Ligation of cell surface GRP78 with antibody directed against the COOH-terminal domain of GRP78 suppresses Ras/MAPK and PI 3-kinase/AKT signaling while promoting caspase activation in human prostate cancer cells.

We have previously shown that treatment of prostate cancer and melanoma cells expressing GRP78 on their cell surface with antibody directed against the COOH-terminal domain of GRP78 upregulates and activates p53 causing decreased cell proliferation and upregulated apoptosis. In this report, we demonstrate that treatment of 1-LN prostate cancer cells with this antibody decreases cell surface expression of GRP78, Akt(Thr308) and Akt(Ser473) kinase activities and reduces phosphorylation of FOXO, and GSK3beta. This treatment also suppresses activation of ERK1/2, p38 MAPK and MKK3/6; however, it upregulates MKK4 activity. JNK, as determined by its phosphorylation state, is subsequently activated, triggering apoptosis. Incubation of cells with antibody reduced levels of anti-apoptotic Bcl-2, while elevating pro-apoptotic BAD, BAX and BAK expression as well as cleaved caspases-3, -7, -8 and -9. Silencing GRP78 or p53 gene expression by RNAi prior to antibody treatment abrogated these effects. We conclude that antibody directed against the COOH-terminal domain of GRP78 may prove useful as a pan suppressor of proliferative/survival signaling in cancer cells expressing GRP78 on their cell surface.

Experiencias sobre la aproximación intuitiva en geometría. Una aproximación al número Pi en la ESO

En este artículo se presentan algunas experiencias sobre la aproximación intuitiva en geometría y sus implicaciones en el cálculo aproximado del número pi en la ESO. El proceso se gradúa en torno a cuatro actividades. En las dos primeras se aproxima experimentalmente el número Pi y se pretende descubrir el grado de móviles de los alumnos para enfrentarse, desde el punto de vista intuitivo, a los procesos geométricos de aproximación. En las dos últimas se hace una estimación de Pi, en un caso encontrando una secuencia de números irracionales convergente a ese número, y el otro, a partir de una simplificación del método utilizado por Arquímedes, que permite además dar una demostración diferente de la habitual.

Las cifras de pi y el diálogo en el aula

A partir de un artículo publicado en el Faro de Vigo sobre la petisa Wislawa Szymbirska, Premio Nobel de Literatura, en el que se reproduce su poema el número pi se lleva a cabo una experiencia interdisciplinar con el departamento de lengua y literatura, cuya descripción es el objeto de este trabajo.

En el entorno de pi a través de la sección áurea

Mencionados en la relaciones fortuitas o accidentales entre pi y la sección aurea en los textos de autores se supone gran interés una nueva conexión entre ambas constantes que permitirá una aproximación a pi con un desfase de 100 milésimas, en una primera relación, y una segunda aproximación con un desfase de 1000 millonesimas.

El sorprendente número pi

Parece increíble que algo aparentemente tan sencillo como la relación entre la longitud de la circunferencia y su diámetro haya preocupado al hombre desde la más remota antigüedad hasta el presente más actual. A unos, porque han querido aprender sus cifras de memoria y, a otros, porque han querido conocer todas sus cifras con exactitud, lo cierto es que siempre el número pi ha estado presente en el pensamiento de la especie humana.

In vitro-in vivo correlations of self-emulsifying drug delivery systems combining the dynamic lipolysis model and neuro-fuzzy networks

The aim of the current study was to evaluate the potential of the dynamic lipolysis model to simulate the absorption of a poorly soluble model drug compound, probucol, from three lipid-based formulations and to predict the in vitro-in vivo correlation (IVIVC) using neuro-fuzzy networks. An oil solution and two self-micro and nano-emulsifying drug delivery systems were tested in the lipolysis model. The release of probucol to the aqueous (micellar) phase was monitored during the progress of lipolysis. These release profiles compared with plasma profiles obtained in a previous bioavailability study conducted in mini-pigs at the same conditions. The release rate and extent of release from the oil formulation were found to be significantly lower than from SMEDDS and SNEDDS. The rank order of probucol released (SMEDDS approximately SNEDDS > oil formulation) was similar to the rank order of bioavailability from the in vivo study. The employed neuro-fuzzy model (AFM-IVIVC) achieved significantly high prediction ability for different data formations (correlation greater than 0.91 and prediction error close to zero), without employing complex configurations. These preliminary results suggest that the dynamic lipolysis model combined with the AFM-IVIVC can be a useful tool in the prediction of the in vivo behavior of lipid-based formulations.

Fuzzy Coding of Genetic Algorithms

A well-cited paper suggesting fuzzy coding as an alternative to the conventional binary, grey and floating-point representations used in genetic algorithms.

Components of the peptidome and transcriptome persist in lin wa pi: the dried skin of the Heilongjiang brown frog Rana amurensis as used in Traditional Chinese Medicine

Although the ancient practice of traditional Chinese medicine (TCM) utilizes predominantly herbal ingredients, many of which are now the subject of intense scientific scrutiny, significant quantities of animal tissue-derived materials are also employed. Here we have used contemporary molecular techniques to study the material known as lin wa pi, the dried skin of the Heilongjiang brown frog, Rana amurensis, that is used commonly as an ingredient of many medicines, as a general tonic and as a topical antimicrobial/wound dressing. Using a simple technology that has been developed and validated over several years, we have demonstrated that components of both the skin granular gland peptidome and transcriptome persist in this material. Interrogation of the cDNA library constructed from the dried skin by entrapment and amplification of polyadenylated mRNA, using a "shotgun" primer approach and 3'-RACE, resulted in the cloning of cDNAs encoding the precursors of five putative antimicrobial peptides. Two (ranatuerin-2AMa and ranatuerin-2AMb) were obvious homologs of a previously described frog skin peptide family, whereas the remaining three were of sufficient structural novelty to be named amurins 1-3. Mature peptides were each identified in reverse phase HPLC fractions of boiling water extracts of skin and their structures confirmed by MS/MS fragmentation sequencing. Components of traditional Chinese medicines of animal tissue origin may thus contain biologically active peptides that survive the preparation procedures and that may contribute to therapeutic efficacy.