Apoptotic cell-derived ICAM-3 promotes both macrophage chemoattraction to and tethering of apoptotic cells

A wide range of molecules acting as apoptotic cell-associated ligands, phagocyte-associated receptors or soluble bridging molecules have been implicated within the complex sequential processes that result in phagocytosis and degradation of apoptotic cells. Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance, although its precise role in the clearance process is ill defined. The main objective of this work is to further characterise the function of ICAM-3 in the removal of apoptotic cells. Using a range of novel anti-ICAM-3 monoclonal antibodies (mAbs), including one (MA4) that blocks apoptotic cell clearance by macrophages, alongside apoptotic human leukocytes that are normal or deficient for ICAM-3, we demonstrate that ICAM-3 promotes a domain 1–2-dependent tethering interaction with phagocytes. Furthermore, we demonstrate an apoptosis-associated reduction in ICAM-3 that results from release of ICAM-3 within microparticles that potently attract macrophages to apoptotic cells. Taken together, these data suggest that apoptotic cell-derived microparticles bearing ICAM-3 promote macrophage chemoattraction to sites of leukocyte cell death and that ICAM-3 mediates subsequent cell corpse tethering to macrophages. The defined function of ICAM-3 in these processes and profound defect in chemotaxis noted to ICAM-3-deficient microparticles suggest that ICAM-3 may be an important adhesion molecule involved in chemotaxis to apoptotic human leukocytes

Who Moved My E-Journal: Electronic Resources and Organizational Change

Tyler Walters is the Associate Director, Technology and Resource Services, Georgia Institute of Technology Library and Information Center, where he provides leadership, vision, and expertise for systems, digital initiatives, acquisitions, cataloging, and university archives and records units. Among his specific roles and initiatives at Georgia Tech are: leading activities to capture, preserve, disseminate, and promote the use of Georgia Tech’s digital intellectual output; defining standards, policies, and operations to organize metadata and systems for a variety of content forms; investigating integrating scholarly information systems into digital learning environments; coordinating Library involvement in national, regional, and state-level technology and resource management initiatives; facilitating the shift to electronic information resources--their licensing, technological management, and preservation. Robert H. McDonald is the Associate Director of Libraries for Technology & Research at Florida State University. He is responsible for the Division of Library Technology & Research which is comprised of the Digital Library Center, the Interactive Multimedia Center, the Library Technology Department, the Electronic Resources Management Department, and the Research and Development Group. Prior to his position at FSU, McDonald was the Information Technology and Digital Projects Librarian at Auburn University. Gregory Raschke is Interim Associate Director for Collection Management Organization & Preservation at North Carolina State University.The enigma of electronic resources has brought a tidal wave of change to the academy. Research Libraries are at a crossroads that will see their networked infrastructure become the primary means of management, retrieval, and access to all content while print access will take on a decidedly ancillary role that does not fall into this digital rubric. With this new paradigm research libraries must face the changes in personnel management, hiring/recruiting, skills acquisition and development, workflow design, teamwork and team formation, organizational structure, and impacts on organizational culture and internal communications that will be necessary to truly support a primary digital information environment. This panel will consist of three senior library leadership representatives from Florida State University, the Georgia Institute of Technology, and North Carolina State University who will discuss current trends and applied approaches to these issues within their libraries and will offer time for discussion with attendees on this important foundation for electronic resources management

Extensive Conformational Heterogeneity within Protein Cores

[Image: see text] Basic principles of statistical mechanics require that proteins sample an ensemble of conformations at any nonzero temperature. However, it is still common to treat the crystallographic structure of a protein as the structure of its native state, largely because high-resolution structural characterization of protein flexibility remains a profound challenge. To assess the typical degree of conformational heterogeneity within folded proteins, we construct Markov state models describing the thermodynamics and kinetics of proteins ranging from 72 to 263 residues in length. Each of these models is built from hundreds of microseconds of atomically detailed molecular dynamics simulations. Examination of the side-chain degrees of freedom reveals that almost every residue visits at least two rotameric states over this time frame, with rotamer transition rates spanning a wide range of time scales (from nanoseconds to tens of microseconds). We also report substantial backbone dynamics on time scales longer than are typically addressed by experimental measures of protein flexibility, such as NMR order parameters. Finally, we demonstrate that these extensive rearrangements are consistent with NMR and crystallographic data, which supports the validity of our models. Altogether, these results depict the interior of proteins not as well-ordered solids, as is often imagined, but instead as dense fluids, which undergo substantial structural fluctuations despite their high packing fraction