Mycobacterium tuberculosis infection induces non-apoptotic cell death of human dendritic cells

<p>Abstract</p> <p>Background</p> <p>Dendritic cells (DCs) connect innate and adaptive immunity, and are necessary for an efficient CD4⁺and CD8⁺T cell response after infection with <it>Mycobacterium tuberculosis </it>(Mtb). We previously described the macrophage cell death response to Mtb infection. To investigate the effect of Mtb infection on human DC viability, we infected these phagocytes with different strains of Mtb and assessed viability, as well as DNA fragmentation and caspase activity. In parallel studies, we assessed the impact of infection on DC maturation, cytokine production and bacillary survival.</p> <p>Results</p> <p>Infection of DCs with live Mtb (H37Ra or H37Rv) led to cell death. This cell death proceeded in a caspase-independent manner, and without nuclear fragmentation. In fact, substrate assays demonstrated that Mtb H37Ra-induced cell death progressed without the activation of the executioner caspases, 3/7. Although the death pathway was triggered after infection, the DCs successfully underwent maturation and produced a host-protective cytokine profile. Finally, dying infected DCs were permissive for Mtb H37Ra growth.</p> <p>Conclusions</p> <p>Human DCs undergo cell death after infection with live Mtb, in a manner that does not involve executioner caspases, and results in no mycobactericidal effect. Nonetheless, the DC maturation and cytokine profile observed suggests that the infected cells can still contribute to TB immunity.</p

Widespread Selection Across Coding and Noncoding DNA in the Pea Aphid Genome

Genome-wide patterns of diversity and selection are critical measures for understanding how evolution has shaped the genome. Yet, these population genomic estimates are available for only a limited number of model organisms. Here we focus on the population genomics of the pea aphid (Acyrthosiphon pisum). The pea aphid is an emerging model system that exhibits a range of intriguing biological traits not present in classic model systems. We performed low-coverage genome resequencing of 21 clonal pea aphid lines collected from alfalfa host plants in North America to characterize genome-wide patterns of diversity and selection. We observed an excess of low-frequency polymorphisms throughout coding and noncoding DNA, which we suggest is the result of a founding event and subsequent population expansion in North America. Most gene regions showed lower levels of Tajima’s D than synonymous sites, suggesting that the majority of the genome is not evolving neutrally but rather exhibits significant constraint. Furthermore, we used the pea aphid’s unique manner of X-chromosome inheritance to assign genomic scaffolds to either autosomes or the X chromosome. Comparing autosomal vs. X-linked sequence variation, we discovered that autosomal genes show an excess of low frequency variants indicating that purifying selection acts more efficiently on the X chromosome. Overall, our results provide a critical first step in characterizing the genetic diversity and evolutionary pressures on an aphid genome

Potential of VIIRS Time Series Data for Aiding the USDA Forest Service Early Warning System for Forest Health Threats: A Gypsy Moth Defoliation Case Study

The Healthy Forest Restoration Act of 2003 mandated that a national forest threat Early Warning System (EWS) be developed. The USFS (USDA Forest Service) is currently building this EWS. NASA is helping the USFS to integrate remotely sensed data into the EWS, including MODIS data for monitoring forest disturbance at broad regional scales. This RPC experiment assesses the potential of VIIRS (Visible/Infrared Imager/Radiometer Suite) and MODIS (Moderate Resolution Imaging Spectroradiometer) data for contribution to the EWS. In doing so, the RPC project employed multitemporal simulated VIIRS and MODIS data for detecting and monitoring forest defoliation from the non-native Eurasian gypsy moth (Lymantria despar). Gypsy moth is an invasive species threatening eastern U.S. hardwood forests. It is one of eight major forest insect threats listed in the Healthy Forest Restoration Act of 2003. This RPC experiment is relevant to several nationally important mapping applications, including carbon management, ecological forecasting, coastal management, and disaster managemen

Photoreceptor Inner Segment Morphology in Best Vitelliform Macular Dystrophy

PURPOSE To characterize outer retina structure in best vitelliform macular dystrophy (BVMD) and to determine the effect of macular lesions on overlying and adjacent photoreceptors. METHODS Five individuals with BVMD were followed prospectively with spectral domain optical coherence tomography and confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO). The AOSLO cone photoreceptor mosaic images were obtained within and around retinal lesions. Cone density was measured inside and outside lesions. In 2 subjects, densities were compared with published measurements acquired ∼2.5 years before. One subject was imaged 3 times over a 5-month period. RESULTS The AOSLO imaging demonstrated that photoreceptor morphology within BVMD retinal lesions was highly variable depending on the disease stage, with photoreceptor structure present even in advanced disease. The AOSLO imaging was repeatable even in severe disease over short-time and long-time intervals. Photoreceptor density was normal in retinal areas immediately adjacent to lesions and stable over ∼2.5 years. Mobile disk-like structures possibly representing subretinal macrophages were also observed. CONCLUSION Combined confocal and nonconfocal split-detector AOSLO imaging reveals substantial variability within clinical lesions in all stages of BVMD. Longitudinal cellular photoreceptor imaging could prove a powerful tool for understanding disease progression and monitoring emerging therapeutic treatment response in inherited degenerations such as BVMD

The Effects of Object Shape, Fidelity, Color, and Luminance on Depth Perception in Handheld Mobile Augmented Reality

Depth perception of objects can greatly affect a user's experience of an augmented reality (AR) application. Many AR applications require depth matching of real and virtual objects and have the possibility to be influenced by depth cues. Color and luminance are depth cues that have been traditionally studied in two-dimensional (2D) objects. However, there is little research investigating how the properties of three-dimensional (3D) virtual objects interact with color and luminance to affect depth perception, despite the substantial use of 3D objects in visual applications. In this paper, we present the results of a paired comparison experiment that investigates the effects of object shape, fidelity, color, and luminance on depth perception of 3D objects in handheld mobile AR. The results of our study indicate that bright colors are perceived as nearer than dark colors for a high-fidelity, simple 3D object, regardless of hue. Additionally, bright red is perceived as nearer than any other color. These effects were not observed for a low-fidelity version of the simple object or for a more-complex 3D object. High-fidelity objects had more perceptual differences than low-fidelity objects, indicating that fidelity interacts with color and luminance to affect depth perception. These findings reveal how the properties of 3D models influence the effects of color and luminance on depth perception in handheld mobile AR and can help developers select colors for their applications.Comment: 9 pages, In proceedings of IEEE International Symposium on Mixed and Augmented Reality (ISMAR) 202

Modeling of Commercial Turbofan Engine with Ice Crystal Ingestion; Follow-On

The occurrence of ice accretion within commercial high bypass aircraft turbine engines has been reported under certain atmospheric conditions. Engine anomalies have taken place at high altitudes that have been attributed to ice crystal ingestion, partially melting, and ice accretion on the compression system components. The result was degraded engine performance, and one or more of the following: loss of thrust control (roll back), compressor surge or stall, and flameout of the combustor. As ice crystals are ingested into the fan and low pressure compression system, the increase in air temperature causes a portion of the ice crystals to melt. It is hypothesized that this allows the ice-water mixture to cover the metal surfaces of the compressor stationary components which leads to ice accretion through evaporative cooling. Ice accretion causes a blockage which subsequently results in the deterioration in performance of the compressor and engine. The focus of this research is to apply an engine icing computational tool to simulate the flow through a turbofan engine and assess the risk of ice accretion. The tool is comprised of an engine system thermodynamic cycle code, a compressor flow analysis code, and an ice particle melt code that has the capability of determining the rate of sublimation, melting, and evaporation through the compressor flow path, without modeling the actual ice accretion. A commercial turbofan engine which has previously experienced icing events during operation in a high altitude ice crystal environment has been tested in the Propulsion Systems Laboratory (PSL) altitude test facility at NASA Glenn Research Center. The PSL has the capability to produce a continuous ice cloud which is ingested by the engine during operation over a range of altitude conditions. The PSL test results confirmed that there was ice accretion in the engine due to ice crystal ingestion, at the same simulated altitude operating conditions as experienced previously in flight. The computational tool was utilized to help guide a portion of the PSL testing, and was used to predict ice accretion could also occur at significantly lower altitudes. The predictions were qualitatively verified by subsequent testing of the engine in the PSL. In a previous study, analysis of select PSL test data points helped to calibrate the engine icing computational tool to assess the risk of ice accretion. This current study is a continuation of that data analysis effort. The study focused on tracking the variations in wet bulb temperature and ice particle melt ratio through the engine core flow path. The results from this study have identified trends, while also identifying gaps in understanding as to how the local wet bulb temperature and melt ratio affects the risk of ice accretion and subsequent engine behavior