The immune response to Mycobacterium tuberculosis infection determines tuberculosis disease outcomes, yet we have an incomplete understanding of what immune factors contribute to a protective immune ...response. Neutrophilic inflammation has been associated with poor disease prognosis in humans and in animal models during M. tuberculosis infection and, therefore, must be tightly regulated. ATG5 is an essential autophagy protein that is required in innate immune cells to control neutrophil-dominated inflammation and promote survival during M. tuberculosis infection; however, the mechanistic basis for how ATG5 regulates neutrophil recruitment is unknown. To interrogate what innate immune cells require ATG5 to control neutrophil recruitment during M. tuberculosis infection, we used different mouse strains that conditionally delete Atg5 in specific cell types. We found that ATG5 is required in CD11c+ cells (lung macrophages and dendritic cells) to control the production of proinflammatory cytokines and chemokines during M. tuberculosis infection, which would otherwise promote neutrophil recruitment. This role for ATG5 is autophagy dependent, but independent of mitophagy, LC3-associated phagocytosis, and inflammasome activation, which are the most well-characterized ways that autophagy proteins regulate inflammation. In addition to the increased proinflammatory cytokine production from macrophages during M. tuberculosis infection, loss of ATG5 in innate immune cells also results in an early induction of TH17 responses. Despite prior published in vitro cell culture experiments supporting a role for autophagy in controlling M. tuberculosis replication in macrophages, the effects of autophagy on inflammatory responses occur without changes in M. tuberculosis burden in macrophages. These findings reveal new roles for autophagy proteins in lung resident macrophages and dendritic cells that are required to suppress inflammatory responses that are associated with poor control of M. tuberculosis infection.
GEOHAB Kudela, Raphael M.; Berdalet, Elisa; Enevoldsen, Henrik ...
Oceanography (Washington, D.C.),
03/2017, Letnik:
30, Številka:
1
Journal Article
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In 2001, the first international research program focusing exclusively on harmful marine algae, GEOHAB (Global Ecology and Oceanography of Harmful Algal Blooms), was established by the HAB research ...community, under the sponsorship of the Intergovernmental Oceanographic Commission of UNESCO and the Scientific Committee on Oceanic Research. Its mission was to foster international cooperation to advance understanding of HAB dynamics and to improve our ability to predict them. The main efforts were focused on (1) the physiological, behavioral, and genetic characteristics of harmful microalgal species, and (2) the interactions between physical and other environmental conditions that promote the success of one group of species over another. GEOHAB was designed to study HABs with a view to integrating global data from comparable ecosystems. With an international, multidisciplinary, and comparative approach, GEOHAB advanced our understanding of the mechanisms underlying population dynamics of HABs within an ecological and oceanographic context and from an ecosystem perspective at the regional scale. GEOHAB encouraged combined experimental, observational, and modeling tools, using both existing and innovative technologies in a multidisciplinary approach, consistent with the multiple scales and oceanographic complexity of HAB phenomena. GEOHAB established the basis for continued international efforts now and into the future in order to better understand and predict the global complex phenomena of harmful algal blooms.
The National Oceanic and Atmospheric Administration Marine Fisheries Service endeavors to manage fish stocks with an ecosystem perspective. This objective requires an understanding of the effects of ...the environment and fishing on all major ecosystem components. For example, in large upwelling systems like the California Current Ecosystem (CCE), natural cycles in the oceanographic and atmospheric conditions appear to drive large fluctuations in the distributions and relative abundances of coastal pelagic fish species (CPS), for example, sardine, anchovy, mackerels, and herring. These changes may be accelerated or delayed by changes in mortality due to fishing or predation of larger fish, marine mammals, and seabirds. We suggest that the data necessary to manage CPS with an ecosystem perspective may be obtained from frequent surveys of multiple CPS and their biotic and abiotic environment. We show that this is practical with surveys based on a combination of acoustic and trawl sampling coupled with complementary measures from numerous other sensors. Such acoustic-trawl-method (ATM) surveys of the CCE were conducted during the spring and summer of 2012 and 2013. We present the results of these surveys, including the seasonal distributions and abundances of multiples of the most ecological and economically important CPS. These data hint at the ultimate potential of periodic surveys using ATM sampling augmented with physical oceanographic, zooplankton, ichthyoplankton, fish, seabird, and mammal investigations to characterize the ecosystems.
The Blanco Cosmology Survey (BCS) is a 60 night imaging survey of ~80 deg super(2) of the southern sky located in two fields: (alpha, delta) = (5 hr, -55degrees) and (23 hr, -55degrees). The survey ...was carried out between 2005 and 2008 in griz bands with the Mosaic2 imager on the Blanco 4 m telescope. The primary aim of the BCS survey is to provide the data required to optically confirm and measure photometric redshifts for Sunyaev-Zel'dovich effect selected galaxy clusters from the South Pole Telescope and the Atacama Cosmology Telescope. We process and calibrate the BCS data, carrying out point-spread function-corrected model-fitting photometry for all detected objects. The median 10sigma galaxy (point-source) depths over the survey in griz are approximately 23.3 (23.9), 23.4 (24.0), 23.0 (23.6), and 21.3 (22.1), respectively. The astrometric accuracy relative to the USNO-B survey is ~45 mas. We calibrate our absolute photometry using the stellar locus in grizJ bands, and thus our absolute photometric scale derives from the Two Micron All Sky Survey, which has ~2% accuracy. The scatter of stars about the stellar locus indicates a systematic floor in the relative stellar photometric scatter in griz that is ~1.9%, ~2.2%, ~2.7%, and ~2.7%, respectively. A simple cut in the AstrOmatic star-galaxy classifier spread_model produces a star sample with good spatial uniformity. We use the resulting photometric catalogs to calibrate photometric redshifts for the survey and demonstrate scatter deltaz/(1 + z) = 0.054 with an outlier fraction eta < 5% to z ~ 1. We highlight some selected science results to date and provide a full description of the released data products.
Kepler constraints on planets near hot Jupiters Steffen, Jason H; Ragozzine, Darin; Fabrycky, Daniel C ...
Proceedings of the National Academy of Sciences - PNAS,
05/2012, Letnik:
109, Številka:
21
Journal Article
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We present the results of a search for planetary companions orbiting near hot Jupiter planet candidates (Jupiter-size candidates with orbital periods near 3 d) identified in the Kepler data through ...its sixth quarter of science operations. Special emphasis is given to companions between the 2:1 interior and exterior mean-motion resonances. A photometric transit search excludes companions with sizes ranging from roughly two-thirds to five times the size of the Earth, depending upon the noise properties of the target star. A search for dynamically induced deviations from a constant period (transit timing variations) also shows no significant signals. In contrast, comparison studies of warm Jupiters (with slightly larger orbits) and hot Neptune-size candidates do exhibit signatures of additional companions with these same tests. These differences between hot Jupiters and other planetary systems denote a distinctly different formation or dynamical history.
We describe searches for B meson decays to the charmless vector-vector final states omega omega and omega phi with 471 x 10^6 B Bbar pairs produced in e+ e- annihilation at sqrt(s) = 10.58 GeV using ...the BABAR detector at the PEP-II collider at the SLAC National Accelerator Laboratory. We measure the branching fraction B(B0 --> omega omega) = (1.2 +- 0.3 +0.3-0.2) x 10^-6, where the first uncertainty is statistical and the second is systematic, corresponding to a significance of 4.4 standard deviations. We also determine the upper limit B(B0 --> omega phi) < 0.7 x 10^-6 at 90% confidence level. These measurements provide the first evidence for the decay B0 --> omega omega, and an improvement of the upper limit for the decay B0 --> omega phi.
Results are presented of single crystal structural, thermodynamic, and reflectivity measurements of the double-perovskite Ba2NaOsO6. These characterize the material as a 5d1 ferromagnetic Mott ...insulator with an ordered moment of approximately 0.2microB per formula unit and TC=6.8(3) K. The magnetic entropy associated with this phase transition is close to Rln2, indicating that the quartet ground state anticipated from consideration of the crystal structure is split, consistent with a scenario in which the ferromagnetism is associated with orbital ordering.
We analyze the rise and fall times of Type Ia supernova (SN Ia) light curves discovered by the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey. From a set of 391 light curves k-corrected to ...the rest-frame B and V bands, we find a smaller dispersion in the rising portion of the light curve compared to the decline. This is in qualitative agreement with computer models which predict that variations in radioactive nickel yield have less impact on the rise than on the spread of the decline rates. The differences we find in the rise and fall properties suggest that a single 'stretch' correction to the light curve phase does not properly model the range of SN Ia light curve shapes. We select a subset of 105 light curves well observed in both rise and fall portions of the light curves and develop a '2-stretch' fit algorithm which estimates the rise and fall times independently. We find the average time from explosion to B-band peak brightness is 17.38 {+-} 0.17 days, but with a spread of rise times which range from 13 days to 23 days. Our average rise time is shorter than the 19.5 days found in previous studies; this reflects both the different light curve template used and the application of the 2-stretch algorithm. The SDSS-II supernova set and the local SNe Ia with well-observed early light curves show no significant differences in their average rise-time properties. We find that slow-declining events tend to have fast rise times, but that the distribution of rise minus fall time is broad and single peaked. This distribution is in contrast to the bimodality in this parameter that was first suggested by Strovink (2007) from an analysis of a small set of local SNe Ia. We divide the SDSS-II sample in half based on the rise minus fall value, t{sub r} - t{sub f} {approx}< 2 days and t{sub r} - t{sub f} > 2 days, to search for differences in their host galaxy properties and Hubble residuals; we find no difference in host galaxy properties or Hubble residuals in our sample.
Structural Basis of Ribozyme-Catalyzed RNA Assembly Robertson, Michael P; Scott, William G
Science (American Association for the Advancement of Science),
03/2007, Letnik:
315, Številka:
5818
Journal Article
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Life originated, according to the RNA World hypothesis, from self-replicating ribozymes that catalyzed ligation of RNA fragments. We have solved the 2.6 angstrom crystal structure of a ligase ...ribozyme that catalyzes regiospecific formation of a 5' to 3' phosphodiester bond between the 5'-triphosphate and the 3'-hydroxyl termini of two RNA fragments. Invariant residues form tertiary contacts that stabilize a flexible stem of the ribozyme at the ligation site, where an essential magnesium ion coordinates three phosphates. The structure of the active site permits us to suggest how transition-state stabilization and a general base may catalyze the ligation reaction required for prebiotic RNA assembly.