Mosquitoes Inoculate High Doses of West Nile Virus as They Probe and Feed on Live Hosts

West Nile virus (WNV) is transmitted to vertebrate hosts by mosquitoes as they take a blood meal. The amount of WNV inoculated by mosquitoes as they feed on a live host is not known. Previous estimates of the amount of WNV inoculated by mosquitoes (101.2–104.3 PFU) were based on in vitro assays that do not allow mosquitoes to probe or feed naturally. Here, we developed an in vivo assay to determine the amount of WNV inoculated by mosquitoes as they probe and feed on peripheral tissues of a mouse or chick. Using our assay, we recovered approximately one-third of a known amount of virus inoculated into mouse tissues. Accounting for unrecovered virus, mean and median doses of WNV inoculated by four mosquito species were 104.3 PFU and 105.0 PFU for Culex tarsalis, 105.9 PFU and 106.1 PFU for Cx. pipiens, 104.7 PFU and 104.7 PFU for Aedes japonicus, and 103.6 PFU and 103.4 PFU for Ae. triseriatus. In a direct comparison, in vivo estimates of the viral dose inoculated by Cx. tarsalis were approximately 600 times greater than estimates obtained by an in vitro capillary tube transmission assay. Virus did not disperse rapidly, as >99% of the virus was recovered from the section fed or probed upon by the mosquito. Furthermore, 76% (22/29) of mosquitoes inoculated a small amount of virus (∼102 PFU) directly into the blood while feeding. Direct introduction of virus into the blood may alter viral tropism, lead to earlier development of viremia, and cause low rates of infection in co-feeding mosquitoes. Our data demonstrate that mosquitoes inoculate high doses of WNV extravascularly and low doses intravascularly while probing and feeding on a live host. Accurate estimates of the viral dose inoculated by mosquitoes are critical in order to administer appropriate inoculation doses to animals in vaccine, host competence, and pathogenesis studies

Joint M3 and Diviner Analysis of the Mineralogy, Glass Composition, and Country Rock Content of Pyroclastic Deposits in Oppenheimer Crater

Here we present our analysis of the near- and mid-infrared spectral properties of pyroclastic deposits within the floor fractured Oppenheimer Crater that are hypothesized to be Vulcanian in origin. These are the first results of our global study of lunar pyroclastic deposits aimed at constraining the range of eruption processes on the Moon. In the near-infrared, we have employed a new method of spectral analysis developed in Horgan et al. (2013) of the 1 m iron absorption band in Chandrayaan-1 Moon Mineralogy Mapper (M3) spectra. By analyzing both the position and shape of the 1 m band we can detect and map the distribution of minerals, glasses, and mixtures of these phases in pyroclastic deposits. We are also using mid-infrared spectra from the Lunar Reconnaissance Orbiter Diviner Lunar Radiometer Experiment to develop ~200 m/pixel Christiansen Feature (CF) maps, which correlate with silica abundance. One of the benefits of using CF maps for analysis of pyroclastic deposits is that they can be used to detect silicic country rock that may have been emplaced by Vulcanian-style eruptions, and are sensitive to iron abundance in glasses, neither of which is possible in the near-infrared. M3 analysis reveals that the primary spectral endmembers are low-calcium pyroxene and iron-bearing glass, with only minor high-calcium pyroxene, and no detectable olivine. The large deposit in the south shows higher and more extensive glass concentrations than the surrounding deposits. We interpret the M3 spectra of the pyroclastic deposits as indicating a mixture of low-calcium pyroxene country rock and juvenile glass, and no significant olivine. Analysis of Diviner CF maps of the Oppenheimer crater floor indicates an average CF value of 8.16, consistent with a mixture of primarily plagioclase and some pyroxene. The average CF values of the pyroclastic deposits range from 8.31 in the SW to 8.24 in the SE. Since CF values within the deposits are as high as 8.49, the lower average CF values of the deposits suggest that each deposit is a mixture of crater floor material and highly mafic juvenile material consistent with either olivine or Fe-bearing pyroclastic glass. Synthesizing our M3 and Diviner results indicates that the crater floor consists of plagioclase with some pyroxene, and the pyroclastic deposits are a mix of this substrate and a glass-rich juvenile material. While we cannot determine the iron content of the glass from M3 spectra alone, the high Diviner CF values suggest that the glass is relatively iron-rich. Indeed, FeO abundances inferred from CF values using the method of Allen et al. (2012) imply that the large southern deposit exhibits a significant enhancement in iron content. This supports our hypothesis that the glass in this deposit is relatively iron-rich

Habitable Climates: The Influence of Eccentricity

In the outer regions of the habitable zone, the risk of transitioning into a globally frozen "snowball" state poses a threat to the habitability of planets with the capacity to host water-based life. We use a one-dimensional energy balance climate model (EBM) to examine how obliquity, spin rate, orbital eccentricity, and ocean coverage might influence the onset of such a snowball state. For an exoplanet, these parameters may be strikingly different from the values observed for Earth. Since, for constant semimajor axis, the annual mean stellar irradiation scales with (1-e^2)^(-1/2), one might expect the greatest habitable semimajor axis (for fixed atmospheric composition) to scale as (1-e^2)^(-1/4). We find that this standard ansatz provides a reasonable lower bound on the outer boundary of the habitable zone, but the influence of obliquity and ocean fraction can be profound in the context of planets on eccentric orbits. For planets with eccentricity 0.5, our EBM suggests that the greatest habitable semimajor axis can vary by more than 0.8 AU (78%!) depending on obliquity, with higher obliquity worlds generally more stable against snowball transitions. One might also expect that the long winter at an eccentric planet's apoastron would render it more susceptible to global freezing. Our models suggest that this is not a significant risk for Earth-like planets around Sun-like stars since such planets are buffered by the thermal inertia provided by oceans covering at least 10% of their surface. Since planets on eccentric orbits spend much of their year particularly far from the star, such worlds might turn out to be especially good targets for direct observations with missions such as TPF-Darwin. Nevertheless, the extreme temperature variations achieved on highly eccentric exo-Earths raise questions about the adaptability of life to marginally or transiently habitable conditions.Comment: References added, text and figures updated, accepted by Ap

Ethylene regulation of fruit softening and cell wall disassembly in Charentais melon

Cell wall disassembly in ripening fruit is highly complex, involving the dismantling of multiple polysaccharide networks by diverse families of wall-modifying proteins. While it has been reported in several species that multiple members of each such family are expressed in the same fruit tissue, it is not clear whether this reflects functional redundancy, with protein isozymes from a single enzyme class performing similar roles and contributing equally to wall degradation, or whether they have discrete functions, with some isoforms playing a predominant role. Experiments reported here sought to distinguish between cell wall-related processes in ripening melon that were softening-associated and softening-independent. Cell wall polysaccharide depolymerization and the expression of wall metabolism-related genes were examined in transgenic melon (Cucumis melo var. cantalupensis Naud.) fruit with suppressed expression of the 1-aminocyclopropane-1-carboxylate oxidase (ACO) gene and fruits treated with ethylene and 1-methylcyclopropene (1-MCP). Softening was completely inhibited in the transgenic fruit but was restored by treatment with exogenous ethylene. Moreover, post-harvest application of 1-MCP after the onset of ripening completely halted subsequent softening, suggesting that melon fruit softening is ethylene-dependent. Size exclusion chromatography of cell wall polysaccharides, from the transgenic fruits, with or without exogenous ethylene, indicated that the depolymerization of both pectins and xyloglucans was also ethylene dependent. However, northern analyses of a diverse range of cell wallrelated genes, including those for polygalacturonases, xyloglucan endotransglucosylase/hydrolases, expansin, and b-galactosidases, identified specific genes within single families that could be categorized as ethylene-dependent, ethylene-independent, or partially ethylene-dependent. These results support the hypothesis that while individual cell wall-modifying proteins from each family contribute to cell wall disassembly that accompanies fruit softening, other closely related family members are regulated in an ethylene-independent manner and apparently do not directly participate in fruit softening

Pyroclastic Deposits in Floor-Fractured Craters: A Unique Style or Lunar Basaltic Volcanism?

The lunar maria were formed by effusive fissure flows of low-viscosity basalt. Regional pyroclastic deposits were formed by deep-sourced fire-fountain eruptions dominated by basaltic glass. Basaltic material is also erupted from small vents within floor-fractured impact craters. These craters are characterized by shallow, flat floors cut by radial, concentric and/or polygonal fractures. Schultz [1] identified and classified over 200 examples. Low albedo pyroclastic deposits originate from depressions along the fractures in many of these craters

Pyroclastic Deposits in the Floor-fractured Crater Alphonsus

Alphonsus, the 118 km diameter floor-fractured crater, is located immediately east of Mare Nubium. Eleven pyroclastic deposits have been identified on the crater's floor. Early telescopic spectra suggest that the floor of Alphonsus is noritic, and that the pyroclastic deposits contain mixtures of floor material and a juvenile component including basaltic glass. Head and Wilson contend that Nubium lavas intruded the breccia zone beneath Alphonsus, forming dikes and fractures on the crater floor. In this model, the magma ascended to the level of the mare but cooled underground, and a portion broke thru to the surface in vulcanian (explosive) eruptions. Alternatively, the erupted material could be from a source unrelated to the mare, in the style of regional pyroclastic deposits. High-resolution images and spectroscopy from the Moon Mineralogy Mapper (M3), Diviner Lunar Radiometer, and Lunar Reconnaissance Orbiter Camera Narrow Angle Camera (NAC) provide data to test these formation models. Spectra from M3 confirm that the crater floor is primarily composed of noritic material, and that the Nubium lavas are basaltic. Spectra from the three largest pyroclastic deposits in Alphonsus are consistent with a minor low- Ca pyroxene component in a glass-rich matrix. The centers of the 2 micron absorption bands have wavelengths too short to be of the same origin as the Nubium basalts. Diviner Christiansen feature (CF) values were used to estimate FeO abundances for the crater floor, Nubium soil, and pyroclastic deposits. The estimated abundance for the crater floor (7.5 +/- 1.4 wt.%) is within the range of FeO values for Apollo norite samples. However, the estimated FeO abundance for Nubium soil (13.4 +/- 1.4 wt.%) is lower than those measured in most mare samples. The difference may reflect contamination of the mare soil by highland ejecta. The Diviner-derived FeO abundance for the western pyroclastic deposit is 13.8 +/- 3.3 wt.%. This is lower than the values for mare soil samples, but within the range of analyzed pyroclastic glasses. The NAC images of the pyroclastic vents highlight their bright wall materials. The M3 spectra of the southeastern vent indicate that this bright material is noritic, likely crater floor material exposed by explosive eruption. These observations address the hypothesis that Nubium lavas intruded the fracture network beneath Alphonsus, leading to localized vulcanian-style eruptions. This model implies that the eruption products should be dominated by crystalline basalt fragments similar in elemental composition and mineralogy to mare lavas. The bright noritic material exposed in the vent walls is consistent with explosive eruptions. The estimated FeO abundances for the pyroclastic deposits are too low to be consistent with FeO abundances measured in mare basalts, but are within the range of pyroclastic glass samples. The visible- to near-infrared (VIS-NIR) spectra of the pyroclastic deposits and Nubium soils are significantly different, suggesting that the pyroclastics are unrelated to the mare basalts. The pyroclastic spectra are consistent with Fe-bearing glass plus small amounts of noritic wall rock. Similar glassy materials dominate regional pyroclastic deposits, suggesting a deep source for the pyroclastics observed in Alphonsus

Survival of veterans treated with enzalutamide and abiraterone for metastatic castrate resistant prostate cancer based on comorbid diseases

BACKGROUND: Comorbid diseases influence patient outcomes, yet little is known about how comorbidities interact with treatments for metastatic castrate-resistant prostate cancer (mCRPC). No head-to-head trials have compared the efficacy of abiraterone and enzalutamide - oral androgen-receptor targeted agents (ARTAs) for mCRPC. In patients with comorbid disease, outcomes with ARTAs may differ due to disparate mechanisms of action, adverse events, and drug interactions. METHODS: Retrospective observational study of US veterans initiating treatment for mCRPC with abiraterone or enzalutamide between September 2014 and June 2017. Treatment duration and overall survival (OS) was compared based on age and comorbid diseases. The association between ARTA and OS was assessed using Cox proportional hazards and propensity-score matched modeling while adjusting for potential confounders. Sensitivity analyses were performed based on patient age, comorbidities, and subsequent treatments for mCRPC. RESULTS: Of 5822 veterans treated for mCRPC, 43.0% initially received enzalutamide and 57.0% abiraterone. Veterans initially treated with enzalutamide versus abiraterone were older (mean 75.8 vs. 75.0 years) with higher mean Charlson comorbidity index (4.4 vs. 4.1), and higher rates of cardiovascular disease or diabetes (74.2% vs. 70.6%). In the entire population, veterans initially treated with enzalutamide had longer median OS compared to those initially treated with abiraterone (24.2 vs. 22.1 months, p = 0.001). In veterans with cardiovascular disease or diabetes, median treatment duration with enzalutamide was longer (11.4 vs. 8.6 months, p \u3c 0.001) with longer median OS compared to abiraterone (23.2 vs. 20.5 months, p \u3c 0.001). In a propensity score matched cohort, enzalutamide was associated with decreased mortality compared to abiraterone (HR 0.90, 95% CI 0.84-0.96). CONCLUSIONS: Veterans with cardiovascular disease or diabetes had longer treatment duration and OS with enzalutamide compared to abiraterone. Further study of ARTA selection may benefit men with metastatic castrate resistant prostate cancer and likely hormone sensitive prostate cancer, especially among patients with comorbid diseases

Habitable Climates: The Influence of Obliquity

Extrasolar terrestrial planets with the potential to host life might have large obliquities or be subject to strong obliquity variations. We revisit the habitability of oblique planets with an energy balance climate model (EBM) allowing for dynamical transitions to ice-covered snowball states as a result of ice-albedo feedback. Despite the great simplicity of our EBM, it captures reasonably well the seasonal cycle of global energetic fluxes at Earth's surface. It also performs satisfactorily against a full-physics climate model of a highly oblique Earth-like planet, in an unusual regime of circulation dominated by heat transport from the poles to the equator. Climates on oblique terrestrial planets can violate global radiative balance through much of their seasonal cycle, which limits the usefulness of simple radiative equilibrium arguments. High obliquity planets have severe climates, with large amplitude seasonal variations, but they are not necessarily more prone to global snowball transitions than low obliquity planets. We find that terrestrial planets with massive CO2 atmospheres, typically expected in the outer regions of habitable zones, can also be subject to such dynamical snowball transitions. Some of the snowball climates investigated for CO2-rich atmospheres experience partial atmospheric collapse. Since long-term CO2 atmospheric build-up acts as a climatic thermostat for habitable planets, partial CO2 collapse could limit the habitability of such planets. A terrestrial planet's habitability may thus depend sensitively on its short-term climatic stability.Comment: Minor changes, references added. 34 pages, 13 figures, accepted by Ap