NRP1 haploinsufficiency predisposes to the development of Tetralogy of Fallot.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. It involves anatomical abnormalities that change the normal flow of blood through the heart resulting in low oxygenation. Although not all of the underlying causes of TOF are completely understood, the disease has been associated with varying genetic etiologies including chromosomal abnormalities and Mendelian disorders, but can also occur as an isolated defect.

Membrane lipids and cell signaling.

Purpose Of Review: Reception and transmission of signals across the plasma membrane has been a function generally attributed to transmembrane proteins. In the last 3 years, however, a growing number of reports have further acknowledged important contributions played by membrane lipids in the process of signal transduction.

Recent Findings: In particular, the constituency of membrane lipids can regulate how proteins with SH2 domains and molecules like K-Ras expose their catalytic domains to the cytosol and interact with effectors and second messengers.

In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury.

The pathophysiological mechanism involved in side effects of radiation therapy, and especially the role of the endothelium remains unclear. Previous results showed that plasminogen activator inhibitor-type 1 (PAI-1) contributes to radiation-induced intestinal injury and suggested that this role could be driven by an endothelium-dependent mechanism. We investigated whether endothelial-specific PAI-1 deletion could affect radiation-induced intestinal injury.

ADAMTS1 interacts with, cleaves, and modifies the extracellular location of the matrix inhibitor tissue factor pathway inhibitor-2.

ADAMTS1 is an extracellular metalloproteinase known to participate in a variety of biological processes that includes inflammation, angiogenesis, and development of the urogenital system. Many of its functions rely on its catalytic activity, which thus far has been limited to the cleavage of the matrix proteoglycans aggrecan and versican. However, it is likely that other substrates exist.