Regulation of {\it neu\/} gene expression by the simian virus 40 large T antigen and tumor suppressors Rb and p53

The neu gene (also c-erbB-2 or HER2) encodes a 185 kilodalton protein that is frequently overexpressed in breast, ovarian and non-small cell lung cancers. Study of the regulation of neu indicates that neu gene expression can be modulated by c-myc or by the adenovirus 5 E1a gene product. This study demonstrates that the transforming protein, large T antigen, of the simian virus 40 represses neu promoter activity. Repression of neu by large T antigen is mediated through the region $-$172 to $-$79 (relative to first ATG) of the neu promoter--unlike through $-$312 to $-$172 for c-myc or E1a. This suggests a different pathway for repression of neu by large T antigen. The 10 amino acid region of large T required for binding the tumor suppressor, retinoblastoma gene product, Rb, is not necessary for repression of neu. Moreover, the tumor suppressors, Rb and p53 can independently inhibit neu promoter activity. Rb inhibits neu through a 10 base pair G-rich enhancer (GTG element) ($-$243 to $-$234) and also through regions close to transcription initiation sites ($-$172 to $-$79). Mutant Rb unable to complex large T is able to repress the region close to transcription initiation but not the GTG enhancer. Thus, Rb inhibits the two regulatory domains of the neu gene by different mechanisms. Both Rb and p53 can repress the transforming activity of activated neu in focus forming assays. These data provide evidence that tumor suppressors regulate expression of growth stimulatory genes such as neu. Therefore, one reason for the overexpression of neu that is frequently seen in breast cancer cells may be due to functional inactivation of Rb and p53 which is also a common occurrence in breast cancer cells. ^

YKL -40, a vascular -associated serum marker for glioblastoma, correlates with chronic activation of AKT

YKL-40 is a secreted glycoprotein that has been reported to be expressed in pathologic conditions of extracellular matrix degradation and angiogenesis, such as rheumatoid arthritis, severe osteoarthritis, primary colorectal cancer, metastatic breast cancer, and recurrent ovarian cancer (Dehn, Hogdall et al. 2003). ^ We have identified YKL-40 as a serum marker for glioblastoma multiforme (GBM) using microarray analysis from samples of GBM. We compared the gene expression profile of 19 gliomas to pooled normal brain tissue using the Incyte 10,000 gene expression array. The most differentially expressed gene in this analysis was YKL-40; it was detected in GBM samples with a range of 3 to 62-fold elevation over normal brain. Western blot analysis of glioma samples for YKL-40 protein levels revealed substantial elevation in approximately 65% of GBMs, and undetectable levels in lower-grade gliomas and normal brain tissue. ELISA analysis on serum samples of glioma patients showed that YKL-40 levels were substantially elevated in many of the GBM patients. Statistical analysis indicated that in patients with glioma, serum YKL-40 levels correlate with tumor grade and potentially tumor burden in GBM. ^ Furthermore, we found that YKL-40 expression by in-situ hybridization on a brain tumor tissue array was limited to GBM's and gliosarcomas (GSA), and that YKL-40 expression was specific to the GBM component of GSA. Additional in-situ hybridization analysis, found it to be regionally associated with tumor vasculature as well as activated AKT expression in both human and mouse GBM's. Correlation of elevated YKL-40 with phospho-AKT was confirmed by Western blot analysis on a series of glioblastoma tumors, and inhibition of PI3 Kinase signaling by addition of LY294002 also decreased secretion of YKL-40 over a 7-day period in U87 glioblastoma cell tine. Lastly, YKL-40 expression was induced in response to serum starvation and altered by interaction with specific extracellular matrix (ECM) modules. In summary, we have identified the first accurate serum marker for high-grade gliomas. Furthermore, our findings indicate that YKL-40 is a highly expressed vascular-related glycoprotein in human GBM tissue and that it is affected by the AKT signaling pathway and interaction with components of brain ECM proteins. ^

Dinoflagellate cyst assemblages, oxygen isotope records of foraminifera, and alkenone and Mg/Ca-based SST estimates for the time interval 3.40-3.18 Ma (Late Pliocene) from five North Atlantic and Caribbean sediment cores

The early Late Pliocene (3.6 to ~3.0 million years ago) is the last extended interval in Earth's history when atmospheric CO2 concentrations were comparable to today's and global climate was warmer. Yet a severe global glaciation during marine isotope stage (MIS) M2 interrupted this phase of global warmth ~3.30 million years ago, and is seen as a premature attempt of the climate system to establish an ice-age world. Our geochemical and palynological records from five marine sediment cores along a Caribbean to eastern North Atlantic transect show that increased Pacific-to-Atlantic flow via the Central American Seaway weakened the North Atlantic Current (NAC) and attendant northward heat transport prior to MIS M2. The consequent cooling of the northern high latitude oceans permitted expansion of the Greenland ice sheet during MIS M2, despite near-modern atmospheric CO2 concentrations. Before and after MIS M2, heat transport via the NAC was crucial in maintaining warm climates comparable to those predicted for the end of this century.

(Table 1) Potassium, radiogenic Argon 40 and dated age for DSDP Hole 94-608 sediments

K-Ar dates were obtained for three pillow basalt samples recovered from Site 608 (Samples 608-58-1, 103-109 cm; 608-59-1, 3-7 cm; 608-59-1, 48-53 cm). Reliable K-Ar dates cannot be routinely obtained for deep-sea igneous rocks, because they may be subject to inaccuracies related to seawater alteration (Seidemann, 1977, doi:10.1130/0016-7606(1977)88<1660:EOSAOK>2.0.CO;2) and/or the presence of excess radiogenic 40Ar (Dalrymple and Moore, 1968, doi:10.1126/science.161.3846.1132; Dymond, 1970, doi:10.1130/0016-7606(1970)81[1229:EAISBP]2.0.CO;2). Thus, the possibility that the samples dated in this study were subject to these sources of inaccuracy must be evaluated.

Los repositorios institucionales de las universidades como escenarios de la producción intelectual. En: Jornadas Científicotecnológicas 40 aniversario UNaM

Los repositorios institucionales se han transformado en la opción para sacar a la luz la producción intelectual, habida cuenta de que en ellos es posible reunir, publicar, diseminar y preservar la misma. La idea de dar visibilidad a dicha producción genera un sinnúmero de desafíos, tanto para las universidades como para los investigadores; problemas que se pueden resumir en la pérdida del anonimato de los autores; la visibilidad de proyectos similares; la posibilidad de compartir recursos humanos y económicos, entre otros. Esta problemática también está presente en las universidades del NEA1, dado que no cuentan con Repositorios Institucionales que alberguen la producción generada en ellas. El presente proyecto planea reunir los elementos necesarios para presentar un acabado diagnóstico de situación que permita impulsar su concreción para beneficio de la comunidad académica de la región.

Las buenas prácticas docentes en los profesorados universitarios desde la perspectiva del alumnado FHyCS - UNaM. En: Jornadas Científico Tecnológicas 40 aniversario UNaM

La investigación: “Las buenas prácticas de enseñanza que apoyan el ingreso y la permanencia de los estudiantes en los profesorados de la FHyCS-UNaM - Código 16H 330”, atiende dificultades del ingreso y permanencia de los estudiantes universitarios. Hay tres maneras en que las distintas universidades adoptan el problema: despreocuparse, preocuparse u ocuparse. El tema no es nuevo, innovamos el enfoque, al identificar en primer año de cinco profesorados de la FHyCS - UNaM, las “buenas prácticas”, ideadas y aplicadas, por los formadores. Recogimos información utilizando: cuestionarios auto - administrados, observaciones, entrevistas y análisis de dispositivos pedagógicos durante 2011/12, en el presente año procesaremos datos, documentos, opiniones diversas. En esta ponencia caracterizamos las buenas prácticas docentes desde la perspectiva y voz del alumnado de primer año. Al finalizar: a) identificaremos estrategias que favorecen el ingreso; b) aportaremos conocimientos al campo profesional, didáctico y curricular; c) socializaremos hallazgos entre pares; y d) promoveremos las buenas prácticas docentes.