Cryptococcal Cell Morphology Affects Host Cell Interactions and Pathogenicity

Cryptococcus neoformans is a common life-threatening human fungal pathogen. The size of cryptococcal cells is typically 5 to 10 µm. Cell enlargement was observed in vivo, producing cells up to 100 µm. These morphological changes in cell size affected pathogenicity via reducing phagocytosis by host mononuclear cells, increasing resistance to oxidative and nitrosative stress, and correlated with reduced penetration of the central nervous system. Cell enlargement was stimulated by coinfection with strains of opposite mating type, and ste3aΔ pheromone receptor mutant strains had reduced cell enlargement. Finally, analysis of DNA content in this novel cell type revealed that these enlarged cells were polyploid, uninucleate, and produced daughter cells in vivo. These results describe a novel mechanism by which C. neoformans evades host phagocytosis to allow survival of a subset of the population at early stages of infection. Thus, morphological changes play unique and specialized roles during infection

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Search for high-energy neutrino emission from hard X-ray AGN with IceCube

Active Galactic Nuclei (AGN) are powerful astronomical objects with very high luminosities. Theoretical arguments suggest that these objects are capable of accelerating particles to energies of 1020 eV. In environments with matter or photon targets, cosmic-ray interactions transpire leading to the production of pionic gamma rays and neutrinos. Since the AGN environment is rich in gas, dust and photons, they are promising candidate sources of high-energy astrophysical neutrinos. While the neutrinos manage to escape, the gamma rays may further interact and cascade down to hard X-rays in environments with sufficiently large photon or gas targets. We have used 12 years of IceCube data to perform a stacked search and a point source search for high-energy neutrino emission from hard X-ray AGN sampled from Swift-BAT Spectroscopic Survey (BASS) and present the results of these two analyses

Association of forced expiratory volume with disease duration and sputum neutrophils in chronic asthma

<b>Purpose</b> Some patients with chronic asthma develop irreversible airflow obstruction. Our aim was to assess whether reported duration of asthma and induced sputum cell counts were associated with pulmonary function in patients with asthma who did not smoke.<p></p> <b>Subjects and methods</b> Maximal forced expiratory volume in the first second (FEV<sub>1</sub>) was determined following a steroid trial (oral prednisolone, 30 mg/d [n = 92 patients]; or inhaled fluticasone, 2000 μg/d [n = 5]; for 2 weeks) and 2.5 mg of nebulized albuterol. Asthma history was recorded with duration from first diagnosis. All subjects were nonsmokers, or were to have stopped smoking ≥5 years previously and smoked ≤5 pack-years (n = 12). Induced sputum was obtained from 59 subjects for analysis of airway cell counts.<p></p> <b>Results</b> Maximal FEV<sub>1</sub> was inversely associated with asthma duration (r = −0.47, P <0.0001), age (r = −0.40, P <0.0001), and the proportion of sputum neutrophils (r<sub>s</sub> = −0.50, P = 0.00004). After adjusting for age, both duration of disease and sputum neutrophils were independently associated with maximal FEV<sub>1</sub>. Neutrophil activation, as measured by sputum myeloperoxidase levels, was positively associated with the proportion of sputum neutrophils (r<sub>s</sub> = 0.45, P = 0.0004) and inversely associated with maximal FEV<sub>1</sub> (r<sub>s</sub> = −0.59, P <0.0001).<p></p> <b>Conclusion</b> Long disease duration may be a predisposing factor for the development of irreversible airflow obstruction in patients with chronic asthma. The negative associations of sputum neutrophil count and activation with maximal FEV<sub>1</sub> suggest that neutrophils may be involved in the pathophysiology of irreversible airflow obstruction in asthma.<p></p&gt