Comparison of definitions of early knee osteoarthritis for likelihood of progression at 2-year and 5-year follow-up: the Multicenter Osteoarthritis Study.

Background: Preventing worsening osteoarthritis (OA) in persons with early OA is a major treatment goal. We evaluated if different early OA definitions yielded enough cases of worsening OA within 2-5 years to make trial testing treatments feasible.

Methods: We assessed different definitions of early OA using data from Multicenter Osteoarthritis (MOST) Study participants who were followed up longitudinally.

The mechanism of pore formation by bacterial toxins.

A remarkable group of proteins challenge the notions that protein sequence determines a unique three-dimensional structure, and that membrane and soluble proteins are very distinct. The pore-forming toxins typically transform from soluble, monomeric proteins to oligomers that form transmembrane channels. Recent structural studies provide ideas about how these changes take place.

Structural basis of pore formation by the bacterial toxin pneumolysin.

The bacterial toxin pneumolysin is released as a soluble monomer that kills target cells by assembling into large oligomeric rings and forming pores in cholesterol-containing membranes. Using cryo-EM and image processing, we have determined the structures of membrane-surface bound (prepore) and inserted-pore oligomer forms, providing a direct observation of the conformational transition into the pore form of a cholesterol-dependent cytolysin. In the pore structure, the domains of the monomer separate and double over into an arch, forming a wall sealing the bilayer around the pore.

Structure-function analysis of human [corrected] phosphatidylinositol transfer protein alpha bound to phosphatidylinositol.

Phosphatidylinositol transfer protein alpha (PITPalpha) selectively transports and promotes exchange of phosphatidylinositol (PI) and phosphatidylcholine (PC) between lipid bilayers. In higher eukaryotes PITPalpha is required for cellular functions such as phospholipase C-mediated signaling, regulated exocytosis, and secretory vesicle formation. We have determined the crystal structure of human PITPalpha bound to its physiological ligand, PI, at 2.