Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion

Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7× and 31.9× coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with β-catenin in colorectal carcinogenesis, the fusion lacks the TCF4 β-catenin-binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events.     

A diffusion model for products with indirect network externalities

This paper develops a new diffusion model that incorporates the indirect network externality. The market with indirect network externalities is characterized by two‐way interactive effects between hardware and software products on their demands. Our model incorporates two‐way interactions in forecasting the diffusion of hardware products based on a simple but realistic assumption. The new model is parsimonious, easy to estimate, and does not require more data points than the Bass diffusion model. The new diffusion model was applied to forecast sales of DVD players in the United States and in South Korea, and to the sales of Digital TV sets in Australia. When compared to the Bass and NSRL diffusion models, the new model showed better performance in forecasting long‐term sales. Copyright © 2008 John Wiley & Sons, Ltd.     

Pleiotropic effects of sonic hedgehog on muscle satellite cells

Muscle satellite cells are believed to form a stable, self-renewing pool of stem cells in adult muscle where they function in tissue growth and repair. A regulatory disruption of growth and differentiation of these cells is assumed to result in tumor formation. Here we provide for the first time evidence that sonic hedgehog (Shh) regulates the cell fate of adult muscle satellite cells in mammals. Shh promotes cell division of satellite cells (and of the related model C2C12 cells) and prevents their differentiation into multinucleated myotubes. In addition, Shh inhibits caspase-3 activation and apoptosis induced by serum deprivation. These effects of Shh are reversed by simultaneous administration of cyclopamine, a specific inhibitor of the Shh pathway. Taken together, Shh acts as a proliferation and survival factor of satellite cells in the adult muscle. Our results support the hypothesis of the rhabdomyosarcoma origin from satellite cells and suggest a role for Shh in this process.Received 23 February 2005; received after revision 2 May 2005; accepted 9 June 2005     

An integrated view of the chemistry and mineralogy of martian soils

The mineralogical and elemental compositions of the martian soil are indicators of chemical and physical weathering processes. Using data from the Mars Exploration Rovers, we show that bright dust deposits on opposite sides of the planet are part of a global unit and not dominated by the composition of local rocks. Dark soil deposits at both sites have similar basaltic mineralogies, and could reflect either a global component or the general similarity in the compositions of the rocks from which they were derived. Increased levels of bromine are consistent with mobilization of soluble salts by thin films of liquid water, but the presence of olivine in analysed soil samples indicates that the extent of aqueous alteration of soils has been limited. Nickel abundances are enhanced at the immediate surface and indicate that the upper few millimetres of soil could contain up to one per cent meteoritic material.     

Prolactin and the ventral prostate gland in juvenile rats

Zusammenfassung Die normalerweise der Hypophysorchidektomie juveniler Ratten folgende Prostataatrophie wurde durch Behandlung mit Progesteron und Prolaktin verhindert. Direkte hypophysäre Einflüsse auf die Prostata werden diskutiert.     

The effect of ATP and carnitine on the endogenous respiration of mitochondria from brown adipose tissue

Zusammenfassung Nachweis der endogenen Atmungsaktivierung von Mitochondrien im braunen Fettgewebe durch ATP und Karnitin. Eine maximale Aktivierung wird bei 6–30 Tage alten Ratten gefunden, während sie in neugeborenen und erwachsenen Tieren kleiner ist. Nur bei den 6–30 Tage alten Tieren hemmt Albumin die Durch ATP und Karnitin erhöhte Atmung.     

Transferrin: Intermolecular iron exchange

Zusammenfassung Die Eisenabgabefähigkeit doppelt beladener Transferrinmoleküle an Retikulozyten, ist jener einfach beladener Moleküle überlegen, und vermindert sich rasch wenn Serum unter physiologischen Bedingungen inkubiert wird. Als Erklärung wird die Neuverteilung von Eisenatomen unter den Transferrinbindungsstellen postuliert.

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This work was supported by Grants from the Swiss National Science Foundation (Grant No. 3.7710.72) and the Hartmann Müller Foundation.