Engulfment of apoptotic cells requires presentation of new cell surface ligands by the dying cells. Using a differential proteomics technology, we identify that annexin I is a caspase-dependent engulfment ligand; it is recruited from the cytosol and exported to the outer plasma membrane leaflet, colocalizes with phosphatidylserine, and is required for efficient clearance of apoptotic cells. Furthermore, phosphatidylserine receptor (PSR) clustering around apoptotic cells indicates a requirement for annexin I. In the nematode Caenorhabditis elegans, downregulation of the annexin homolog prevents efficient engulfment of pharyngeal cell corpses. These results provide novel mechanistic insights into how apoptotic cells are removed and may explain a pathogenic mechanism of chronic inflammatory diseases where annexin I autoantibodies have been described.

This work presents the first direct evidence of multivalent binding between bone morphogenetic protein-2 (BMP-2) and cartilage oligomeric matrix protein (COMP) using highresolution atomic force microscopy (AFM) imaging. AFM topographic images reveal the molecular morphology of COMP, a pentameric protein whose five identical monomer units bundle together at N-termini, extending out with flexible chains to C-termini. Upon addition of BMP-2, COMP molecules undergo conformational changes at the C-termini to enable binding with BMP-2 molecules. AFM enables local structural changes of COMP to be revealed upon binding various numbers, 1-5, of BMP-2 molecules. These BMP-2/COMP complexes exhibit very different morphologies from those of COMP: much more compact and thus less flexible. These molecular level insights deepen current understanding of the mechanism of how BMP-2/COMP complex enhances osteogenesis among osteoprogenitor cells: i.e., multivalent presentation of BMP-2 via the stable and relatively rigid BMP-2/COMP complex could form a lattice of interaction between multiple BMP-2 and BMP-2 receptors. These ligand-receptor clusters lead to fast initiation and sustained activation of the Smad signaling pathway, resulting in enhanced osteogenesis. This work is also of translational importance, as the outcome may enable usage of lower BMP-2 dosage for bone repair and regeneration.

Experimental measurements of the induction distances are given for hydrogen-oxygen, acetyleneoxygen, acetylene-air, methane-oxygen, carbon monoxide-oxygen, hydrogen-oxygen-nitrogen, hydrogen-oxygen-helium, hydrogen-oxygen-argon, and hydrogen-oxygen-carbon dioxide mixtures at initial pressures of 1, 5, 10 and 25 atm. An empirical relationship involving the combustion temperature, burning velocity, sonic velocity in the unburned gas and Reynolds number based on the burning velocity has been established to predict detonation induction distances of certain combustible gas mixtures. The correlation is not satisfactory for mixtures containing hydrocarbons; an explanation of this discrepancy is offered.

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