Astrocytes play a key role in activation of microglia by persistent Borna disease virus infection

Neonatal Borna disease virus (BDV) infection of the rat brain is associated with microglial activation and damage to certain neuronal populations. Since persistent BDV infection of neurons is nonlytic in vitro, activated microglia have been suggested to be responsible for neuronal cell death in vivo. However, the mechanisms of activation of microglia in neonatally BDV-infected rat brains remain unclear. Our previous studies have shown that activation of microglia by BDV in culture requires the presence of astrocytes as neither the virus nor BDV-infected neurons alone activate microglia. Here, we evaluated the mechanisms whereby astrocytes can contribute to activation of microglia in neuron-glia-microglia mixed cultures. We found that persistent infection of neuronal cells leads to activation of uninfected astrocytes as measured by elevated expression of RANTES. Activation of astrocytes then produces activation of microglia as evidenced by increased formation of round-shaped, MHCI-, MHCII- and IL-6-positive microglia cells. Our analysis of possible molecular mechanisms of activation of astrocytes and/or microglia in culture indicates that the mediators of activation may be soluble heat-resistant, low molecular weight factors. The findings indicate that astrocytes may mediate activation of microglia by BDV-infected neurons. The data are consistent with the hypothesis that microglia activation in the absence of neuronal damage may represent initial steps in the gradual neurodegeneration observed in brains of neonatally BDV-infected rats

Changes in mumps virus neurovirulence phenotype associated with quasispecies heterogeneity

AbstractMumps virus is a highly neurotropic virus with evidence of central nervous system invasion (CNS) in approximately half of all cases of infection. In countries where live attenuated mumps virus vaccines were introduced, the number of mumps cases declined dramatically; however, recently, the safety of some vaccine strains has been questioned. For example, one of the most widely used vaccines, the Urabe AM9 strain, was causally associated with meningitis, leading to the withdrawal of this product from the market in several countries. This highlights the need for a better understanding of the attenuation process and the identification of markers of attenuation. To this end, we further attenuated the Urabe AM9 strain by serial passage in cell culture and compared the complete nucleotide sequences of the parental and passaged viruses. Interestingly, despite a dramatic decrease in virus virulence (as assayed in rats), the only genomic changes were in the form of changes in the level of genetic heterogeneity at specific genome sites, i.e., either selection of one nucleotide variant at positions where the starting material exhibited nucleotide heterogeneity or the evolution of an additional nucleotide to create a heterogenic site. This finding suggests that changes in the level of genetic heterogeneity at specific genome sites can have profound neurovirulence phenotypic consequences and, therefore, caution should be exercised when evaluating genetic markers of virulence or attenuation based only on a consensus sequence

SDHA gain-of-function engages inflammatory mitochondrial retrograde signaling via KEAP1-Nrf2.

Whether screening the metabolic activity of immune cells facilitates discovery of molecular pathology remains unknown. Here we prospectively screened the extracellular acidification rate as a measure of glycolysis and the oxygen consumption rate as a measure of mitochondrial respiration in B cells from patients with primary antibody deficiency. The highest oxygen consumption rate values were detected in three study participants with persistent polyclonal B cell lymphocytosis (PPBL). Exome sequencing identified germline mutations in SDHA, which encodes succinate dehydrogenase subunit A, in all three patients with PPBL. SDHA gain-of-function led to an accumulation of fumarate in PPBL B cells, which engaged the KEAP1-Nrf2 system to drive the transcription of genes encoding inflammatory cytokines. In a single patient trial, blocking the activity of the cytokine interleukin-6 in vivo prevented systemic inflammation and ameliorated clinical disease. Overall, our study has identified pathological mitochondrial retrograde signaling as a disease modifier in primary antibody deficiency

New lidar systems at the German Aerospace Center

This work gives an overview of the lower-, middle and upper atmosphere lidar projects at the German Aerospace Center (DLR). The Temperature Lidar for Middle Atmosphere research (TELMA) is a combined sodium/Rayleigh/Brillouin-lidar integrated into an 8-foot container. It will provide temperature profiles with high temporal and spatial resolution from near ground level up to approximately 110 km altitude. The lidar system is designed for remote/autonomous operation. First observations with the Rayleigh-lidar were carried out during the DEEPWAVE campaign in New Zealand in 2014. The CORAL (Compact Rayleigh Autonomous Lidar) instrument is derived from an upgraded version of the Rayleigh-lidar originally developed for the TELMA project. It is also integrated into an 8-foot container and features an improved software package for autonomous operation. Making use of extensive self-monitoring and fault protection algorithms, no human intervention is needed to initiate start-up of the lidar, monitoring of system parameters, or shutdown of the lidar. These capabilities make CORAL the first instrument of a new class of truly automatic mesospheric lidar systems. CORAL and TELMA serve as prototypes and technology testbeds for ALIMA, the Airborne Lidar for studying the Middle Atmosphere. ALIMA makes use of a novel laser to generate the large output power required for very high resolution measurements of temperature, vertical wind and iron density at 372 nm wavelength. The lidar system will be able to resolve horizontal wavelengths down to 10 km during flight. Used as ground-based instrument, ALIMA will enable momentum flux measurements with unprecedented precision. First flight of ALIMA on the DLR Falcon aircraft is planned for 2017

Injection seeded ns-pulsed Nd:YAG laser at 1116 nm for Fe-Lidar

Vorstellung eines injection-seeded Nd:YAG Laser bei 1116 nm für Eisen-Lida

Demonstration of an iron fluorescence lidar operating at 372 nm wavelength using a newly-developed Nd:YAG laser

We report on the development of a pulsed neodymium-doped yttrium aluminum garnet (Nd:YAG) laser operating at a 1116 nm wavelength. Because the third harmonic is within a few gigahertz of the 372 nm absorption line of iron, this laser system represents an alternative to alexandrite lasers commonly used in iron fluorescence lidars. With our prototype, we achieved a 0.5 W at 372 nm wavelength and a 100 Hz pulse repetition frequency. As a proof of concept, we show iron density measurements, which have been acquired using the novel lidar transmitter