The emergence of Zika virus (ZIKV) as a global health threat has highlighted the unmet need for ZIKV-specific vaccines and antiviral treatments. ZIKV infects dendritic cells (DC), which have pivotal functions in activating innate and adaptive antiviral responses; however, the mechanisms by which DC function is subverted to establish ZIKV infection are unclear. Here we develop a genomics profiling method that enables discrete analysis of ZIKV-infected versus neighboring, uninfected primary human DCs to increase the sensitivity and specificity with which ZIKV-modulated pathways can be identified. The results show that ZIKV infection specifically increases the expression of genes enriched for lipid metabolism-related functions. ZIKV infection also increases the recruitment of sterol regulatory element-binding protein (SREBP) transcription factors to lipid gene promoters, while pharmacologic inhibition or genetic silencing of SREBP2 suppresses ZIKV infection of DCs. Our data thus identify SREBP2-activated transcription as a mechanism for promoting ZIKV infection amenable to therapeutic targeting.
The United States energy industry is transforming with the rapid development of alternative energy sources and technological advancements in fossil fuels. Two major changes include the growth of wind turbines and unconventional oil and gas. We measured land-use impacts and associated ecosystem services costs of unconventional gas and wind energy development within the Anadarko Basin of the Oklahoma Woodford Shale, an area that has experienced large increases in both energy sectors. Unconventional gas wells developed three times as much land compared to wind turbines (on a per unit basis), resulting in higher ecosystem services costs for gas. Gas wells had higher impacts on intensive agricultural lands (i.e., row crops) compared to wind turbines that had higher impacts on natural grasslands/pastures. Because wind turbines produced on average less energy compared to gas wells, the average land-use-related ecosystem cost per gigajoule of energy produced was almost the same. Our results demonstrate that both unconventional gas and wind energy have substantial impacts on land use, which likely affect wildlife populations and land-use-related ecosystem services. Although wind energy does not have the associated greenhouse gas emissions, we suggest that the direct impacts on ecosystems in terms of land use are similar to unconventional fossil fuels. Considering the expected rapid global expansion of these two forms of energy production, many ecosystems are likely to be at risk.
Tissue ablation with pulses in the femtosecond regime is generally more efficient and causes less collateral and thermal damage to the surrounding tissue compared to ablation with longer pulsewidths. A compact, flexible fiber delivery system that could transmit these pulses would be advantageous over free-space beam delivery, since it would allow ultrashort pulse tissue ablation in vivo. However, the extremely high intensities associated with ultrashort pulses have deleterious effects in conventional silica fibers such as nonlinearities and fiber damage. Hollow silica waveguides with a silver inner coating essentially guide the pulses in air, thereby avoiding many of these problems. The transmission characteristics of four hollow waveguides with bore diameters of 300, 500, 750 and 1000µm and lengths up to 1m were tested using pulses from a femtosecond regime Ti:Sapphire laser operating with input pulses <150fs duration and energy up to 700 microjoules at a repetition rate of 1kHz. Coupling was primarily to the HE 11 mode and straight and bending losses were measured. Beam profiles were also taken at the output of straight and bent waveguides. Autocorrelation measurements show minimal pulse broadening for straight waveguides and increasing pulsewidth with waveguide bend. Diffractive micro-optics were used to focus the output and ablation of fresh cadaveric porcine liver and heart tissues was accomplished using an x-y-z translational stage moving at 1 mm/second. Targeted tissues were then processed for light and electron microscopic examination. Light and scanning electron microscopy demonstrated near a-thermal ablation with depth correlating to energy application.
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