Intratumor MAPK and PI3K signaling pathway heterogeneity in glioblastoma tissue correlates with CREB signaling and distinct target gene signatures.

Limitations in discovering useful tumor biomarkers and drug targets is not only due to patient-to-patient differences but also due to intratumor heterogeneity. Heterogeneity arises due to the genetic and epigenetic variation of tumor cells in response to microenvironmental interactions and cytotoxic therapy. We explored specific signaling pathway activation in glioblastoma (GBM) by investigating the intratumor activation of the MAPK and PI3K pathways.

Xenome--a tool for classifying reads from xenograft samples.

Motivation: Shotgun sequence read data derived from xenograft material contains a mixture of reads arising from the host and reads arising from the graft. Classifying the read mixture to separate the two allows for more precise analysis to be performed.

Results: We present a technique, with an associated tool Xenome, which performs fast, accurate and specific classification of xenograft-derived sequence read data.

G2/M checkpoint gene expression in developing germ cells.

Cell cycle progression is prevented by signal transduction pathways known as checkpoints which are activated in response to replication interference and DNA damage. We cloned a G2/M cell cycle phase-related checkpoint gene from a neonatal mouse testis cDNA library which was identified as mouse claspin, a proposed adaptor protein for Chk1. As part of a study on germ cell differentiation we examined the expression of the checkpoint gene, Chk1, and claspin at 12.

The chromosome 21 transcription factor ETS2 transactivates the beta-APP promoter: implications for Down syndrome.

The gene that codes for beta-amyloid precursor protein (beta-APP), a protein centrally involved in senile plaque formation in Down syndrome (DS) and Alzheimer's disease (AD), is located on chromosome 21. In DS beta-APP expression is three- to fourfold higher than what is expected from the 1.5-fold increased gene load, suggesting that other genes on chromosome 21 directly or indirectly can further up-regulate beta-APP.

Sorsby's fundus dystrophy: what does TIMP3 tell us about general mechanisms underlying macular degeneration?

INTRODUCTION: Mutations in tissue inhibitor of metalloproteinases-3 (TIMP3) gene result in the rare autosomal dominant disease Sorsby's fundus dystrophy (SFD), which shows striking similarities to age-related macular degeneration (ARMD). METHODS: Current research is reviewed and suggests that these mutations result in the accumulation of TIMP3 in Bruch's membrane resulting in decreased turnover of the extracellular matrix and consequent thickening of Bruch's membrane. DNA analysis of ARMD patients has failed to show any significant mutations in the coding-regions of TIMP3.