κB. TauCl differentially inhibits the expression of MMP-1 and MMP-13, and inhibits expression of MMP-1 primarily through the inhibition of IκB degradation, whereas it inhibits expression of MMP-13 through signalling pathways other than the IκB pathway.
Prostaglandin E2 is a key factor for monocyte-derived dendritic cell maturation: enhanced T cell stimulatory capacity despite IDO
Authors: Krause Petra , Singer Eva , Darley Paula I , Klebensberger Janosch , Groettrup Marcus , Legler Daniel F
Published: August 2007

The exclusive ability of dendritic cells (DCs) to stimulate primary and secondary immune responses favors the use of antigen-loaded human monocyte-derived DCs (MoDCs) in vaccinations against tumors. Previous studies demonstrated that PGE2 is fundamental during MoDC maturation to facilitate migration toward lymph node-derived chemokines. A recent study challenged the use of PGE2, as PGE2 induced IDO in mature MoDCs. In MoDCs compatible for clinical use, we now demonstrate that PGE2 is responsible for IDO induction if matured by soluble CD40 ligand, LPS, or cytokines. In contrast, IDO expression in MoDCs matured by TLR3 triggering occurs independently of PGE2. It is surprising that despite active IDO protein, MoDCs matured with PGE2 display a greater potential to stimulate naïve CD4+ and CD8+ T cell proliferation, which is not increased further by IDO inhibition. Moreover, we found elevated levels of tryptophanyl-tRNA-synthetase (TTS) in T cells cultured with PGE2-matured MoDCs. Our data demonstrate that PGE2 induces IDO in MoDCs but that T cell-stimulating capacities of PGE2-matured MoDCs overcome IDO activity, probably through TTS induction. As PGE2 is critical for DC migration and enhances the capability of MoDCs to induce T cell proliferation, we highly recommend supplementing DC maturation stimuli with PGE2 for use in clinical trials.
Angiotensin II-Induced Mitogen-Activated Protein Kinase Phosphatase-1 Expression in Bovine Adrenal Glomerulosa Cells: Implications in Mineralocorticoid Biosynthesis
Authors: Casal Andrés J. , Ryser Stéphane , Capponi Alessandro M. , Wang-Buholzer Carine F.
Published: August 2007

Angiotensin II (AngII) stimulates aldosterone biosynthesis in the zona glomerulosa of the adrenal cortex. AngII also triggers the MAPK pathways (ERK1/2 and p38). Because ERK1/2 phosphorylation is a transient process, phosphatases could play a crucial role in the acute steroidogenic response. Here we show that the dual specificity (threonine/tyrosine) MAPK phosphatase-1 (MKP-1) is present in bovine adrenal glomerulosa cells in primary culture and that AngII markedly increases its expression in a time- and concentration-dependent manner (IC50 = 1 nm), a maximum of 548 ± 10% of controls being reached with 10 nm AngII after 3 h (n = 3, P < 0.01). This effect is completely abolished by losartan, a blocker of the AT1 receptor subtype. Moreover, this AngII-induced MKP-1 expression is reduced to 250 ± 35% of controls (n = 3, P < 0.01) in the presence of U0126, an inhibitor of ERK1/2 phosphorylation, suggesting an involvement of the ERK1/2 MAPK pathway in MKP-1 induction. Indeed, shortly after AngII-induced phosphorylation of ERK1/2 (220% of controls at 30 min), MKP-1 protein expression starts to increase. This increase is associated with a reduction in ERK1/2 phosphorylation, which returns to control values after 3 h of AngII challenge. Enhanced MKP-1 expression is essentially due to a stabilization of MKP-1 mRNA. AngII treatment leads to a 53-fold increase in phosphorylated MKP-1 levels and a doubling of MKP-1 phosphatase activity. Overexpression of MKP-1 results in decreased phosphorylation of ERK1/2 and aldosterone production in response to AngII stimulation. These results strongly suggest that MKP-1 is the specific phosphatase induced by AngII and involved in the negative feedback mechanism ensuring adequate ERK1/2-mediated aldosterone production in response to the hormone.
Contribution of Noradrenergic and Adrenergic Cell Groups of the Brainstem and Agouti-Related Protein-Synthesizing Neurons of the Arcuate Nucleus to Neuropeptide-Y Innervation of Corticotropin-Releasing Hormone Neurons in Hypothalamic Paraventricular Nucleus of the Rat
Authors: Füzesi Tamás , Wittmann Gábor , Liposits Zsolt , Lechan Ronald M. , Fekete Csaba
Published: August 2007

CRH-synthesizing neurons in the hypothalamic paraventricular nucleus (PVN) integrate neuronal and hormonal inputs and serve as a final common pathway to regulate the hypothalamic-pituitary-adrenal axis. One of the neuronal regulators of CRH neurons is neuropeptide Y (NPY) contained in axons that densely innervate CRH neurons. The three main sources of NPY innervation of the PVN are the hypothalamic arcuate nucleus and the noradrenergic and adrenergic neurons of the brainstem. To elucidate the origin of the NPY-immunoreactive (NPY-IR) innervation to hypophysiotropic CRH neurons, quadruple-labeling immunocytochemistry for CRH, NPY, dopamine-β-hydroxylase, and phenylethanolamine-N-methyltransferase was performed. Approximately 63% of NPY-IR varicosities on the surface of CRH neurons were catecholaminergic (22% noradrenergic and 41% adrenergic), and 37% of NPY-IR boutons were noncatecholaminergic. By triple-labeling immunofluorescence detection of NPY, CRH, and agouti-related protein, a marker of NPY axons projecting from the arcuate nucleus, the noncatecholaminergic, NPY-ergic axon population was shown to arise primarily from the arcuate nucleus. When NPY was administered chronically into the cerebral ventricle of fed animals, a dramatic reduction of CRH mRNA was observed in the PVN (NPY vs. control integrated density units, 23.9 ± 2.7 vs. 77.09 ± 15.9). We conclude that approximately two thirds of NPY-IR innervation to hypophysiotropic CRH neurons originates from catecholaminergic neurons of the brainstem, whereas the remaining one third arises from the arcuate nucleus. The catecholaminergic NPY innervation seems to modulate the activation of CRH neurons in association with glucoprivation and infection, whereas the NPY input from the arcuate nucleus may contribute to inhibition of CRH neurons during fasting.
The Dipeptidyl Peptidase 4 Inhibitor Vildagliptin Does Not Accentuate Glibenclamide-Induced Hypoglycemia but Reduces Glucose-Induced Glucagon-Like Peptide 1 and Gastric Inhibitory Polypeptide Secretion
Authors: El-Ouaghlidi Andrea , Rehring Erika , Holst Jens J. , Schweizer Anja , Foley James , Holmes David , Nauck Michael A.
Published: August 2007

Background/Aims: Inhibition of dipeptidyl peptidase 4 by vildagliptin enhances the concentrations of the active form of the incretin hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). The present study asked whether vildagliptin accentuates glibenclamide-induced hypoglycemia or affects endogenous secretion of GLP-1 and GIP after an oral glucose tolerance test.

Methods: There were 16 healthy male subjects studied on four occasions after an overnight fast in a double-blind, four-way crossover study. In random order, vildagliptin (100 mg) or placebo, with and without glibenclamide (5 mg), was administered 30 min before 75 g oral glucose. Blood was sampled to measure glucose, and total (sum of active and inactive) GLP-1 and GIP. Statistical evaluation was done using repeated-measures ANOVA.

Results: Glibenclamide provoked hypoglycemia (≤1.9 mm), but this was not accentuated by the simultaneous administration of vildagliptin (P = 0.25). The integrated incremental responses of total GLP-1 were reduced by vildagliptin by 72% (with glibenclamide) and 48% (without glibenclamide) (effect of vildagliptin: P < 0.0001; glibenclamide: P = 0.31; interaction: P = 0.26). Similarly, integrated incremental responses of total GIP were reduced by vildagliptin by 26 and 21%, with and without glibenclamide, respectively (vildagliptin: P = 0.017; glibenclamide: P = 0.44; interaction: P = 0.69).

Conclusions: Sulfonylurea-induced hypoglycemia after the oral administration of glibenclamide is not accentuated by the coadministration of vildagliptin. This may be explained by a negative feedback regulation of GLP-1 and GIP secretion that limits the degree to which the active incretin levels are enhanced.
Exercise Alone Reduces Insulin Resistance in Obese Children Independently of Changes in Body Composition
Authors: Bell Lana M. , Watts Katie , Siafarikas Aris , Thompson Alisha , Ratnam Nirubasini , Bulsara Max , Finn Judith , O’Driscoll Gerry , Green Daniel J. , Jones Timothy W. , Davis Elizabeth A.
Published: August 2007

Context: The number of obese children with insulin resistance and type 2 diabetes is increasing, but the best management strategy is not clear.

Objective: The objective of this study was to assess the effect of a structured 8-wk exercise training program on insulin resistance and changes in body composition in obese children.

Design: The study was 8 wk of structured supervised exercise intervention with outcome measures before and after the exercise period.

Subjects: Fourteen obese children (12.70 ± 2.32 yr; eight male, six female) with high fasting insulin levels were enrolled into the study.

Intervention: Intervention consisted of 8 wk of supervised circuit-based exercise training, composed of three fully supervised 1-h sessions per week.

Outcome Measures: Outcome measures were assessed pretraining program and posttraining program and included insulin sensitivity (euglycemic-hyperinsulinemic clamp studies), fasting insulin and glucose levels, body composition using dual energy x-ray absorptiometry scan, lipid profile, and liver function tests.

Results: Insulin sensitivity improved significantly after 8 wk of training (Mlbm 8.20 ± 3.44 to 10.03 ± 4.33 mg/kg·min, P < 0.05). Submaximal exercise heart rate responses were significantly lower following the training (P < 0.05), indicating an improvement in cardiorespiratory fitness. Dual energy x-ray absorptiometry scans revealed no differences in lean body mass or abdominal fat mass.

Conclusion: An 8-wk exercise training program increases insulin sensitivity in obese children, and this improvement occurred in the presence of increased cardiorespiratory fitness but is independent of measurable changes in body composition.
Neural plate morphogenesis during mouse neurulation is regulated by antagonism of Bmp signalling
Authors: Ybot-Gonzalez Patricia , Gaston-Massuet Carles , Girdler Gemma , Klingensmith John , Arkell Ruth , Greene Nicholas D. E. , Copp Andrew J.
Published: August 2007

Dorsolateral bending of the neural plate, an undifferentiated pseudostratified epithelium, is essential for neural tube closure in the mouse spinal region. If dorsolateral bending fails, spina bifida results. In the present study, we investigated the molecular signals that regulate the formation of dorsolateral hinge points (DLHPs). We show that Bmp2expression correlates with upper spinal neurulation (in which DLHPs are absent); that Bmp2-null embryos exhibit premature, exaggerated DLHPs;and that the local release of Bmp2 inhibits neural fold bending. Therefore,Bmp signalling is necessary and sufficient to inhibit DLHPs. By contrast, the Bmp antagonist noggin is expressed dorsally in neural folds containing DLHPs,noggin-null embryos show markedly reduced dorsolateral bending and local release of noggin stimulates bending. Hence, Bmp antagonism is both necessary and sufficient to induce dorsolateral bending. The local release of Shh suppresses dorsal noggin expression, explaining the absence of DLHPs at high spinal levels, where notochordal expression of Shh is strong. DLHPs`break through' at low spinal levels, where Shh expression is weaker. Zic2 mutant embryos fail to express Bmp antagonists dorsally and lack DLHPs, developing severe spina bifida. Our findings reveal a molecular mechanism based on antagonism of Bmp signalling that underlies the regulation of DLHP formation during mouse spinal neural tube closure.
Asthma: Anti-Immunoglobulin E Therapy with Omalizumab for Asthma
Authors: Hendeles Leslie , Sorkness Christine A
Published: August 2007

Objective:

To evaluate data on anti-immunoglobulin E (anti-IgE) therapy for asthma.

Data Sources:

Information was selected from PubMed from 1989 to May 2007 using the search term omalizumab and included randomized, controlled trials. These studies evaluated asthma treatment with omalizumab and focused on its efficacy, tolerability, and cost-effectiveness in this population.

Study Selection and Data Extraction:

All randomized clinical trials were reviewed (23 were identified and 19 were included; 3 were not relevant and 1 contained duplicative data). Other articles using the search words anti-IgE therapy and cost-effectiveness were evaluated; relevant information was extracted.

Data Synthesis:

IgE-dependent mechanisms play an important role in the development and maintenance of airway inflammation in asthma. Omalizumab is a subcutaneously administered monoclonal anti-IgE antibody that reduces unbound IgE concentrations and promotes down-regulation of IgE receptors. Results from clinical trials in adults, adolescents, and children with poorly controlled IgE-mediated asthma have shown that omalizumab improves symptom control and allows patients to be managed with lower doses of inhaled corticosteroids (ICS). It has been well tolerated in clinical trials lasting as long as 52 weeks, but injection-site reactions are common (45% in omalizumab group vs 43% in placebo group) and anaphylaxis has occurred in 0.2% of patients. A consensus expert panel has recommended that omalizumab should be considered for patients 12 years of age or older with allergic asthma who are inadequately controlled on guideline-based therapy and require maintenance therapy with systemic corticosteroids or high-dose ICSs, or who have poor adherence to ICS therapy.

Conclusions:

Anti-IgE therapy provides an effective and generally safe approach to the treatment of patients with IgE-mediated asthma who are not adequately controlled by conventional guideline-based medications. However, the potential benefit must be weighed against the cost and inconvenience of this new therapy.
The Brain Cytoplasmic RNA BC1 Regulates Dopamine D2Receptor-Mediated Transmission in the Striatum
Authors: Centonze Diego , Rossi Silvia , Napoli Ilaria , Mercaldo Valentina , Lacoux Caroline , Ferrari Francesca , Ciotti Maria Teresa , De Chiara Valentina , Prosperetti Chiara , Maccarrone Mauro , Fezza Filomena , Calabresi Paolo , Bernardi Giorgio , Bagni Claudia
Published: August 2007

Dopamine D2receptor (D2DR)-mediated transmission in the striatum is remarkably flexible, and changes in its efficacy have been heavily implicated in a variety of physiological and pathological conditions. Although receptor-associated proteins are clearly involved in specific forms of synaptic plasticity, the molecular mechanisms regulating the sensitivity of D2receptors in this brain area are essentially obscure. We have studied the physiological responses of the D2DR stimulations in mice lacking the brain cytoplasmic RNA BC1, a small noncoding dendritically localized RNA that is supposed to play a role in mRNA translation. We show that the efficiency of D2-mediated transmission regulating striatal GABA synapses is under the control of BC1 RNA, through a negative influence on D2receptor protein level affecting the functional pool of receptors. Ablation of the BC1 gene did not result in widespread dysregulation of synaptic transmission, because the sensitivity of cannabinoid CB1receptors was intact in the striatum of BC1 knock-out (KO) mice despite D2and CB1receptors mediated similar electrophysiological actions. Interestingly, the fragile X mental retardation protein FMRP, one of the multiple BC1 partners, is not involved in the BC1 effects on the D2-mediated transmission. Because D2DR mRNA is apparently equally translated in the BC1-KO and wild-type mice, whereas the protein level is higher in BC1-KO mice, we suggest that BC1 RNA controls D2DR indirectly, probably regulating translation of molecules involved in D2DR turnover and/or stability.