p16 a biomarker of aging and tolerance for cancer therapy.

There is great variability in life-expectancy, physical, cognitive, and functional domains in cancer patients of similar chronologic age. Nowhere is this more apparent than among middle-aged and older patients. However, even in younger patients of similar age, extensive exposure to environmental stressors can cause great variability in health status.

The Ras activator RasGRP3 mediates diabetes-induced embryonic defects and affects endothelial cell migration.

Rationale: Fetuses that develop in diabetic mothers have a higher incidence of birth defects that include cardiovascular defects, but the signaling pathways that mediate these developmental effects are poorly understood. It is reasonable to hypothesize that diabetic maternal effects are mediated by 1 or more pathways activated downstream of aberrant glucose metabolism, because poorly controlled maternal glucose levels correlate with the frequency and severity of the defects.

Objective: We investigated whether RasGRP3 (Ras guanyl-releasing protein 3), a Ras activator expressed in developing blood vessels, mediates diabetes-induced vascular developmental defects.

In vitro differentiation of mouse embryonic stem cells into primitive blood vessels.

Mouse embryonic stem (ES) cells, derived from the inner cell mass of blastocyst stage embryos, undergo programmed differentiation in vitro to form a primitive vasculature. This programmed differentiation proceeds through similar processes of vasculogenesis and angiogenesis found during early vascular development in vivo. Partially differentiated ES cell clumps or embryoid bodies (EBs) first form blood islands that are subsequently transformed into a network of primitive blood vessels that contain lumens.

Peptide rescues GLUT4 recruitment, but not GLUT4 activation, in insulin resistance.

Insulin-stimulated GLUT4 recruitment to the plasma membrane is impaired in insulin resistance. We recently reported that a cell permeable phosphoinositide-binding peptide induces GLUT4 recruitment as potently as insulin, but does not activate GLUT4 to initiate glucose uptake. Here we investigated whether the peptide-induced GLUT4 recruitment is intact in insulin resistance.

Purification of salmon thrombin and its potential as an alternative to mammalian thrombins in fibrin sealants.

A method to produce highly purified thrombin from salmon blood is described, and a series of biochemical, cell biologic, and biophysical assays demonstrate the functional similarities and some differences between salmon and human thrombins. Salmon thrombin with specific activity greater than 1000 units/mg total protein can be prepared by modifications of the methods used for purification of human thrombin. Using a synthetic substrate based on the human fibrinogen A-alpha polypeptide sequence as an indicator of enzymatic activity, salmon and human thrombin preparations contain similar specific activities per mass of purified protein.