Tracer Survey in the Cape Verde Region Traceraufnahme in der Kapverdenregion Cruise No. 10, Leg 1 October 31 – December 06, 2008 Ponta Delgada (Portugal) – Mindelo (Cape Verde Islands)

The research cruise MSM10/1 was extremely successful. All programs were able to collect high quality data and the anticipated goals of the expedition were fully met. We have been able to carry out the first comprehensive survey of a tracer release in the Guinea Upwelling region (GUTRE) roughly seven month after the tracer was released at 8°N 23°W in April 2008. We have estimated that a total of 40% of the tracer was found during this cruise. While the horizontal spreading and mixing was larger than anticipated, the vertical extent of the tracer found was small. The low vertical tracer spreading rate estimates are supported by the micro structure profile data. The extensive survey of the upper 1000m of the oxygen minimum zone (OMZ) allowed comparing our sections with several previous surveys. We found that the lowest oxygen values in the core of the OMZ have dropped at record low values below 40 μmol/kg. The preliminary findings from the trace metal work focused on Fe ligand measurements shows a slight higher excess ligand concentration in the surface (50m) for three stations. The two other stations show a slight decrease at this depth. A large number of biochemical samples were taken and were analyzed in Kiel for DNA and RNA diversity. The tracer release experiment provided an ideal environment for repeated biochemical sampling in the same water mass

Pentavalent Sialic Acid Conjugates Block Coxsackievirus A24 Variant and Human Adenovirus Type 37–Viruses That Cause Highly Contagious Eye Infections

Coxsackievirus A24 variant (CVA24v) and human adenovirus 37 (HAdV-37) are leading causative agents of the severe and highly contagious ocular infections acute hemorrhagic conjunctivitis and epidemic keratoconjunctivitis, respectively. Currently, neither vaccines nor antiviral agents are available for treating these diseases, which affect millions of individuals worldwide. CVA24v and HAdV-37 utilize sialic acid as attachment receptors facilitating entry into host cells. Previously, we and others have shown that derivatives based on sialic acid are effective in preventing HAdV-37 binding and infection of cells. Here, we designed and synthesized novel pentavalent sialic acid conjugates and studied their inhibitory effect against CVA24v and HAdV-37 binding and infection of human corneal epithelial cells. The pentavalent conjugates are the first reported inhibitors of CVA24v infection and proved efficient in blocking HAdV-37 binding. Taken together, the pentavalent conjugates presented here form a basis for the development of general inhibitors of these highly contagious ocular pathogens

Structure of the Extracellular Portion of CD46 Provides Insights into Its Interactions with Complement Proteins and Pathogens

The human membrane cofactor protein (MCP, CD46) is a central component of the innate immune system. CD46 protects autologous cells from complement attack by binding to complement proteins C3b and C4b and serving as a cofactor for their cleavage. Recent data show that CD46 also plays a role in mediating acquired immune responses, and in triggering autophagy. In addition to these physiologic functions, a significant number of pathogens, including select adenoviruses, measles virus, human herpes virus 6 (HHV-6), Streptococci, and Neisseria, use CD46 as a cell attachment receptor. We have determined the crystal structure of the extracellular region of CD46 in complex with the human adenovirus type 11 fiber knob. Extracellular CD46 comprises four short consensus repeats (SCR1-SCR4) that form an elongated structure resembling a hockey stick, with a long shaft and a short blade. Domains SCR1, SCR2 and SCR3 are arranged in a nearly linear fashion. Unexpectedly, however, the structure reveals a profound bend between domains SCR3 and SCR4, which has implications for the interactions with ligands as well as the orientation of the protein at the cell surface. This bend can be attributed to an insertion of five hydrophobic residues in a SCR3 surface loop. Residues in this loop have been implicated in interactions with complement, indicating that the bend participates in binding to C3b and C4b. The structure provides an accurate framework for mapping all known ligand binding sites onto the surface of CD46, thereby advancing an understanding of how CD46 acts as a receptor for pathogens and physiologic ligands of the immune system