bluuebunny/crossref_metadata_2025 huggingface dataset:
Party Groups and Policy Positions in the European Parliament
Authors: McElroy Gail , Benoit Kenneth
Published: December 2006

As the legislative body of the European Union (EU), the European Parliament (EP) comprises 732 elected representatives from over 150 national political parties from 25 member states. At the EP level, these members are affiliated with seven major party groups representing distinct policy positions. Here we provide precise estimates of these policy positions based on expert surveys, in addition to characterizing the dimensionality of policy competition in the EP. Our results suggest not only that party groups have identifiable and differentiated positions on multiple issues of policy, but also that these positions group broadly into two orthogonal dimensions: one consisting of classic left-right social and economic issues, and the other related to the powers and scope of EU institutions.
Charisma, Leader Effects and Support for Right-Wing Populist Parties
Authors: van der Brug Wouter , Mughan Anthony
Published: December 2006

One of the ways in which support for right-wing populist parties is held to be distinctive from that for other kinds of political parties is that their leaders are alleged to be ‘charismatic’ figures who play a crucial role in the electoral success their parties have enjoyed. Focusing on three Dutch elections, this article tests the charismatic leadership hypothesis, asking whether leader effects are stronger for populist than for established parties and whether they are stronger for populist leaders who are widely held to be more rather than less charismatic. The results indicate that if, following Weber, charisma is seen as an intimate and direct bond between leaders and followers, there is in fact little support for the charismatic leadership hypothesis, at least in the context of leaders shaping electoral outcomes. While recognizing that charisma may manifest itself in other, perhaps indirect, ways, there would seem to us at the very least to be a need for the notion of charisma to be conceptualized more rigorously if it is to continue to be used as an explanation of right-wing populist party success.
The New Sub-National Politics of the British Labour Party
Authors: Laffin Martin , Shaw Eric , Taylor Gerald
Published: December 2006

The response of national, state-level political parties to the challenges of competing for power at the devolved, regional levels is a neglected research topic. This article seeks to remedy this by analysing how the British Labour Party has responded to these challenges at the sub-national level following UK devolution. British Labour remains formally a unitary party despite devolution. Nonetheless, the national party leadership has allowed the Scottish and Welsh Labour Parties considerable freedom, in practice, to select candidates, conduct regional-level elections and implement some distinctive policies. Meanwhile, the Scottish and Welsh Labour Parties have shifted significantly from being traditional, centralized parties with a single hierarchical organization towards being more pluralist, less hierarchical organizations.
The Front-Runner Falls
Authors: McSweeney Dean
Published: December 2006

From 1980 until 2000, two indicators successfully predicted presidential nominees in advance of the contest: the front-runner in the latest poll of party identifiers and the leader in fundraising in the previous year. In 2004, both indicators predicted Howard Dean to win the Democratic nomination and both were incorrect. In accounting for the failure of these predictions, this article shows that Dean was an untypically weak front-runner compared to his predecessors. His relative weaknesses included a lower level of support, a narrower lead and less name recognition. In competing against his opponents, Dean was vulnerable to the importance primary voters attached to ability to win the election and their lateness in deciding for whom to vote. These features of the contest disadvantaged Dean and enabled John Kerry to ride a bandwagon to a quick victory.
Collaborative Action Research within Developmental Evaluation
Authors: Cook Tina
Published: December 2006

This article investigates the use of collaborative action research in both the development and evaluation of a project designed to develop inclusive practice in Early Years and childcare settings.The purpose of the evaluation was to ascertain how practitioners understand the term ‘inclusion’, how those understandings were translated into practice and how changes in that practice might be conceptualized and carried out.The article explores the use of facilitated collaborative action research as a core element in developmental evaluation. Reflecting on other approaches such as theory of change, it considers whether the use of action research supported the critical examination and development of a project, or whether, by being so similar in design, it constricted the evaluation in terms of reliability of data, accountability and providing a framework for planning and development.
The European Structural Funds and Sustainable Development
Authors: Ekins Paul , Medhurst James
Published: December 2006

Sustainable development (SD) is now a broad policy objective in the European Union (EU). This article explores how the contribution to SD of the EU Structural Funds (SFs) might be evaluated. It suggests the use of a ‘four-capitals model’ of SD, and outlines how commonly accepted principles and dimensions of sustainability might be interpreted within such a model. The article then reviews various approaches to SD indicators, concluding that an indicator framework is preferable to the various methods of aggregation of indicators that have been proposed. It then relates the indicator issue to the framework for evaluation of the SFs set out by the European Commission. Out of this discussion an illustrative indicator set for such an evaluation, related to the four-capitals model of SD, is derived.
Presenting figurative idioms with a touch of etymology: more than mere mnemonics?
Authors: Boers Frank , Eyckmans June , Stengers Hélène
Published: December 2006

Instead of being completely arbitrary, the meaning of many idioms is ‘motivated’ by their original, literal usage. In an FLT context, this offers the possibility of presenting idioms in ways that promote insightful learning rather than ‘blind’ memorization. Associating an idiom with its etymology has been shown to enhance retention. This effect seems in accordance with Dual Coding theory, as the etymological association is likely to call up a mental image of a concrete scene which can be stored in memory alongside the verbal form. The present study explores the possibility of taking this technique beyond ‘mere’ mnemonics. We report a series of experiments that were set up with the participation of students of English in higher education. The results show that knowledge of the origin of idioms can effectively help learners comprehend their figurative meaning. Not only does the problem-solving task of inferring idiomatic meaning on the basis of etymological information appear feasible, it seems to facilitate recall, too, as predicted by Levels-of-processing theory in general. Finally, the results suggest that knowledge of the origin of certain idioms can help learners estimate whether they might be typical of informal discourse.
Tensions in a non-traditional Spanish classroom
Authors: Bloom Melanie
Published: December 2006

Through a teacher-research project, I examined the tensions that emerged while negotiating with the students the curriculum for a Spanish for healthcare professionals course. I explore the tensions related to four emergent themes: student-centred versus teacher-centred learning, self-efficacy versus laissez faire work ethic, communication versus accuracy, and process versus product orientation. These themes are exemplified and analysed through the presentation of narratives based on the data collected. I present insights gained from this research and suggestions for teachers interested in engaging in curricular negotiation and/or innovation.
Local Culture, Globalization and Policy Outcomes
Authors: Wilson Gail
Published: December 2006

It is argued that the impact of globalization and global ideologies on social policy can depend on the ways that local cultures reinforce or combat global ideologies and pressures. The article discusses the importance of local policy factors in shaping responses to globalization, taking as an example the way in which global forces have affected outcomes for older people needing long-term care in one marginalized province of a rich country. Local political, economic and sociocultural factors can reinforce global pressures for neo-liberal policies and rising individualism and overwhelm the global ideologies of democracy and human rights (including gender rights and anti ageism) that might lead to better outcomes for older people and their caregivers. In the New Brunswick province of Canada, traditional cultural values can be seen as one factor allowing politicians to make suboptimal social policy choices.
Consuming national themed environments abroad
Authors: West Brad
Published: December 2006

This article examines Australian working holidaymaker patronage of ‘Aussie’ theme pubs in London to explore meanings of the national themed environment. From semi-structured interviews and ethnographic fieldwork at three venues, it is argued that themed space can be interacted with in highly reflective ways while working to facilitate the reimagining of national identity. This finding challenges post-modern, critical and Weberian perspectives that argue the ersatz nature of themed space overwhelms actors’ ability to think critically while severing traditional connections with historical time. Attention is drawn to the polysemic dimensions of themed representations and the new ways that actors can engage with the nation in a globalizing world.
Teacher expectations of student reading in middle and high schools
Authors: Tao Liqing , Yuan Haiwang , Zuo Li , Qian Gaoyin , Murray Bruce
Published: December 2006

English

This article investigates China’s middle school and secondary school teacher expectations of student book use as an aspect of learning environments. A questionnaire was used to probe the following teacher expectations: physical accessibility of books, homework, mastery of texts and types of extra-curricular reading materials. Results showed China’s teachers believed in mastering exemplary texts and the moral value of reading materials. Homework was viewed as a means to enhance student learning. The findings of the article can help educators understand better the learning environments of Chinese students and can offer a critical comparison of learning environments across cultures.

French

Cette étude analyse ce que les enseignants des établissements d'enseignement secondaire (inférieur et supérieur) en Chine attendent des élèves en matière d'utilisation de livres comme aspect des environnements d'apprentissage. Un questionnaire a ainsi été utilisé pour mieux connaître les attentes des enseignants en termes d'accessibilité physique des ouvrages, de travail à la maison, de connaissance approfondie des textes et de types de documents lus en dehors du programme. Les résultats ont montré que les enseignants des établissements concernés par cette étude accordent de l'importance à la connaissance approfondie des textes de référence et à la valeur morale des documents de lecture. Le travail à la maison est quant à lui considéré comme un moyen permettant d'améliorer l'apprentissage des élèves. Les résultats de cette étude peuvent aider les professionnels de l'éducation à mieux comprendre les environnements d'apprentissage des élèves chinois et apporter un élément de comparaison pour étudier les environnements d'apprentissage de différentes cultures.

Spanish

En este estudio se investigan las expectativas de los profesores de colegios de secundaria en China con respecto al uso de los libros por parte de los alumnos como un aspecto del entorno de aprendizaje. Se utilizó un cuestionario para indagar sobre las siguientes expectativas de los docentes: accesibilidad física de los libros, tareas para la casa, conocimiento profundo de los textos y tipos de materiales de lectura extracurriculares. Los resultados mostraron que los profesores de los colegios estudiados valoran el conocimiento profundo de textos ejemplares y el contenido moral de los materiales de lectura. Las tareas para realizar en casa se ven como un medio de mejorar el aprendizaje de los alumnos. Las conclusiones de este estudio pueden ayudar a los educadores a comprender mejor los entornos de aprendizaje de los alumnos de China y ofrecer un punto de referencia crítico para comparar entornos similares en otras culturas.
Towards an understanding of holistic education in the middle years of education
Authors: Hare John
Published: December 2006

English

Holistic education lacks a single definition but may be described through a number of recurrent themes that appear in the literature. These themes have been used to develop underlying values that reflect this educational approach and the behaviours associated with these values are described. A person profile is presented from these values and behaviours and describes the attributes, abilities and competencies of a student who has benefited from holistic education in the middle years of their education. The advantages of the person profile are discussed.

French

Il n'existe pas de définition unique de l'éducation globale; celle-ci peut cependant être décrite grÀce à un certain nombre de thèmes qui apparaissent de façon récurrente dans la littérature. L'auteur utilise ces thèmes pour développer les valeurs sous-jacentes qui caractérisent cette approche éducative et décrire les comportements associés à ces valeurs. Il établit le profil d'une personne à partir de ces valeurs et comportements, profil qui décrit les qualités, les aptitudes et les compétences d'un élève ayant bénéficié d'une éducation globale au cours du premier cycle du secondaire. Enfin, il analyse les avantages du profil de cette personne.

Spanish

No existe una definición única para `educación holística'; no obstante, ésta se puede describir por medio de una serie de elementos recurrentes en la literatura especializada. El autor se basa en tales elementos para desarrollar los valores subyacentes a la educación holística y describe las conductas asociadas a dichos valores. Presenta también un perfil personal basado en estos valores y conductas, y describe los atributos, habilidades y competencias esperados en los alumnos que hayan participado de una educación holística durante los años de enseñanza media. Asimismo, analiza las ventajas del perfil personal.
Critical evaluation of appreciative inquiry
Authors: Grant Suzanne , Humphries Maria
Published: December 2006

Despite increased applications and scholarship, appreciative inquiry remains a research method with little self-reflection or critique to evaluate the process as an action research method. Perhaps counter-intuitively, we propose that critical theory provides one useful lens through which to develop an appreciative evaluation of the process. We begin this article with a brief introduction to appreciative inquiry (Ai) as it is presented in the literature. Calls for evaluation of the process are acknowledged, as are the few evaluations/critiques of Ai we have found in literature. We discuss how critical theory may be applied to an evaluation of appreciative inquiry bridging an apparent paradox between the negativity associated with the former and the positive focus of the latter. An initial application of Critical Appreciative Process (CAP) is described to illustrate how the integrated use of appreciative inquiry and critical theory deepens insight and recognition of the complexity in human endeavours.
Comparison of functions for evaluating the effect of Fe and Al oxides on the particle size distribution of kaolin and quartz
Authors: Arias M. , Lopez E. , Barral M. T.
Published: December 2006

Although it is generally agreed that Fe and Al can act to bind soil particles, their relative efficiencies as aggregants are still disputed. In this work, the aggregating efficiencies of both aged and non-aged Fe and Al oxides precipitated on kaolin or quartz substrates were characterized by comparing their effects on particle size distributions (PSD). To facilitate comparison of PSD data, these were parameterized by fitting them with five different probability density functions (the normal, lognormal, Jaky, fractal and Rosin-Rammler functions). The best fits were given by the Rosin-Rammler function (R2 = 0.997), whose α parameter was used to compare the aggregating efficiency of Fe and Al oxides: in order of decreasing efficiency, non-aged Al > non-aged Fe ≈ aged Fe > aged Al-precipitates.
Solid-state 27Al and 29Si NMR analysis of hydroxy-Cr and-Al interlayered montmorillonite
Authors: Dubbin W. E. , Goh Tee Boon
Published: December 2006

The ease with which sorbed Cr(III) is released to solution via oxidation or cation exchange depends on its mode of complexation and the broader chemical environment in which it is held. This study was conducted to elucidate the chemical environment of hydrolysed Cr(III) sorbed onto montmorillonite, both alone and coprecipitated with Al. The 27Al MAS NMR revealed that Cr in the coprecipitated hydroxy interlayer created a second environment for AI, slightly more shielded than that of Al in the montmorillonite 2:1 layer. This observation is evidence for the presence of numerous Al-O-Cr linkages, thus revealing a uniform distribution of Al and Cr within the hydroxy polymers. The 29Si MAS NMR revealed a second environment for Si in the tetrahedral sheet of the Cr clays. This environment could be created only through a redistribution of electrons at the siloxane surface caused by inner-sphere complexation of Cr(III). Due to this inner-sphere complexation, sorbed Cr(III) is difficult to displace via simple exchange reactions and, consequently, its bioavailability is decreased.
Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions
Authors: Undas Anetta , Brummel-Ziedins Kathleen E. , Mann Kenneth G.
Published: December 2006

Aspirin is effective in the prevention of cardiovascular events in high-risk patients. The primary established effect of aspirin on hemostasis is to impair platelet aggregation via inhibition of platelet thromboxane A2 synthesis, thus reducing thrombus formation on the surface of the damaged arterial wall. Growing evidence also indicates that aspirin exerts additional antithrombotic effects, which appear to some extent unrelated to platelet thromboxane A2 production. Aspirin can reduce thrombin generation with the subsequent attenuation of thrombin-mediated coagulant reactions such as factor XIII activation. Aspirin also acetylates lysine residues in fibrinogen resulting in increased fibrin clot permeability and enhanced clot lysis as well as directly promoting fibrinolysis with high-dose aspirin. The variable effectiveness of aspirin in terms of clinical outcomes and laboratory findings, which has been termed aspirin resistance, may be related to these additional antithrombotic effects that are altered when associated with common genetic polymorphisms such as the Leu33Pro β3-integrin or Val34Leu factor XIII mutations. However, the clinical relevance of these observations is still unclear. Elucidation of the actual impacts of aspirin other than antiaggregation effects could be important in view of the widespread use of this drug in the prevention of thrombotic manifestations of atherosclerosis.
Inability of memory T cells to induce graft-versus-host disease is a result of an abortive alloresponse
Authors: Chen Benny J. , Deoliveira Divino , Cui Xiuyu , Le Ngocdiep T. , Son Jessica , Whitesides John F. , Chao Nelson J.
Published: December 2006

Several groups, including our own, have independently demonstrated that effector memory T cells from non–alloantigen-primed donors do not cause graft-versus-host disease (GVHD). In the current study, we further investigated whether this approach could be extended to all memory T cells, and we studied the underlying mechanisms. Neither total memory T cells nor purified central memory T cells were able to induce GVHD. Memory T cells were at least 3-log less potent than bulk T cells in mediating GVHD. As expected, memory T cells failed to elicit cytotoxicity and proliferated poorly against alloantigens in standard 5-day mixed-lymphocyte cultures. However, the proliferative responses of memory T cells were more comparable with those of bulk and naive T cells when the culture time was shortened. Moreover, the frequencies of IL-2–secreting cells measured by 42-hour enzyme-linked immunosorbent spot (ELISPOT) assay were similar among naive, memory, and bulk T cells. These data indicated that memory T cells are able to respond to alloantigens initially but fail to develop to full potential. The abortive immune response, which was mediated by non–alloantigen-specific memory T cells in response to alloantigens, may explain why memory T cells from unprimed and non–alloantigen-primed donors could not induce GVHD.
Congenital erythropoietic porphyria due to a mutation in GATA1: the first trans-acting mutation causative for a human porphyria
Authors: Phillips John D. , Steensma David P. , Pulsipher Michael A. , Spangrude Gerald J. , Kushner James P.
Published: December 2006

Congenital erythropoietic porphyria (CEP), an autosomal recessive disorder, is due to mutations of uroporphyrinogen III synthase (UROS). Deficiency of UROS results in excess uroporphyrin I, which causes photosensitization. We evaluated a 3-year-old boy with CEP. A hypochromic, microcytic anemia was present from birth, and platelet counts averaged 70 × 109/L (70 000/μL). Erythrocyte UROS activity was 21% of controls. Red cell morphology and globin chain labeling studies were compatible with β-thalassemia. Hb electrophoresis revealed 36.3% A, 2.4% A2, 59.5% F, and 1.8% of an unidentified peak. No UROS or α- and β-globin mutations were found in the child or the parents. The molecular basis of the phenotype proved to be a mutation of GATA1, an X-linked transcription factor common to globin genes and heme biosynthetic enzymes in erythrocytes. A mutation at codon 216 in the child and on one allele of his mother changed arginine to tryptophan (R216W). This is the first report of a human porphyria due to a mutation in a trans-acting factor and the first association of CEP with thalassemia and thrombocytopenia. The Hb F level of 59.5% suggests a role for GATA-1 in globin switching. A bone marrow allograft corrected both the porphyria and the thalassemia.
Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and P-selectin in mediating accelerated platelet clearance
Authors: Othman Maha , Labelle Andrea , Mazzetti Ian , Elbatarny Hisham S. , Lillicrap David
Published: December 2006

Thrombocytopenia has been consistently reported following the administration of adenoviral gene transfer vectors. The mechanism underlying this phenomenon is currently unknown. In this study, we have assessed the influence of von Willebrand Factor (VWF) and P-selectin on the clearance of platelets following adenovirus administration. In mice, thrombocytopenia occurs between 5 and 24 hours after adenovirus delivery. The virus activates platelets and induces platelet-leukocyte aggregate formation. There is an associated increase in platelet and leukocyte-derived microparticles. Adenovirus-induced endothelial cell activation was shown by VCAM-1 expression on virus-treated, cultured endothelial cells and by the release of ultra-large molecular weight multimers of VWF within 1 to 2 hours of virus administration with an accompanying elevation of endothelial microparticles. In contrast, VWF knockout (KO) mice did not show significant thrombocytopenia after adenovirus administration. We have also shown that adenovirus interferes with adhesion of platelets to a fibronectin-coated surface and flow cytometry revealed the presence of the Coxsackie adenovirus receptor on the platelet surface. We conclude that VWF and P-selectin are critically involved in a complex platelet-leukocyte-endothelial interplay, resulting in platelet activation and accelerated platelet clearance following adenovirus administration.
In the absence of IGF-1 signaling, IFN-γ suppresses human malignant T-cell growth
Authors: Conti Laura , Regis Gabriella , Longo Angela , Bernabei Paola , Chiarle Roberto , Giovarelli Mirella , Novelli Francesco
Published: December 2006

Several approaches to target insulin-like growth factor-1 (IGF-1) signaling have resulted in the inhibition of the growth of a broad range of tumor cells. Malignant T cells are insensitive to the antiproliferative effects of the interferon-γ (IFN-γ)/signal transducer and activator of transcription 1 (STAT1) pathway because of the IGF-1–dependent internalization of the IFN-γR2 signaling chain. Here we show that human malignant T cells are also resistant to the growth inhibitory effect of both the IGF-1 receptor–specific inhibitor picropodophyllin (PPP) and retrovirus-mediated gene transfer of a dominant negative IGF-1 receptor. However, blockade of IGF-1 receptor perturbs IFN-γR2 internalization and induces its cell surface accumulation in malignant T cells. This allows the reinstatement of the IFN-γ–induced STAT1 activation, a high expression of proapoptotic molecules, and the suppression of malignant T-cell growth both in vitro and in vivo in a severe combined immunodeficiency (SCID) mouse model. These data indicate that the inhibition of IGF-1 signaling combined with IFN-γ administration could be a promising approach to suppress the growth of neoplastic T cells resistant to each treatment on its own.
Comprehensive analysis of homeobox genes in Hodgkin lymphoma cell lines identifies dysregulated expression of HOXB9 mediated via ERK5 signaling and BMI1
Authors: Nagel Stefan , Burek Christof , Venturini Letizia , Scherr Michaela , Quentmeier Hilmar , Meyer Corinna , Rosenwald Andreas , Drexler Hans G. , MacLeod Roderick A. F.
Published: December 2006

Many members of the nearly 200-strong homeobox gene family have been implicated in cancer, mostly following ectopic expression. In this study we analyzed homeobox gene expression in Hodgkin lymphoma (HL) cell lines. Both reverse transcription–polymerase chain reaction (RT-PCR) using degenerate primers and microarray profiling identified consistently up-regulated HOXB9 expression. Analysis of HOXB9 regulation in HL cells revealed E2F3A and BMI1 as activator and repressor, respectively. Furthermore, a constitutively active ERK5 pathway was identified in all HL cell lines analyzed as well as primary HL cells. Our data show that ERK5 probably mediates HOXB9 expression by repressing BMI1. In addition, expression analysis of the neighboring microRNA gene mir-196a1 revealed coregulation with HOXB9. Functional analysis of HOXB9 by knockdown and overexpression assays indicated their influence on both proliferation and apoptosis in HL cells. In summary, we identified up-regulation of HOXB9 in HL mediated by constitutively active ERK5 signaling which may represent novel therapeutic targets in HL.
Development of the hemangioblast defines the onset of hematopoiesis in human ES cell differentiation cultures
Authors: Kennedy Marion , D'Souza Sunita L. , Lynch-Kattman Macarena , Schwantz Staci , Keller Gordon
Published: December 2006

The onset of hematopoiesis in the mouse embryo and in the embryonic stem (ES) cell differentiation model is defined by the emergence of the hemangioblast, a progenitor with both hematopoietic and vascular potential. While there is evidence for the existence of a hemangioblast in the mouse, it is unclear if this progenitor develops during the establishment of the human hematopoietic system. In this report, we have mapped hematopoietic development in human ES cell (hESC) differentiation cultures and demonstrated that a comparable hemangioblast population exists. The human hemangioblasts were identified by their capacity to generate blast colonies that display both hematopoietic and vascular potential. These colony-forming cells express the receptor tyrosine kinase KDR (VEGF receptor 2) and represent a transient population that develops in BMP-4–stimulated embryoid bodies (EBs) between 72 and 96 hours of differentiation, prior to the onset of the primitive erythroid program. Two distinct types of hemangioblasts were identified, those that give rise to primitive erythroid cells, macrophages, and endothelial cells and those that generate only the primitive erythroid population and endothelial cells. These findings demonstrate for the first time the existence of the human hemangioblast and in doing so identify the earliest stage of hematopoietic commitment.
Topology testing of phylogenies using least squares methods
Authors: Czarna Aleksandra , Sanjuán Rafael , González-Candelas Fernando , Wróbel Borys
Published: December 2006

Background

The least squares (LS) method for constructing confidence sets of trees is closely related to LS tree building methods, in which the goodness of fit of the distances measured on the tree (patristic distances) to the observed distances between taxa is the criterion used for selecting the best topology. The generalized LS (GLS) method for topology testing is often frustrated by the computational difficulties in calculating the covariance matrix and its inverse, which in practice requires approximations. The weighted LS (WLS) allows for a more efficient albeit approximate calculation of the test statistic by ignoring the covariances between the distances.

Results

The goal of this paper is to assess the applicability of the LS approach for constructing confidence sets of trees. We show that the approximations inherent to the WLS method did not affect negatively the accuracy and reliability of the test both in the analysis of biological sequences and DNA-DNA hybridization data (for which character-based testing methods cannot be used). On the other hand, we report several problems for the GLS method, at least for the available implementation. For many data sets of biological sequences, the GLS statistic could not be calculated. For some data sets for which it could, the GLS method included all the possible trees in the confidence set despite a strong phylogenetic signal in the data. Finally, contrary to WLS, for simulated sequences GLS showed undercoverage (frequent non-inclusion of the true tree in the confidence set).

Conclusion

The WLS method provides a computationally efficient approximation to the GLS useful especially in exploratory analyses of confidence sets of trees, when assessing the phylogenetic signal in the data, and when other methods are not available.
Gene transfer and expression in human neutrophils. The phox homology domain of p47
phox
translocates to the plasma membrane but not to the membrane of mature phagosomes
Authors: Johnson Jennifer L , Ellis Beverly A , Munafo Daniela B , Brzezinska Agnieszka A , Catz Sergio D
Published: December 2006

Background

Neutrophils are non-dividing cells with poor survival after isolation. Consequently, exogenous gene expression in neutrophils is challenging. We report here the transfection of genes and expression of active proteins in human primary peripheral neutrophils using nucleofection.

Results

Exogenous gene expression in human neutrophils was achieved 2 h post-transfection. We show that neutrophils transfected by nucleofection are functional cells, able to respond to soluble and particulate stimuli. They conserved the ability to undergo physiological processes including phagocytosis. Using this technique, we were able to show that the phox homology (PX) domain of p47
phox
localizes to the plasma membrane in human neutrophils. We also show that RhoB, but not the PX domain of p47
phox
, is translocated to the membrane of mature phagosomes.

Conclusion

We demonstrated that cDNA transfer and expression of exogenous protein in human neutrophils is compatible with cell viability and is no longer a limitation for the study of protein function in human neutrophils.
Erratum to: Identification of specific calcitonin-like receptor residues important for calcitonin gene-related peptide high affinity binding
Authors: Banerjee Sugato , Evanson Janel , Harris Erik , Lowe Stephen L , Speth Robert C , Thomasson Kathryn A , Porter James E
Published: December 2006

This is a correction article.

After publication of this work [1], we became aware of the fact that Robert C. Speth was not included as an author. Dr. Speth put a considerable amount of time and effort into developing and preparing the radiopeptide used to carry out the radioligand binding studies reported in this manuscript and therefore should have originally been included as an author. We apologize to Dr. Speth for any inconvenience that this oversight might have caused and thank him for his invaluable contribution to this project.
Gefitinib (IRESSA) sensitive lung cancer cell lines show phosphorylation of Akt without ligand stimulation
Authors: Noro Rintaro , Gemma Akihiko , Kosaihira Seiji , Kokubo Yutaka , Chen Mingwei , Seike Masahiro , Kataoka Kiyoko , Matsuda Kuniko , Okano Tetsuya , Minegishi Yuji , Yoshimura Akinobu , Kudoh Shoji
Published: December 2006

Background

Phase III trials evaluating the efficacy of gefitinib (IRESSA) in non-small cell lung cancer (NSCLC) lend support to the need for improved patient selection in terms of gefitinib use. Mutation of the epidermal growth factor receptor (EGFR) gene is reported to be associated with clinical responsiveness to gefitinib. However, gefitinib-sensitive and prolonged stable-disease-defined tumors withoutEGFRgene mutation have also been reported.

Methods

To identify other key factors involved in gefitinib sensitivity, we analyzed the protein expression of molecules within the EGFR family, PI3K-Akt and Ras/MEK/Erk pathways and examined the sensitivity to gefitinib using the MTT cell proliferation assay in 23 lung cancer cell lines.

Results

We identified one highly sensitive cell line (PC9), eight cell lines displaying intermediate-sensitivity, and 14 resistant cell lines. Only PC9 and PC14 (intermediate-sensitivity) displayed anEGFRgene mutation including amplification. Eight out of the nine cell lines showing sensitivity had Akt phosphorylation without ligand stimulation, while only three out of the 14 resistant lines displayed this characteristic (P= 0.0059). Furthermore, the ratio of phosphor-Akt/total Akt in sensitive cells was higher than that observed in resistant cells (P= 0.0016). Akt phosphorylation was partially inhibited by gefitinib in all sensitive cell lines.

Conclusion

These results suggest that Akt phosphorylation without ligand stimulation may play a key signaling role in gefitinib sensitivity, especially intermediate-sensitivity. In addition, expression analyses of the EGFR family,EGFRgene mutation, and FISH (fluorescencein situhybridization) analyses showed that the phosphorylated state of EGFR and Akt might be a useful clinical marker of Akt activation without ligand stimulation, in addition toEGFRgene mutation and amplification, particularly in adenocarcinomas.
Malignant colo-duodenal fistula; case report and review of the literature
Authors: Soulsby Ruth , Leung Edmund , Williams Nigel
Published: December 2006

Background

Colo-duodenal fistula is a rare complication of malignant and inflammatory bowel disease. Cases with malignant colo-duodenal fistulae can present with symptoms from the primary, from the fistula or from metastatic disease. The fistula often results in diarrhoea and vomiting with dramatic weight loss. Upper abdominal pain is usually present as is general malaise both from the presence of the disease and from the metabolic sequelae it causes. The diarrhoea relates to colonic bacterial contamination of the upper intestines rather than to a pure mechanical effect. Vomiting may be faeculant or truly faecal and eructation foul smelling but in the case reports this 'classic' symptomatology was often absent despite a fistula being present and patent enough to allow barium through it. Occasionally patients will present with a gastro-intestinal bleed.

Case presentation

We present an unusual case of colorectal carcinoma, where a 65 year old male patient presented with diarrhoea and vomiting secondary to a malignant colo-duodenal fistula near the hepatic flexure. Adenocarcinoma was confirmed on histology from a biopsy obtained during the patient's oesophageogastroduodenoscopy, and the fistula was demonstrated in his barium enema. Staging computed tomography showed a locally advanced carcinoma of the proximal transverse colon, with a fistula to the duodenum and regional lymphadenopathy. The patient was also found to have subcutaneous metastasis. Following discussions at the multidisciplinary meeting, this patient was referred for palliation, and died within 4 months after discharge from hospital.

Conclusion

We present the case, discuss the management and review the literature. Colo-duodenal fistulae from colonic primaries are rare but early diagnosis may allow curative surgery. This case emphasises the importance of accurate staging and repeated clinical examination.
Influenza A virus infection engenders a poor antibody response against the ectodomain of matrix protein 2
Authors: Feng JingQi , Zhang Manxin , Mozdzanowska Krystyna , Zharikova Darya , Hoff Henry , Wunner William , Couch Robert B , Gerhard Walter
Published: December 2006

Background

Matrix protein 2 (M2) is an integral tetrameric membrane protein of influenza A virus (IAV). Its ectodomain (M2e) shows remarkably little diversity amongst human IAV strains. As M2e-specific antibodies (Abs) have been shown to reduce the severity of infection in animals, M2e is being studied for its capability of providing protection against a broad range of IAV strains. Presently, there is little information about the concentration of M2e-specific Abs in humans. Two previous studies made use of ELISA and Western blot against M2e peptides and recombinant M2 protein as immunosorbents, respectively, and reported Ab titers to be low or undetectable. An important caveat is that these assays may not have detected all Abs capable of binding to native tetrameric M2e. Therefore, we developed an assay likely to detect all M2e tetramer-specific Abs.

Results

We generated a HeLa cell line that expressed full length tetrameric M2 (HeLa-M2) or empty vector (HeLa-C10) under the control of the tetracycline response element. These cell lines were then used in parallel as immunosorbents in ELISA. The assay was standardized and M2e-specific Ab titers quantified by means of purified murine or chimeric (mouse variable regions, human constant regions) M2e-specific Abs in the analysis of mouse and human sera, respectively. We found that the cell-based ELISA was substantially more effective than immobilized M2e peptide in detecting M2e-specific Abs in sera of mice that had recovered from repetitive IAV infections. Still, titers remained low (< 5 μg/ml) even after two consecutive infections but increased to ~50 μg/ml after the third infection. Competition with free M2e peptide indicated that ~20% of M2e-specific Abs engendered by infection reacted with M2e peptide. In humans presenting with naturally acquired influenza virus infection, 11 of 24 paired sera showed a ≥ 4-fold increase in M2e-specific Ab titer. The Ab response appeared to be of short duration as titers were very low (average 0.2 μg/ml) in all patients at onset of infection and in controls, in spite of evidence for previous exposure to IAV.

Conclusion

The results provide convincing evidence that M2e-specific Ab-mediated protection is currently lacking or suboptimal in humans.
The Effect of a Fat‐Enriched Diet on the Pattern of Distribution of Pancreatic Islet Cells in the C57BL/6J Mice
Authors: ADEGHATE ERNEST , CHRISTOPHER HOWARTH FRANK , RASHED HAMEED , SAEED TARIQ , GBEWONYO AMSTRONG
Published: December 2006

Abstract:  The C57BL/6J mice are inbred strains and develop the metabolic syndrome of obesity, hyperinsulinemia, hyperglycemia, and hypertension, when fed a high‐fat diet. These features are similar to those observed in the human metabolic syndrome. This article examined the effect of fat‐enriched (FE) diet on the pattern of distribution of insulin‐, glucagon‐, somatostatin‐, and pancreatic polypeptide (PP)‐positive cells in the pancreatic islets of C57BL/6J mice using immunohistochemical methods. Insulin‐immunoreactive cells were observed in both the peripheral and central regions of the islets of Langerhans in both FE‐ and control diet‐fed mice. The percentage distribution of insulin‐positive cells was similar in FE (83.5 ± 6.4) compared to control diet‐fed C57BL/6J mice (83.8 ± 6.5). Glucagon‐containing cells were discerned in the periphery of pancreatic islets in both FE‐ and control diet‐fed mice. The percentage distribution of glucagon was not statistically different in mice fed with FE (9.9 ± 2.7) compared to control diet (11.3 ± 4.9). Somatostatin‐positive cells were seen in the outer part of the islet of Langerhans and constitute 12.1% (±6.3) and 10% (±5.5) of pancreatic islet cells in FE‐ and control diet‐fed mice, respectively. PP‐immunoreactive cells were observed in the peripheral region of the pancreatic islets of both FE‐ and control diet‐fed mice. The percentage distribution of PP‐positive cells was significantly (2.0 ± 1.2) lower compared to control (5.1 ± 2.4). In conclusion, the number of PP is significantly reduced in FE diet‐fed mice and may play a role in the pathogenesis of diet‐induced metabolic syndrome in C57BL/6J mice.
Effects of Brain Natriuretic Peptide on Contraction and Intracellular Ca2+ in Ventricular Myocytes from the Streptozotocin‐Induced Diabetic Rat
Authors: HOWARTH FRANK C. , SHAMSI NOURA AL , QAYDI MARYAM AL , MAZROUEI MARIAM AL , QURESHI ANWAR , CHANDRANATH S.I. , KAZZAM ELSADIG , ADEM ABDU
Published: December 2006

Abstract:  The streptozotocin (STZ)‐treated rat is a widely studied experimental model of diabetes mellitus (DM). Its pathophysiology includes hypoinsulinemia, hyperglycemia, cardiac hypertrophy, and a cardiomyopathy that is characterized by the presence of diastolic and/or systolic contractile dysfunction. As part of their endocrine function cardiomyocytes in the heart produce and secrete a family of related peptide hormones called the natriuretic peptides that include A‐type natriuretic peptide (ANP) and B‐type natriuretic peptide (BNP). ANP and BNP levels are variously augmented in patients with hypertension, cardiac overload, in the ventricles of failing or hypertrophied heart, in cardiac heart failure, in acute myocardial infarction (MI), and in some circumstances in DM. In this article, the effects of BNP on ventricular myocyte contraction and Ca2+ transport in STZ‐induced diabetic rats have been investigated. BNP concentration was significantly increased in blood plasma and in atrial muscle in STZ‐induced diabetic rats compared to age‐matched controls. BNP was 11.9 ± 0.9 ng/mL in plasma from diabetic rats compared to 6.7 ± 1.6 ng/mL in controls and 15.8 ± 2.0 ng/mg protein in diabetic atrial muscle compared to 8.5 ± 1.0 ng/mg protein in controls. The heart weight to body weight ratio, an indicator of hypertrophy, was significantly increased in diabetic rat heart (4.3 ± 0.1 mg/g) compared to controls (3.7 ± 0.04 mg/g). The amplitude of shortening was not significantly altered in diabetic myocytes (10.3 ± 0.4%) compared to controls (10.9 ± 0.4%). BNP reduced the amplitude of shortening to a greater extent in diabetic myocytes (8.1 ± 0.6%) compared to controls (10.1 ± 0.4%). The time to peak (TPK) shortening was significantly prolonged in diabetic myocytes (254 ± 8 ms) compared to controls (212 ± 5 ms) and was not additionally altered by BNP. The time to half relaxation of shortening was also significantly prolonged in diabetic myocytes (131 ± 8 ms) compared to controls (111 ± 5 ms). BNP (10−8 to 10−6 M) normalized the time to half relaxation of shortening in diabetic myocytes to that of controls. Time to peak (TPK) shortening of Ca2+ was not different between diabetic and control rats. However, BNP (10−7 M) increases TPK of Ca2+ significantly. The amplitude of the Ca2+ transient was significantly increased in diabetic myocytes (0.42 ± 0.02 Ratio units [RU]
) compared to controls (0.36 ± 0.02 RU) and was not additionally altered by BNP. BNP may have a protective role in STZ‐induced diabetic rat heart.
Audit of Pregnancies Complicated by Diabetes from One Center Five Years Apart with Selective versus Universal Screening
Authors: EZIMOKHAI M. , JOSEPH ANNIE , BRADLEY‐WATSON P.
Published: December 2006

Abstract:  The article compares the effect of selective and universal screening on detection rate and outcomes of pregnancies complicated by diabetes mellitus (DM) in a multiethnic population. The method used was to review the pregnancy and delivery of two 18‐month periods, 5 years apart. In the year 1996–1997 when selective screening was used 315 (5.7%) of 5506 delivered women had diabetes during pregnancy. The rates of diabetes in the different ethnic groups were: UAE (4.4%), Peninsula Arabs (4.0%), Chami Arabs (4.5%), North African Arabs (6.7%), Indian subcontinent (7.5%), and Somalis and Sudanese (9.7%)
. The rate of diabetes among the different ethnic groups for the year 2001–2002 when screening was universal but diagnosis made by the same criteria were 590 (9.7%) of 6232 delivered women, UAE (9.2%), Peninsula Arabs (8.4%), Chami Arabs (8.2%), North African Arabs (9.6%), Indian Subcontinent (11.0%), Somalis and Sudanese (11.3%). The outcome indicators and their rates in the years 1996–1997 and 2001–2002 were respectively: gestational diabetes, 86.3%, 89.0%; requirement of insulin treatment, 74.3% 82.5%; vaginal delivery, 68.2%, 75.3%; cesarean section, 30.3%, 19.8%; macrosomia, 22.2%, 6.7%; intrauterine fetal death, 2.9%, 1.1%; and preterm delivery, 22.5%, 17.5%. This article confirms the influence of ethnic background on the prevalence of gestational diabetes in a multiethnic and multicultural society. Over a period of 5 years, there was a 66.7% increase in the incidence of gestational diabetes, which was probably due to a combination of increased detection by change in screening policy and an increase in the incidence of gestational diabetes. The indicators of disease severity and control, such as insulin requirement, rates of abdominal delivery, macrosomia, and structural congenital malformations, were significantly better in a cohort identified by universal screening compared with that identified by selective screening. Universal screening seems to be a more appropriate strategy for screening in this environment.
Calpains and Their Multiple Roles in Diabetes Mellitus
Authors: HARRIS FREDERICK , BISWAS SUMAN , SINGH JAIPAUL , DENNISON SARAH , PHOENIX DAVID A.
Published: December 2006

Abstract:  Type 2 diabetes mellitus (T2DM) can lead to death without treatment and it has been predicted that the condition will affect 215 million people worldwide by 2010. T2DM is a multifactorial disorder whose precise genetic causes and biochemical defects have not been fully elucidated, but at both levels, calpains appear to play a role. Positional cloning studies mapped T2DM susceptibility to CAPN10, the gene encoding the intracellular cysteine protease, calpain 10. Further studies have shown a number of noncoding polymorphisms in CAPN10 to be functionally associated with T2DM while the identification of coding polymorphisms, suggested that mutant calpain 10 proteins may also contribute to the disease. Here we review recent studies, which in addition to the latter enzyme, have linked calpain 5, calpain 3, and its splice variants, calpain 2 and calpain 1 to T2DM‐related metabolic pathways along with T2DM‐associated phenotypes, such as obesity and impaired insulin secretion, and T2DM‐related complications, such as epithelial dysfunction and diabetic cataract.