RNA interference screening reveals host CaMK4 as a regulator of cryptococcal uptake and pathogenesis

ABSTRACT Cryptococcus neoformans , the causative agent of cryptococcosis, is an opportunistic fungal pathogen that kills over 200,000 individuals annually. This yeast may grow freely in body fluids, but it also flourishes within host cells. Despite extensive research on cryptococcal pathogenesis, host genes involved in the initial engulfment of fungi and subsequent stages of infection are woefully understudied. To address this issue, we combined short interfering RNA silencing and a high-throughput imaging assay to identify host regulators that specifically influence cryptococcal uptake. Of 868 phosphatase and kinase genes assayed, we discovered 79 whose silencing significantly affected cryptococcal engulfment. For 25 of these, the effects were fungus specific, as opposed to general alterations in phagocytosis. Four members of this group significantly and specifically altered cryptococcal uptake; one of them encoded CaMK4, a calcium/calmodulin-dependent protein kinase. Pharmacological inhibition of CaMK4 recapitulated the observed defects in phagocytosis. Furthermore, mice deficient in CaMK4 showed increased survival compared to wild-type mice upon infection with C. neoformans . This increase in survival correlated with decreased expression of pattern recognition receptors on host phagocytes known to recognize C. neoformans . Altogether, we have identified a kinase that is involved in C. neoformans internalization by host cells and in host resistance to this deadly infection. </jats:p

Influence of summer and winter climate variability on nitrogen wet deposition in Norway

Dominating wind patterns around Norway may change due to climate warming. This could affect transport of polluted air masses and precipitation. Here, we study relations between reactive nitrogen wet deposition and air mass transport during summer and winter expressed in the form of climate indices, at seven sites in Southern Norway for the period 1980&amp;ndash;2005. Atmospheric nitrate concentrations decreased with 0 to 50% in the period, particularly at sites with little precipitation, and mostly during 1990&amp;ndash;2005. For comparison, reported reductions in emissions of oxidised nitrogen in Europe in 1989&amp;ndash;2003 were 23%. Climate indices explained up to 36% of the variation in winter nitrate deposition at the western and northern sites &amp;ndash; and also explained 60% of the variation in winter precipitation (R=0.77). This suggests that the variation in nitrate wet deposition is closely related to variation in precipitation, and that the climate indices seem to also partly control the variation in atmospheric nitrate concentrations (R=&amp;minus;0.45 at coastal sites). At the coastal sites, local air temperature was highly correlated (R=0.84) with winter nitrate deposition, suggesting that warm, humid winter weather results in increased wet nitrate deposition. For ammonia the pattern was similar, but this compound is more influenced by local sources. Expected severe increase in precipitation in western and northern regions as a consequence of climate change suggest that nitrogen deposition in these areas will increase under global warming if emissions are held constant

Global Alfven Eigenmodes in the H-1 heliac

Recent upgrades in H-1 power supplies have enabled the operation of the H-1 experiment at higher heating powers than previously attainable. A heating power scan in mixed hydrogen/helium plasmas reveals a change in mode activity with increasing heating power. At low power (<50 kW) modes with beta-induced Alfven eigenmode (BAE) frequency scaling are observed. At higher power modes consistent with an analysis of nonconventional Global Alfven Eigenmodes (GAEs) are observed, the subject of this work. We have computed the mode continuum, and identified GAE structures using the ideal MHD solver CKA and the gyrokinetic code EUTERPE. An analytic model for ICRH-heated minority ions is used to estimate the fast ion temperature from the hydrogen species. Linear growth rate scans using a local flux surface stability calculation, LGRO, are performed. These studies demonstrate growth from circulating particles whose speed is significantly less than the Alfven speed, and are resonant with the mode through harmonics of the Fourier decomposition of the strongly-shaped heliac magnetic field. They reveal drive is possible with a small, hot energetic tail of the hydrogen species. Local linear growth rate scans are also complemented with global calculations from CKA and EUTERPE. These qualitatively confirm the findings from the LGRO study, and show that the inclusion of finite Larmor radius effects can reduce the growth rate by a factor of three, but do not affect marginal stability. Finally, a study of damping of the global mode with the thermal plasma is conducted, computing continuum, and the damping arising from parallel electric fields. We find that continuum damping is of order 0.1% for the configuration studied. The inclusion of resistivity lifts the damping to 19%. Such large damping is consistent with experimental observations that in absence of drive the mode decays rapidly (~0.1 ms).Comment: 18 pages, 15 figures, submitted 07/04/2017 to Plasma Physics and Controlled Fusio

Usefulness of high resolution coastal models for operational oil spill forecast: the "Full City" accident

Oil spill modeling is considered to be an important part of a decision support system (DeSS) for oil spill combatment and is useful for remedial action in case of accidents, as well as for designing the environmental monitoring system that is frequently set up after major accidents. Many accidents take place in coastal areas, implying that low resolution basin scale ocean models are of limited use for predicting the trajectories of an oil spill. In this study, we target the oil spill in connection with the "Full City" accident on the Norwegian south coast and compare operational simulations from three different oil spill models for the area. The result of the analysis is that all models do a satisfactory job. The "standard" operational model for the area is shown to have severe flaws, but by applying ocean forcing data of higher resolution (1.5 km resolution), the model system shows results that compare well with observations. The study also shows that an ensemble of results from the three different models is useful when predicting/analyzing oil spill in coastal areas

Climate Change: Helping Nature Survive the Human Response

Climate change poses profound, direct, and well-documented threats to biodiversity. A significant fraction of Earth’s species is at risk of extinction due to changing precipitation and temperature regimes, rising and acidifying oceans, and other factors. There is also growing awareness of the diversity and magnitude of responses, both proactive and reactive, that people will undertake as lives and livelihoods are affected by climate change. Yet to date few studies have examined the relationship between these two powerful forces. The natural systems upon which people depend, already under direct assault from climate change, are further threatened by how we respond to climate change. Human history and recent studies suggest that our actions to cope with climate change (adaptation) or lessen its rate and magnitude (mitigation) could have impacts that match—and even exceed—the direct effects of climate change on ecosystems. If we are to successfully conserve biodiversity and maintain ecosystem services in a warming world, considerable effort is needed to predict and reduce the indirect risks created by climate change

A Coordinated X-ray and Optical Campaign of the Nearby Massive Binary δ\delta Orionis Aa: II. X-ray Variability

We present time-resolved and phase-resolved variability studies of an extensive X-ray high-resolution spectral dataset of the $\delta$ Orionis Aa binary system. The four observations, obtained with Chandra ACIS HETGS, have a total exposure time of ~479 ks and provide nearly complete binary phase coverage. Variability of the total X-ray flux in the range 5-25 $\AA$ is confirmed, with maximum amplitude of about +/-15% within a single ~125 ks observation. Periods of 4.76d and 2.04d are found in the total X-ray flux, as well as an apparent overall increase in flux level throughout the 9-day observational campaign. Using 40 ks contiguous spectra derived from the original observations, we investigate variability of emission line parameters and ratios. Several emission lines are shown to be variable, including S XV, Si XIII, and Ne IX. For the first time, variations of the X-ray emission line widths as a function of the binary phase are found in a binary system, with the smallest widths at phase=0.0 when the secondary $\delta$ Orionis Aa2 is at inferior conjunction. Using 3D hydrodynamic modeling of the interacting winds, we relate the emission line width variability to the presence of a wind cavity created by a wind-wind collision, which is effectively void of embedded wind shocks and is carved out of the X-ray-producing primary wind, thus producing phase-locked X-ray variability.Comment: 36 pages, 14 Tables, 19 Figures, accepted by ApJ, one of 4 related papers to be published togethe

Climate change: Helping nature survive the human response

Climate change poses profound, direct, and well-documented threats to biodiversity. A significant fraction of Earth\u27s species is at risk of extinction due to changing precipitation and temperature regimes, rising and acidifying oceans, and other factors. There is also growing awareness of the diversity and magnitude of responses, both proactive and reactive, that people will undertake as lives and livelihoods are affected by climate change. Yet to date few studies have examined the relationship between these two powerful forces. The natural systems upon which people depend, already under direct assault from climate change, are further threatened by how we respond to climate change. Human history and recent studies suggest that our actions to cope with climate change (adaptation) or lessen its rate and magnitude (mitigation) could have impacts that match-and even exceed-the direct effects of climate change on ecosystems. If we are to successfully conserve biodiversity and maintain ecosystem services in a warming world, considerable effort is needed to predict and reduce the indirect risks created by climate change. ©2010 Wiley Periodicals, Inc.

ELM Characteristics in MAST

Edge localized mode (ELM) characteristics in a large spherical tokamak (ST) with significant auxiliary heating are explored. High confinement is achieved in mega ampere spherical tokamak (MAST) at low ELM frequencies even though the ELMs exhibit many type III characteristics. These ELMs are associated with a reduction in the pedestal density but no significant change in the pedestal temperature or temperature profile, indicating that energy is convected from the pedestal region into the scrape-off layer. Power to the targets during an ELM arrives predominantly at the low field outboard side. ELM effluxes are observed up to 20 cm from the plasma edge at the outboard mid-plane and are associated with the radial motion of a feature at an average velocity of 0.75 km s-1. The target balance observed in MAST is potentially rather favourable for the ST since H-mode access is facilitated in a regime where ELM losses flow mostly to the large wetted area, outboard targets and, in addition, the target heat loads are reduced by an even distribution of power between the upper and lower targets