A Weak Neutralizing Antibody Response to Hepatitis C Virus Envelope Glycoprotein Enhances Virus Infection

We have completed a phase 1 safety and immunogenicity trial with hepatitis C virus (HCV) envelope glycoproteins, E1 and E2, with MF59 adjuvant as a candidate vaccine. Neutralizing activity to HCV genotype 1a was detected in approximately 25% of the vaccinee sera. In this study, we evaluated vaccinee sera from poor responders as a potential source of antibody dependent enhancement (ADE) of HCV infection. Sera with poor neutralizing activity enhanced cell culture grown HCV genotype 1a or 2a, and surrogate VSV/HCV pseudotype infection titer, in a dilution dependent manner. Surrogate pseudotypes generated from individual HCV glycoproteins suggested that antibody to the E2 glycoprotein; but not the E1 glycoprotein, was the principle target for enhancing infection. Antibody specific to FcRII expressed on the hepatic cell surface or to the Fc portion of Ig blocked enhancement of HCV infection by vaccinee sera. Together, the results from in vitro studies suggested that enhancement of viral infectivity may occur in the absence of a strong antibody response to HCV envelope glycoproteins

Proteomic Modeling for HIV-1 Infected Microglia-Astrocyte Crosstalk

Background: HIV-1-infected and immune competent brain mononuclear phagocytes (MP; macrophages and microglia) secrete cellular and viral toxins that affect neuronal damage during advanced disease. In contrast, astrocytes can affect disease by modulating the nervous system’s microenvironment. Interestingly, little is known how astrocytes communicate with MP to influence disease. Methods and Findings: MP-astrocyte crosstalk was investigated by a proteomic platform analysis using vesicular stomatitis virus pseudotyped HIV infected murine microglia. The microglial-astrocyte dialogue was significant and affected microglial cytoskeleton by modulation of cell death and migratory pathways. These were mediated, in part, through F-actin polymerization and filament formation. Astrocyte secretions attenuated HIV-1 infected microglia neurotoxicity and viral growth linked to the regulation of reactive oxygen species. Conclusions: These observations provide unique insights into glial crosstalk during disease by supporting astrocytemediated regulation of microglial function and its influence on the onset and progression of neuroAIDS. The results open new insights into previously undisclosed pathogenic mechanisms and open the potential for biomarker discovery an

The OSIRIS-REx Contamination Control and Witness Strategy

The OSIRIS-REx mission (Origins, Spectral Interpretation, Resource Identification, and Security Regolith Explorer) is the third NASA New Frontiers mission. It is scheduled for launch in 2016. The primary objective of the mission is to return at least 60 g of "pristine" material from the B-type near- Earth asteroid (101955) Bennu, which is spectrally similar to organic-rich CI or CM meteorites [1]. The study of these samples will advance our understanding of materials available for the origin of life on Earth or elsewhere. The spacecraft will rendezvous with Bennu in 2018 and spend at least a year characterizing the asteroid before executing a maneuver to recover a sample of regolith in the touch-and-go sample acquisition mechanism (TAGSAM). The TAGSAM and sample is stowed in the sample return capsule (SRC) and returned to Earth in 2023

The influence of anaesthetic agents on spiking and subthreshold activity in visual cortex revealed by electrophysiology and high-resolution functional MRI

The state of unconsciousness during anaesthesia is not characterized by a global disruption of CNS activity. Instead consciousness is mediated by a specific subset of brain states or processes selectively affected by anaesthetics. Our aim is to study the action sites of different types of anaesthetics in the monkey brain (M. mulatta). Here we report on the neural effects of Ketamine, a dissociative anaesthetic acting primarily on the NMDA receptor, and Midazolam, a benzodiazepine affecting GABA(A)-receptors. Ketamine exhibits both inhibitory and excitatory effects at different brain sites. Midazolam, however, is known to increase the GABA(A)-receptor function, and therefore to inhibit cortical activity. To study the primary sites-of-action of these agents in the monkey brain, high-resolution functional magnetic resonance imaging (fMRI) was used to measure stimulus induced activity changes in the alert and anaesthetized monkey. The activity of neurons in visual cortex was recorded during scanning, as well as in separate experiments outside the scanner. Following the acquisition of base-line data, a bolus of the test-substance was applied intravenously via a computerized infusion pump. Brain activity was monitored continuously before, during and after the infusion. The data presented here focus on the effects of anaesthetics on subthreshold and spiking activity and the BOLD-signal. A comparison of the influences on these different neural signals allows studying the site and type of action of anaesthetics in more detail. In addition it has the potential to afford further insights into the neural processes underlying the BOLD-signal