bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of Glycogen Synthase Kinase 3β Disrupts the Binding of Hexokinase II to Mitochondria by Phosphorylating Voltage-Dependent Anion Channel and Potentiates Chemotherapy-Induced Cytotoxicity
Authors: Pastorino John G. , Hoek Jan B. , Shulga Nataly 
Published: November 2005

AbstractTransformed cells are highly glycolytic and overexpress hexokinase II (HXK II). HXK II is capable of binding to the mitochondria through an interaction with the voltage-dependent anion channel (VDAC), an abundant outer mitochondrial membrane protein. The binding of HXK II to mitochondria has been shown to protect against loss of cell viability. Akt activation inhibits apoptosis partly by promoting the binding of HXK II to the mitochondria, but the mechanism through which Akt accomplishes this has not been characterized. The present report shows that Akt mediates the binding of HXK II to the mitochondria by negatively regulating the activity of glycogen synthase kinase 3β (GSK3β). On inhibition of Akt, GSK3β is activated and phosphorylates VDAC. HXK II is unable to bind VDAC phosphorylated by GSK3β and dissociates from the mitochondria. Inhibition of Akt potentiates chemotherapy-induced cytotoxicity, an effect that is dependent on GSK3β activation and its attendant ability to disrupt the binding of HXK II to the mitochondria. Moreover, agents that can force the detachment of HXK II from mitochondria in the absence of Akt inhibition or GSK3β activation promoted a synergistic increase in cell killing when used in conjunction with chemotherapeutic drugs. Such findings indicate that interference with the binding of HXK II to mitochondria may be a practicable modality by which to potentiate the efficacy of conventional chemotherapeutic agents.
Some Oral Poliovirus Vaccines Were Contaminated with Infectious SV40 after 1961
Authors: Cutrone Rochelle , Lednicky John , Dunn Glynis , Rizzo Paola , Bocchetta Maurizio , Chumakov Konstantin , Minor Philip , Carbone Michele 
Published: November 2005

Abstract
Some polio vaccines prepared from 1954 to 1961 were contaminated with infectious SV40. It has been assumed that all polio vaccines were SV40 free in the United States after 1961 and in other countries after 1962. Following a WHO requirement that was prompted by the detection of SV40 in some human tumors, we conducted a multilaboratory study to test for SV40 polio vaccines prepared after 1961. Vaccine samples from 13 countries and the WHO seed were initially tested by PCR. The possible presence of intact and/or infectious SV40 DNA in PCR-positive samples was tested by transfection and infection of permissive CV-1 cells. All results were verified by immunohistochemistry, cloning, and sequencing. All the vaccines were SV40 free, except for vaccines from a major eastern European manufacturer that contained infectious SV40. We determined that the procedure used by this manufacturer to inactivate SV40 in oral poliovirus vaccine seed stocks based on heat inactivation in the presence of MgCl2 did not completely inactivate SV40. These SV40-contaminated vaccines were produced from early 1960s to about 1978 and were used throughout the world. Our findings underscore the potential risks of using primary monkey cells for preparing poliovirus vaccines, because of the possible contamination with SV40 or other monkey viruses, and emphasize the importance of using well-characterized cell substrates that are free from adventitious agents. Moreover, our results indicate possible geographic differences in SV40 exposure and offer a possible explanation for the different percentage of SV40-positive tumors detected in some laboratories.
The Differential Effects of Mutant p53 Alleles on Advanced Murine Lung Cancer
Authors: Jackson Erica L. , Olive Kenneth P. , Tuveson David A. , Bronson Roderick , Crowley Denise , Brown Michael , Jacks Tyler 
Published: November 2005

Abstract
We report a direct comparison of the differential effects of individual p53 mutations on lung tumor growth and progression, and the creation of a murine model of spontaneous advanced lung adenocarcinoma that closely recapitulates several aspects of advanced human pulmonary adenocarcinoma. We generated compound conditional knock-in mice with mutations in K-ras combined with one of three p53 alleles: a contact mutant, a structural mutant, or a null allele. p53 loss strongly promoted the progression of K-ras–induced lung adenocarcinomas, yielding a mouse model that is strikingly reminiscent of advanced human lung adenocarcinoma. The influence of p53 loss on malignant progression was observed as early as 6 weeks after tumor initiation. Furthermore, we found that the contact mutant p53R270H, but not the structural mutant p53R172H, acted in a partially dominant-negative fashion to promote K-ras–initiated lung adenocarcinomas. However, for both mutants, loss-of-heterozygosity occurred uniformly in advanced tumors, highlighting a residual tumor-suppressive function conferred by the remaining wild-type allele of p53. Finally, a subset of mice also developed sinonasal adenocarcinomas. In contrast to the lung tumors, expression of the point-mutant p53 alleles strongly promoted the development of sinonasal adenocarcinomas compared with simple loss-of-function, suggesting a tissue-specific gain-of-function.
Epigenetic Transdifferentiation of Normal Melanocytes by a Metastatic Melanoma Microenvironment
Authors: Seftor Elisabeth A. , Brown Kevin M. , Chin Lynda , Kirschmann Dawn A. , Wheaton William W. , Protopopov Alexei , Feng Bin , Balagurunathan Yoganand , Trent Jeffrey M. , Nickoloff Brian J. , Seftor Richard E.B. , Hendrix Mary J.C. 
Published: November 2005

Abstract
The clinical management of cutaneous melanoma would benefit significantly from a better understanding of the molecular changes that occur during melanocytic progression to a melanoma phenotype. To gain unique insights into this process, we developed a three-dimensional in vitro model that allows observations of normal human melanocytes interacting with a metastatic melanoma matrix to determine whether these normal cells could be reprogrammed by inductive cues in the tumor cell microenvironment. The results show the epigenetic transdifferentiation of the normal melanocytic phenotype to that of an aggressive melanoma-like cell with commensurate increased migratory and invasive ability with no detectable genomic alterations. Removal of the transdifferentiated melanocytes from the inductive metastatic melanoma microenvironment results in a reversion to their normal phenotype. However, a normal melanocyte microenvironment had no epigenetic influence on the phenotype of metastatic melanoma cells. This novel approach identifies specific genes involved in the transdifferentiation of melanocytes to a more aggressive phenotype, which may offer significant therapeutic value.
Mechanisms of Inactivation of the Receptor Tyrosine Kinase EPHB2 in Colorectal Tumors
Authors: Alazzouzi Hafid , Davalos Veronica , Kokko Antti , Domingo Enric , Woerner Stefan M. , Wilson Andrew J. , Konrad Lars , Laiho Päivi , Espín Eloi , Armengol Manel , Imai Kohzoh , Yamamoto Hiroyuki , Mariadason John M. , Gebert Johannes F. , Aaltonen Lauri A. , Schwartz Simo , Arango Diego 
Published: November 2005

Abstract
The receptor tyrosine kinase EPHB2 has recently been shown to be a direct transcriptional target of TCF/β-catenin. Premalignant lesions of the colon express high levels of EPHB2 but the expression of this kinase is reduced or lost in most colorectal carcinomas. In addition, inactivation of EPHB2 has been shown to accelerate tumorigenesis initiated by APC mutation in the colon and rectum. In this study, we investigated the molecular mechanisms responsible for the inactivation of EPHB2 in colorectal tumors. We show here the presence of mutations in repetitive sequences in exon 17 of EPHB2 in 6 of 29 adenomas with microsatellite instability (MSI), and 101 of 246 MSI carcinomas (21% and 41%, respectively). Moreover, we found EPHB2 promoter hypermethylation in 54 of the 101 colorectal tumors studied (53%). Importantly, EPHB2 expression was restored after treatment of EPHB2-methylated colon cancer cells with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine. In conclusion, in this study, we elucidate the molecular mechanisms of inactivation of EPHB2 and show for the first time the high incidence of frameshift mutations in MSI colorectal tumors and aberrant methylation of the regulatory sequences of this important tumor suppressor gene.
Induction of Renal Tumorigenesis with Elevated Levels of Somatic Loss of Heterozygosity in Tsc1+/- Mice on a Blm-Deficient Background
Authors: Wilson Catherine , Idziaszczyk Shelley , Colley James , Humphreys Vikki , Guy Carol , Maynard Julie , Sampson Julian R. , Cheadle Jeremy P. 
Published: November 2005

Abstract
A Bloom's deficient mouse model (Blmm3/m3) has been shown to induce colorectal tumorigenesis when crossed with Apc+/Min mice. Here, we investigated whether the Blmm3/m3 genotype could induce tumorigenesis in extracolonic tissues in tuberous sclerosis 1–deficient (Tsc1+/−) mice that are predisposed to renal cystadenomas and carcinomas. Genotyping of offspring from Tsc1+/− Blm+/m3 intercrosses showed that a ∼24% excess of Tsc1+/− over Tsc1+/+ mice died before weaning (P = 0.016), although Blm deficiency had no cumulative effect on Tsc1+/− survival. Tsc1+/− Blmm3/m3 mice had significantly more macroscopic and microscopic renal lesions at 3 to 6 months compared with Tsc1+/− Blm+/m3 mice (P =0.0003 and 0.0203, respectively), and their tumors showed significantly increased levels of somatic loss of heterozygosity (LOH) of the wild-type Tsc1 (Tsc1wt) allele compared with those from Tsc1+/− Blm+/+ mice (P &lt; 0.0001). Tsc1+/− Blm+/m3 mice did not show significantly more renal lesions compared with Tsc1+/− Blm+/+ animals; however, their lesions still showed significantly increased levels of somatic LOH of the Tsc1wt allele (P = 0.03). Ninety-five percent (19 of 20) of lesions from Tsc1+/− Blm+/m3 mice retained the wild-type Blm (Blmwt) allele, indicating that the increased somatic LOH at Tsc1 was mediated by Blm haploinsufficiency. Renal lesions from a Blm-deficient background stained positively with anti-phospho-S6 ribosomal protein (Ser240/244), suggesting that these lesions develop through the normal pathway of Tsc-associated tumorigenesis. This work shows the use of the Blmm3/m3 mice for inducing renal tumorigenesis, and the high levels (∼87%) of LOH in the resultant tumors will help facilitate mapping of loci involved in tumor progression.
Helminth communities of two lizard populations (Lacertidae) from Canary Islands (Spain): Host diet-parasite relationships
Authors: Roca Vicente , Carretero Miguel A. , Llorente Gustavo A. , Montori Albert , Martin Juan E. 
Published: November 2005

Abstract
A parasitological survey has been carried out to determine the relationships
between host diet and parasite fauna. Diet, and infracommunities and
component communities of two subspecies of lacertid lizards, Gallotia
galloti galloti (Oudart, 1839) and G. g. palmae (Boettger et Müller, 1914)
from Tenerife and La Palma islands (Canary Islands, Spain), have been
analysed. High values of parasite infection parameters were found in both
subspecies, which were only infected by nematodes of the family
Pharyngodonidae. Plant matter was mainly consumed by both lizard subspecies
and relevant amounts of mineral matter were also found in both hosts. Diet
of these lacertid lizards was correlated with their parasite fauna formed by
monoxenous nematodes parasitising herbivorous reptiles, as in tortoises and
iguanid lizards. Abundance and richness of parasites increased with
consumption of plant matter in G. g. galloti. Helminthological data support
the idea of a tendency of both hosts towards herbivory, probably related to
their own phylogeny linked to insularity.
Description of the tadpoles of Boophis doulioti and B. xerophilus from Western Madagascar with notes on larval life history and breeding ecology
Authors: Glos Julian , Linsenmair K. Eduard 
Published: November 2005

AbstractThe genus Boophis is very diverse in species number and ecology within the endemic Malagasy family Mantellidae. Two species, Boophis doulioti and B. xerophilus, stand out as they are breeding in stagnant waters in the dry west and south of Madagascar, while the large majority are specialized to breeding in brooks of the rainforests in the east. In this paper the morphology, larval life history, ecology of the sympatric tadpoles and some aspects of the breeding ecology of B. doulioti and B. xerophilus are described. Tadpoles of the two species differ in many morphological characters and proportions, with differing positions of the eyes and body coloration being the most prominent. There is a considerable temporal and spatial overlap in the choice of breeding ponds by both species in the study area. However, B. xerophilus tadpoles are restricted to larger and more permanent breeding ponds while the generalistic B. doulioti uses also smaller and more ephemeral water bodies. Variability in larval life history traits of B. doulioti individuals growing up in ephemeral ponds compared to those from more permanent ponds indicates considerable developmental plasticity in tadpole life history of this species.
Null models and the thermal biology of the anguid lizard Anguis fragilis; evidence for thermoregulation?
Authors: Meek Roger 
Published: November 2005

AbstractObservations were made on the behaviour and body temperatures of the legless lizard Anguis fragilis when active above ground in outdoor enclosures. The lizards were most frequently observed in partially shaded locations followed by fully shaded areas; full basking and locomotory movement were minor activities irrespective of weather conditions. Weather conditions had no significant influence on behaviour. Tests for thermoregulation using null models indicated that the main reason for movement above ground was thermoregulatory. Body temperatures were significantly higher than shade operative temperatures but lower than operative temperatures in open locations whatever the weather. Standard deviations in body temperature, employed as a measure of thermoregulatory precision, were lower than standard deviations of operative temperatures in sunny weather but not significantly different from operative temperatures during overcast weather or shaded operative temperatures during sunny weather. The limited amount of locomotory movement suggests thermoregulation was achieved through selection of appropriate microenvironments.
Translational Research Principles of an Effectiveness Trial for Diabetes Care in an Urban African American Population
Authors: Gary Tiffany L. , Hill-Briggs Felicia , Batts-Turner Marian , Brancati Frederick L. 
Published: November 2005

Purpose Large-scale effectiveness trials designed to translate evidence-based diabetes care to community settings are few. Studies describing these methods among high-risk minority populations are particularly limited. Methods The authors describe Project Sugar, a randomized controlled trial conducted in 2 phases: Project Sugar 1 (1994-1999), which piloted a 4-arm clinic and homebased intervention using nurse case management and community health workers in 186 urban African Americans with type 2 diabetes, and Project Sugar 2 (2000-2005), which examined effectiveness of this intervention among 542 diabetic, urban African Americans. Results and Conclusions Project Sugar had success with regard to recruitment and retention, both in phase 1 (80% rate at 24 months) and phase 2 (>90% at 24 months). Using the RE-AIM framework, planning and research design for Project Sugar 2 is described in detail for elements that contributed to the reach, effectiveness, adoption, implementation, and maintenance of this study within a minority community setting. In addition to successful strategies, challenges to conducting effectiveness trials in an inner-city African American community are identified.
Variations on a theme
Authors: Kauffman Nils 
Published: November 2005

English This article compares the International Baccalaureate Primary Years Programme (IBPYP) as implemented at three schools in the USA. The author hypothesizes that the schools each offer a unique form of the program based on the respective context and capacity to implement the IBPYP. The author found consistency among the faculties in their explanation of key components of the program. Variation existed in the implementation of these concepts. The author concludes that this variation is due to the different contexts of implementation and to the ambiguity inherent in the IBPYP. French Cette étude compare la mise en oeuvre du Programme primaire (PP) de l'Organisation du Baccalauréat International (IBO) dans trois établissements scolaires aux États-Unis. L'auteur émet l'hypothèse que chacun d'eux propose une forme unique de ce programme basée sur leur contexte respectif et leur capacité à le mettre en oeuvre. L'auteur a découvert une certaine cohérence dans les explications que le corps enseignant de chacun de ces établissements donnait des éléments clés du programme. Il existait toutefois des différences dans la mise en oeuvre de ces concepts. L'auteur conclut que ces variations sont dues aux différents contextes de mise en oeuvre et à l'ambiguïté inhérente au PP. Spanish Este estudio compara cómo tres colegios en Estados Unidos implementan el Programa de la Escuela Primaria (PEP) de la Organización del Bachillerato Internacional. La hipótesis del autor es que cada colegio tiene una forma propia y única de ofrecer el programa, en función de su contexto y de su capacidad. El autor observó coherencia en la explicación de los componentes clave del programa dada por los docentes de los tres colegios. También observó diferencias en su implementación de estos conceptos. El autor concluye que estas diferencias se deben a los distintos contextos de implementación y a la ambigu¨edad inherente al PEP.
Present and future teachers of the world’s children
Authors: Duckworth Rebecca L. , Levy Lynn Walker , Levy Jack 
Published: November 2005

English The purpose of the study was to investigate the ‘international mindedness’ (IM) of a group of pre- and in-service international school teachers. This included an analysis of their beliefs about teaching and learning successfully in international settings. Ninety respondents completed a 55-item survey, eight of whom then participated in eight-item interviews. Results were multifold; most notably demographics of this group tended to vary while teaching beliefs and international mindedness remained relatively similar. This may suggest that many present and future international educators, while somewhat diverse, share many values and beliefs. French Cette étude avait pour but d'étudier la 'sensibilité internationale' d'un groupe d'enseignants avant et après qu'ils n'aient commencé à travailler dans un établissement scolaire international. Elle comprend une analyse de leurs convictions concernant la réussite de l'enseignement et de l'apprentissage dans un cadre international. Une enquête, composée de 55 questions, a été effectuée auprès de 90 personnes, dont huit ont ensuite participé à un entretien de huit questions. Les résultats ont révélé plusieurs éléments: alors que la plupart des données démographiques de ce groupe avaient tendance à varier, leur sensibilité internationale et leurs convictions concernant l'enseignement restaient relativement similaires. Cette constatation peut suggérer que de nombreux professionnels de l'éducation présents et futurs, bien que d'horizons différents, partagent les mêmes valeurs et convictions. Spanish El propósito de este estudio era investigar sobre la 'mentalidad internacional' de un grupo de profesores de colegios internacionales y profesores que iban a comenzar a trabajar en colegios internacionales. El estudio incluía un ana´lisis de sus creencias sobre lo que constituye una enseñanza y un aprendizaje adecuados en contextos internacionales. Noventa profesores respondieron a una encuesta de 55 preguntas, y ocho de ellos participaron después en una entrevista de 8 preguntas. Los resultados fueron muy diversos; en especial, la demografía del grupo variaba, pero la mentalidad internacional y las creencias sobre la enseñanza eran relativamente similares. Estos resultados pueden sugerir que muchos educadores internacionales actuales y futuros, si bien con cierta diversidad, comparten numerosos valores y creencias.
International education
Authors: James Kieran 
Published: November 2005

English This article explores the rationale for, aims of, and values underpinning ‘international education’, discusses its ‘characteristic’ features of ‘world-mindedness’ and ‘international understanding’, and considers whether these are achieved through the study of ‘international curricula’. It examines the term ‘international education’, and its field, in the light of the current, post-9/11 socio-political situation in a number of countries. It is argued that few of the values espoused in its name are exclusively internationalist in ethos, or universally-held, that the term is thus misleading in advocating all of them, and that it may therefore be reaching the end of its useful life. French Cet article explore les fondements, les objectifs et les valeurs à la base de l''éducation internationale', discute de ses aspects 'caractéristiques' à savoir la 'sensibilité internationale' et la 'compréhension internationale' et considère si celles-ci sont atteintes par le biais de 'programmes d'études internationaux'. L'article examine également le syntagme 'éducation internationale', ainsi que ses domaines, dans le contexte socio-politique actuel de 'l'après 11 septembre' dans un certain nombre de pays. Il y est avancé que très peu des valeurs embrassées en son nom relèvent d'une philosophie exclusivement internationaliste ou sont universellement partagées, qu'en se revendiquant de toutes ces valeurs, ce syntagme est trompeur et qu'il a donc peut-être atteint la fin de sa durée de vie utile. Spanish Este artículo explora los principios, los objetivos y los valores que constituyen la base de la 'educación internacional', analiza sus aspectos 'característicos' a saber, la 'mentalidad internacional' y el 'entendimiento internacional' y cuestiona si éstos se logran por medio del estudio de 'currículos internacionales'. El artículo examina el sintagma 'educación internacional', así como el a´mbito que representa, en el contexto socio-político actual (posterior al 11 de septiembre de 2001) en diversos países. El autor arguye que pocos de los valores asociados a dicho sintagma derivan de una filosofía exclusivamente internacionalista o son universalmente compartidos, y que, por tanto, al reivindicar todos los valores, el sintagma es engañoso y puede, por ello, estar acerca´ndose al final de su vida útil.
School culture
Authors: Poore Paul 
Published: November 2005

English This article considers the issue of school culture within the context of international schools worldwide. Focusing on three main points - cultural differences, educating the human spirit, and the importance of relationships - a number of challenges are raised for the international educator and, especially, for the leaders of such schools. French Cet article explore le thème de la culture scolaire dans le contexte d'écoles internationales à travers le monde. En se concentrant sur trois points essentiels - les différences culturelles, l'éducation de l'esprit humain et l'importance des rapports humains - il soulève des défis pour les éducateurs internationaux, particulièrement pour les chefs de tels établissements scolaires. Spanish En este artículo se analiza el tema de la cultura del colegio en el contexto de los colegios internacionales en distintas partes del mundo. Se concentra en tres puntos principales: diferencias culturales, la educación del espíritu humano y la importancia de las relaciones. A través de ellos, se plantea una serie de desafíos que deben enfrentar los educadores en los colegios internacionales y, en especial, quienes se encuentran al frente de este tipo de colegio.