Host Immune Responses to a Viral Immune Modulating Protein: Immunogenicity of Viral Interleukin-10 in Rhesus Cytomegalovirus-Infected Rhesus Macaques

, consistent with a central role for rhcmvIL-10 during acute virus-host interactions. Since cmvIL-10 and rhcmvIL-10 are extremely divergent from the cIL-10 of their respective hosts, vaccine-mediated neutralization of their function could inhibit establishment of viral persistence without inhibition of cIL-10.As a prelude to evaluating cmvIL-10-based vaccines in humans, the rhesus macaque model of HCMV was used to interrogate peripheral and mucosal immune responses to rhcmvIL-10 in RhCMV-infected animals. ELISA were used to detect rhcmvIL-10-binding antibodies in plasma and saliva, and an IL-12-based bioassay was used to quantify plasma antibodies that neutralized rhcmvIL-10 function. rhcmvIL-10 is highly immunogenic during RhCMV infection, stimulating high avidity rhcmvIL-10-binding antibodies in the plasma of all infected animals. Most infected animals also exhibited plasma antibodies that partially neutralized rhcmvIL-10 function but did not cross-neutralize the function of rhesus cIL-10. Notably, minimally detectable rhcmvIL-10-binding antibodies were detected in saliva.This study demonstrates that rhcmvIL-10, as a surrogate for cmvIL-10, is a viable vaccine candidate because (1) it is highly immunogenic during natural RhCMV infection, and (2) neutralizing antibodies to rhcmvIL-10 do not cross-react with rhesus cIL-10. Exceedingly low rhcmvIL-10 antibodies in saliva further suggest that the oral mucosa, which is critical in RhCMV natural history, is associated with suboptimal anti-rhcmvIL-10 antibody responses

Phosphatidylserine targeting for diagnosis and treatment of human diseases

Cells are able to execute apoptosis by activating series of specific biochemical reactions. One of the most prominent characteristics of cell death is the externalization of phosphatidylserine (PS), which in healthy cells resides predominantly in the inner leaflet of the plasma membrane. These features have made PS-externalization a well-explored phenomenon to image cell death for diagnostic purposes. In addition, it was demonstrated that under certain conditions viable cells express PS at their surface such as endothelial cells of tumor blood vessels, stressed tumor cells and hypoxic cardiomyocytes. Hence, PS has become a potential target for therapeutic strategies aiming at Targeted Drug Delivery. In this review we highlight the biomarker PS and various PS-binding compounds that have been employed to target PS for diagnostic purposes. We emphasize the 35 kD human protein annexin A5, that has been developed as a Molecular Imaging agent to measure cell death in vitro, and non-invasively in vivo in animal models and in patients with cardiovascular diseases and cancer. Recently focus has shifted from diagnostic towards therapeutic applications employing annexin A5 in strategies to deliver drugs to cells that express PS at their surface

Optical Imaging of Bacterial Infections

The rise in multidrug resistant (MDR) bacteria has become a global crisis. Rapid and accurate diagnosis of infection will facilitate antibiotic stewardship and preserve our ability to treat and cure patients from bacterial infection. Direct in situ imaging of bacteria offers the prospect of accurately diagnosing disease and monitoring patient outcomes and response to treatment in real-time. There have been many recent advances in the field of optical imaging of infection; namely in specific probe and fluorophore design. This combined with the advances in imaging device technology render direct optical imaging of infection a feasible approach for accurate diagnosis in the clinic. Despite this, there are currently no licensed molecular probes for clinical optical imaging of infection. Here we report some of the most promising and interesting probes and approaches under development for this purpose, which have been evaluated in in vivo models within the laboratory setting

Technical memorandum ; #60

Abstract: Reconnaissance of Red Rock Valley was begun on December 10, 1953, and completed on February 11, 1954. The mines in the region were investigated and all exposures of Salt Wash were walked. Paleostream directions and alterations of the sandstones were observed and recorded on a base map. No important new mineralization was discovered-and the area is considered to be of no commercial significance if judged by the outcrops alone. However, a vast amount of Salt Wash lies at slight depth directly to the east of the investigated area

Integrated impact of tropical cyclones on sea surface chlorophyll in the North Atlantic

6 pages, 3 figures, 1 table.-- Supporting information http://onlinelibrary.wiley.com/doi/10.1029/2007GL031862/suppinfoPast studies have shown that surface chlorophyll-a concentrations increase in the wake of hurricanes. Given the reported increase in the intensity of North Atlantic hurricanes in recent years, increasing chlorophyll-a concentrations, perhaps an indication of increasing biological productivity, would be an expected consequence. However, in order to understand the impact of variable hurricane activity on ocean biology, the magnitude of the hurricane-induced chlorophyll increase relative to other events that stir or mix the upper ocean must be assessed. This study investigates the upper ocean biological response to tropical cyclones in the North Atlantic from 1997–2005. Specifically, we quantitatively compare the anomalous chlorophyll-a concentrations created by cyclone activity to the total distribution of anomalies in the subtropical waters. We show that the cyclone-induced chlorophyll-a increase has minimal impact on the integrated biomass budget, a result that holds even when taking into consideration the lagged and asymmetrical response of ocean colorThe authors gratefully acknowledge the SeaWiFS Project, NASA/Goddard Space Flight Center and support from the National Science FoundationPeer reviewe