Transmembrane and Immunoglobulin Domain Containing 1, a Putative Tumor Suppressor, Induces G2/M Cell Cycle Checkpoint Arrest in Colon Cancer Cells.

Colorectal cancer (CRC) is a leading nonfamilial cause of cancer mortality among men and women. Although various genetic and epigenetic mechanisms have been identified, the full molecular mechanisms deriving CRC tumorigenesis are not fully understood. This study demonstrates that cell adhesion molecule transmembrane and immunoglobulin domain containing 1 (TMIGD1) are highly expressed in mouse and human normal intestinal epithelial cells. TMIGD1 knockout mice were developed, and the loss of TMIGD1 in mice was shown to result in the development of adenomas in small intestine and colon. In addition, the loss of TMIGD1 significantly impaired intestinal epithelium brush border membrane, junctional polarity, and maturation. Mechanistically, TMIGD1 inhibits tumor cell proliferation and cell migration, arrests cell cycle at the G2/M phase, and induces expression of p21CIP1 (cyclin-dependent kinase inhibitor 1), and p27KIP1 (cyclin-dependent kinase inhibitor 1B) expression, key cell cycle inhibitor proteins involved in the regulation of the cell cycle. Moreover, TMIGD1 is shown to be progressively down-regulated in sporadic human CRC, and its downregulation correlates with poor overall survival. The findings herein identify TMIGD1 as a novel tumor suppressor gene and provide new insights into the pathogenesis of colorectal cancer and a novel potential therapeutic target.

Pantheon habitat made from regolith, with a focusing solar reflector.

We describe a polar Moon base habitat using direct solar energy for construction, food production and atmospheric revitalization. With a growing area as large as 2000 m2, it could provide for 40 or more people. The habitat is built like the ancient Roman Pantheon, a stone structure with a top circular oculus, bringing in focused sunlight that is spread out to crops below. The conical, corbelled structure is built from cast regolith blocks, held in compression despite the large internal atmospheric pressure by a regolith overlayer 20-30 m thick. It is sealed on the inside against leaks with thin plastic. A solar mirror concentrator used initially to cast the building blocks is later used to illuminate the habitat through a small pressure window at the oculus. Three years of robotic preparation of the building blocks does not seem excessive for a habitat which can be expected to last for millennia, as has the Treasury of Atreus made by similar dry-stone construction. One goal of returning to the Moon is to demonstrate the practicality of long-term human habitation off the Earth. The off-axis, paraboloidal reflecting mirror is rotated about the vertical polar axis in order to direct horizontal sunlight downward to a focus. In this way, the heavy materials needed from Earth to build and power the habitat are largely limited to the solar concentrator and regolith moving and moulding equipment. By illuminating with a reflector rather than with electricity, the solar collection area is 20 times smaller than would be needed for PV cells. This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades'.