Structural analysis of p185c-neu and epidermal growth factor receptor tyrosine kinases: oligomerization of kinase domains.

The epidermal growth factor receptor (EGFR) and p185c-neu proteins associate as dimers to create an efficient signaling assembly. Overexpression of these receptors together enhances their intrinsic kinase activity and concomitantly results in oncogenic cellular transformation. The ectodomain is able to stabilize the dimer, whereas the kinase domain mediates biological activity. Here we analyze potential interactions of the cytoplasmic kinase domains of the EGFR and p185c-neu tyrosine kinases by homology molecular modeling. This analysis indicates that kinase domains can associate as dimers and, based on intermolecular interaction calculations, that heterodimer formation is favored over homodimers. The study also predicts that the self-autophosphorylation sites located within the kinase domains are not likely to interfere with tyrosine kinase activity, but may regulate the selection of substrates, thereby modulating signal transduction. In addition, the models suggest that the kinase domains of EGFR and p185c-neu can undergo higher order aggregation such as the formation of tetramers. Formation of tetrameric complexes may explain some of the experimentally observed features of their ligand affinity and hetero-receptor internalization.

Neoplastic development: paradoxical relation between impaired cell growth at low population density and excessive growth at high density.

The role of heritable, population-wide cell damage in neoplastic development was studied in the 28 L subline of NIH 3T3 cells. These cells differ from the 17(3c) subline used previously for such studies in their lower frequency of "spontaneous" transformation at high population density and their greater capacity to produce large, dense transformed foci. Three cultures of the 28 L subline of NIH 3T3 cells were held under the constraint of confluence for 5 wk (5 wk 1 degree assay) and then assayed twice in succession (2 degrees and 3 degrees assays) for transformed foci and saturation density. After the 2 degrees assay, the cells were also passaged at low density to determine their exponential growth rates and cloned to determine the size and morphological features of the colonies. Concurrent measurements were made in each case with control cells that had been kept only in frequent low-density passages and cells that had been kept at confluence for only 2 wk (2 wk 1 degree). Two of the three cultures transferred from the 2 degrees assay of the 5 wk 1 degree cultures produced light transformed foci, and the third produced dense foci. The light focus-forming cultures grew to twice the control saturation density in their 2 degrees assay and 6-8 times the control density in the 3 degrees assay; saturation densities for the dense focus formers were about 10 times the control values in both assays. All three of the cultures transferred from the 2 degrees assay of the 5 wk 1 degree cultures multiplied at lower rates than controls at low densities, but the dense focus formers multiplied faster than the light focus formers. The reduced rates of multiplication of the light focus formers persisted for > 50 generations of exponential multiplication at low densities. Isolated colonies formed from single cells of the light focus formers were of a lower population density than controls; colonies formed by the dense focus formers were slightly denser than the controls but occupied only half the area. A much higher proportion of the colonies from the 5 wk 1 degree cultures than the controls consisted of giant cells or mixtures of giant and normal-appearing cells. The results reinforce the previous conclusion that the early increases in saturation density and light focus formation are associated with, and perhaps caused by, heritable, population-wide damage to cells that is essentially epigenetic in nature. The more advanced transformation characterized by large increases in saturation density and dense focus formation could have originated from rare genetic changes, such as chromosome rearrangements, known to occur at an elevated frequency in cells destabilized by antecedent cellular damage.

Induction of cell proliferation in mammalian inner-ear sensory epithelia by transforming growth factor alpha and epidermal growth factor.

Regenerative proliferation occurs in the inner-ear sensory epithelial of warm-blooded vertebrates after insult. To determine how this proliferation is controlled in the mature mammalian inner ear, several growth factors were tested for effects on progenitor-cell division in cultured mouse vestibular sensory epithelia. Cell proliferation was induced in the sensory epithelium by transforming growth factor alpha (TGF-alpha) in a dose-dependent manner. Proliferation was also induced by epidermal growth factor (EGF) when supplemented with insulin, but not EGF alone. These observations suggest that stimulation of the EGF receptors by TGF-alpha binding, or EGF (plus insulin) binding, stimulates cell proliferation in the mature mammalian vestibular sensory epithelium.

Is Diversity Inclusiveness?" A Personal and Empirical Exploration"

While psychology recognizes and celebrates multicultural diversity connoting the inclusivity of all, it seems to ignore sociopolitical and religious diversity. Within contemporary multiculturalism, conservative voices are often found wanting. In this study, a "liberal" privilege survey was developed to examine the inclusion and limits of conservative ideology within the multicultural paradigm of psychology training programs and workplaces. It was hypothesized that mental health professionals who identified as more conservative would express more oppression of views/values in their workplace than individuals who did not identify as being conservative and those who identified as more liberal would express bias and concerns against those holding conservative views. Results did not support an overall generalization of conservative bias or intolerance, but did provide some evidence of discontent among individuals holding more conservative religious and sociopolitical values. Overall, findings reinforce the need for gathering more data on sociopolitical and religious variables within the context of multiculturalism and broadening the dialogue on diversity issues surrounding sociopolitical views and bias among colleagues and in training programs.

Our Lady of Guadalupe : contemporary explorations of personal and cultural identity

Since it first appeared, the image of Our Lady of Guadalupe has remained relatively unchanged. In the last thirty-five years, however, this has been changing. Artists are creating new variations of the icon to represent and express their reinterpretations. In some of these more contemporary images, the figure of Guadalupe has changed dramatically, but still retains enough traditional elements to be easily recognizable. Some of these images have been received with mixed results and have even sparked major controversy. These new, and sometimes controversial depictions of Guadalupe, specifically those created by Ester Hernández, Yolanda M. López and Alma López, will be explored here. Although each artist has her own individual motivations and intentions, all of the images presented here explore personal and cultural identity, as well as seek in some way to honor ordinary, human women through the sacred iconography of Our Lady of Guadalupe.

La mediación universitaria: un recurso de orientación. Experiencia en la Universidad de Alicante

Este trabajo de investigación parte del concepto de orientación que compartimos con Bisquerra (2008), definiéndola como un proceso de ayuda continuo a todas las personas, en todos los aspectos, con la finalidad de potenciar el desarrollo humano a lo largo de toda la vida. En este marco de referencia caben todas las acciones dirigidas hacia quien necesita y busca apoyo para su crecimiento personal, académico y profesional. En el ámbito universitario, históricamente poco receptivo a este tipo de actuaciones, se vienen generalizando a raíz de las nuevas concepciones metodológicas que exige la convergencia europea conceptos novedosos e innovadores y que avalan la orientación en la Universidad, como tutorización, transición universitaria, o mediación. Y son ya muchas instituciones las que han puesto en marcha organismos y programas de innovación para su desarrollo efectivo. La Universidad de Alicante viene trabajando en estos temas desde hace unos años y una de las experiencias más novedosas la desarrolla la Facultad de Educación, implantando la figura de la mediadora como recurso de resolución de situaciones conflictivas. En el marco de esta innovación nos planteamos abordar qué se entiende por mediación y cuál es su funcionalidad, al tiempo que realizar una reflexión sobre los agentes implicados y las competencias necesarias para su implementación. Ha participado en la investigación un grupo de alumnas solicitantes del recurso y un equipo docente constituido en Red de investigación. De los resultados obtenidos en la búsqueda de delimitación conceptual y funcional, de estrategias de gestión y de propuestas de actuación en el proceso mediador podemos concluir que es un aspecto positivo y necesario que rentabiliza las tareas de gestión universitaria y que soluciona al alumnado situaciones que pueden entorpecer un desarrollo personal y académico adecuado.

Technology diffusion, services, and endogenous growth in Europe. Is the Lisbon Strategy still alive? Bruges European Economic Research (BEER) Papers 2/May 2005

We explore the role of business services in knowledge accumulation and growth and the determinants of knowledge diffusion including the role of distance. A continuous time model is estimated on several European countries, Japan, and the US. Policy simulations illustrate the benefits for EU growth of the deepening of the single market, the reduction of regulatory barriers, and the accumulation of technology and human capital. Our results support the basic insights of the Lisbon Agenda. Economic growth in Europe is enhanced to the extent that: trade in services increases, technology accumulation and diffusion increase, regulation becomes both less intensive and more uniform across countries, and human capital accumulation increases in all countries.

Pennsylvania Negro business directory, 1910 : industrial and material growth of the Negroes of Pennsylvania.

Mode of access: Internet.