A novel method to allow noninvasive, longitudinal imaging of the murine immune system in vivo

In vivo imaging has revolutionized understanding of the spatiotemporal complexity that subserves the generation of successful effector and regulatory immune responses. Until now, invasive surgery has been required for microscopic access to lymph nodes (LNs), making repeated imaging of the same animal impractical and potentially affecting lymphocyte behavior. To allow longitudinal in vivo imaging, we conceived the novel approach of transplanting LNs into the mouse ear pinna. Transplanted LNs maintain the structural and cellular organization of conventional secondary lymphoid organs. They participate in lymphocyte recirculation and exhibit the capacity to receive and respond to local antigenic challenge. The same LN could be repeatedly imaged through time without the requirement for surgical exposure, and the dynamic behavior of the cells within the transplanted LN could be characterized. Crucially, the use of blood vessels as fiducial markers also allowed precise re-registration of the same regions for longitudinal imaging. Thus, we provide the first demonstration of a method for repeated, noninvasive, in vivo imaging of lymphocyte behavior

Kepler-20: A Sun-like Star with Three Sub-Neptune Exoplanets and Two Earth-size Candidates

We present the discovery of the Kepler-20 planetary system, which we initially identified through the detection of five distinct periodic transit signals in the Kepler light curve of the host star 2MASSJ19104752+4220194. We find a stellar effective temperature Teff=5455+-100K, a metallicity of [Fe/H]=0.01+-0.04, and a surface gravity of log(g)=4.4+-0.1. Combined with an estimate of the stellar density from the transit light curves we deduce a stellar mass of Mstar=0.912+-0.034 Msun and a stellar radius of Rstar=0.944^{+0.060}_{-0.095} Rsun. For three of the transit signals, our results strongly disfavor the possibility that these result from astrophysical false positives. We conclude that the planetary scenario is more likely than that of an astrophysical false positive by a factor of 2e5 (Kepler-20b), 1e5 (Kepler-20c), and 1.1e3 (Kepler-20d), sufficient to validate these objects as planetary companions. For Kepler-20c and Kepler-20d, the blend scenario is independently disfavored by the achromaticity of the transit: From Spitzer data gathered at 4.5um, we infer a ratio of the planetary to stellar radii of 0.075+-0.015 (Kepler-20c) and 0.065+-0.011 (Kepler-20d), consistent with each of the depths measured in the Kepler optical bandpass. We determine the orbital periods and physical radii of the three confirmed planets to be 3.70d and 1.91^{+0.12}_{-0.21} Rearth for Kepler-20b, 10.85 d and 3.07^{+0.20}_{-0.31} Rearth for Kepelr-20c, and 77.61 d and 2.75^{+0.17}_{-0.30} Rearth for Kepler-20d. From multi-epoch radial velocities, we determine the masses of Kepler-20b and Kepler-20c to be 8.7\+-2.2 Mearth and 16.1+-3.5 Mearth, respectively, and we place an upper limit on the mass of Kepler-20d of 20.1 Mearth (2 sigma).Comment: accepted by ApJ, 58 pages, 12 figures revised Jan 2012 to correct table 2 and clarify planet parameter extractio

Planetary Candidates Observed by Kepler, III: Analysis of the First 16 Months of Data

New transiting planet candidates are identified in sixteen months (May 2009 - September 2010) of data from the Kepler spacecraft. Nearly five thousand periodic transit-like signals are vetted against astrophysical and instrumental false positives yielding 1,091 viable new planet candidates, bringing the total count up to over 2,300. Improved vetting metrics are employed, contributing to higher catalog reliability. Most notable is the noise-weighted robust averaging of multi-quarter photo-center offsets derived from difference image analysis which identifies likely background eclipsing binaries. Twenty-two months of photometry are used for the purpose of characterizing each of the new candidates. Ephemerides (transit epoch, T_0, and orbital period, P) are tabulated as well as the products of light curve modeling: reduced radius (Rp/R*), reduced semi-major axis (d/R*), and impact parameter (b). The largest fractional increases are seen for the smallest planet candidates (197% for candidates smaller than 2Re compared to 52% for candidates larger than 2Re) and those at longer orbital periods (123% for candidates outside of 50-day orbits versus 85% for candidates inside of 50-day orbits). The gains are larger than expected from increasing the observing window from thirteen months (Quarter 1-- Quarter 5) to sixteen months (Quarter 1 -- Quarter 6). This demonstrates the benefit of continued development of pipeline analysis software. The fraction of all host stars with multiple candidates has grown from 17% to 20%, and the paucity of short-period giant planets in multiple systems is still evident. The progression toward smaller planets at longer orbital periods with each new catalog release suggests that Earth-size planets in the Habitable Zone are forthcoming if, indeed, such planets are abundant.Comment: Submitted to ApJS. Machine-readable tables are available at http://kepler.nasa.gov, http://archive.stsci.edu/kepler/results.html, and the NASA Exoplanet Archiv

BALB/c Mice Deficient in CD4+ T Cell IL-4Rα Expression Control Leishmania mexicana Load although Female but Not Male Mice Develop a Healer Phenotype

Immunologically intact BALB/c mice infected with Leishmania mexicana develop non-healing progressively growing lesions associated with a biased Th2 response while similarly infected IL-4Rα-deficient mice fail to develop lesions and develop a robust Th1 response. In order to determine the functional target(s) for IL-4/IL-13 inducing non-healing disease, the course of L. mexicana infection was monitored in mice lacking IL-4Rα expression in specific cellular compartments. A deficiency of IL-4Rα expression on macrophages/neutrophils (in LysMcreIL-4Rα−/lox animals) had minimal effect on the outcome of L. mexicana infection compared with control (IL-4Rα−/flox) mice. In contrast, CD4+ T cell specific (LckcreIL-4Rα−/lox) IL-4Rα−/− mice infected with L. mexicana developed small lesions, which subsequently healed in female mice, but persisted in adult male mice. While a strong Th1 response was manifest in both male and female CD4+ T cell specific IL-4Rα−/− mice infected with L. mexicana, induction of IL-4 was manifest in males but not females, independently of CD4+ T cell IL-4 responsiveness. Similar results were obtained using pan-T cell specific (iLckcreIL-4Rα−/lox) IL-4Rα−/− mice. Collectively these data demonstrate that upon infection with L. mexicana, initial lesion growth in BALB/c mice is dependent on non-T cell population(s) responsive to IL-4/IL-13 while progressive infection is dependent on CD4+ T cells responsive to IL-4

Transit Timing Observations from Kepler: VI. Transit Timing Variation Candidates in the First Seventeen Months from Polynomial Models

Transit timing variations provide a powerful tool for confirming and characterizing transiting planets, as well as detecting non-transiting planets. We report the results an updated TTV analysis for 1481 planet candidates (Borucki et al. 2011; Batalha et al. 2012) based on transit times measured during the first sixteen months of Kepler observations. We present 39 strong TTV candidates based on long-term trends (2.8% of suitable data sets). We present another 136 weaker TTV candidates (9.8% of suitable data sets) based on excess scatter of TTV measurements about a linear ephemeris. We anticipate that several of these planet candidates could be confirmed and perhaps characterized with more detailed TTV analyses using publicly available Kepler observations. For many others, Kepler has observed a long-term TTV trend, but an extended Kepler mission will be required to characterize the system via TTVs. We find that the occurrence rate of planet candidates that show TTVs is significantly increased (~68%) for planet candidates transiting stars with multiple transiting planet candidate when compared to planet candidates transiting stars with a single transiting planet candidate.Comment: Accepted to ApJ; 9 pages, incl. 3 B&W figures, 1 table, 2 electronic datasets available as ancillary files; Includes analyses of more planet candidates; Transit times and additional figures at http://www.astro.ufl.edu/~eford/data/kepler

The EG95 Antigen of Echinococcus spp. Contains Positively Selected Amino Acids, which May Influence Host Specificity and Vaccine Efficacy

Echinococcosis is a worldwide zoonotic parasitic disease of humans and various herbivorous domestic animals (intermediate hosts) transmitted by the contact with wild and domestic carnivores (definitive hosts), mainly foxes and dogs. Recently, a vaccine was developed showing high levels of protection against one parasite haplotype (G1) of Echinococcus granulosus, and its potential efficacy against distinct parasite variants or species is still unclear. Interestingly, the EG95 vaccine antigen is a secreted glycosylphosphatydilinositol (GPI)-anchored protein containing a fibronectin type III domain, which is ubiquitous in modular proteins involved in cell adhesion. EG95 is highly expressed in oncospheres, the parasite life cycle stage which actively invades the intermediate hosts. After amplifying and sequencing the complete CDS of 57 Echinococcus isolates belonging to 7 distinct species, we uncovered a large amount of genetic variability, which may influence protein folding. Two positively selected sites are outside the vaccine epitopes, but are predicted to alter protein conformation. Moreover, phylogenetic analyses indicate that EG95 isoform evolution is convergent with regard to the number of beta-sheets and alpha-helices. We conclude that having a variety of EG95 isoforms is adaptive for Echinococcus parasites, in terms of their ability to invade different hosts, and we propose that a mixture of isoforms could possibly maximize vaccine efficacy

Validating AU Microscopii d with Transit Timing Variations

AU Mic is a young (22 Myr), nearby exoplanetary system that exhibits excess transit timing variations (TTVs) that cannot be accounted for by the two known transiting planets nor stellar activity. We present the statistical “validation” of the tentative planet AU Mic d (even though there are examples of “confirmed” planets with ambiguous orbital periods). We add 18 new transits and nine midpoint times in an updated TTV analysis to prior work. We perform the joint modeling of transit light curves using EXOFASTv2 and extract the transit midpoint times. Next, we construct an O − C diagram and use Exo-Striker to model the TTVs. We generate TTV log-likelihood periodograms to explore possible solutions for d’s period, then follow those up with detailed TTV and radial velocity Markov Chain Monte Carlo modeling and stability tests. We find several candidate periods for AU Mic d, all of which are near resonances with AU Mic b and c of varying order. Based on our model comparisons, the most-favored orbital period of AU Mic d is 12.73596 ± 0.00793 days ( T _C _,d = 2458340.55781 ± 0.11641 BJD), which puts the three planets near 4:6:9 mean-motion resonance. The mass for d is 1.053 ± 0.511 M _⊕ , making this planet Earth-like in mass. If confirmed, AU Mic d would be the first known Earth-mass planet orbiting a young star and would provide a valuable opportunity in probing a young terrestrial planet’s atmosphere. Additional TTV observations of the AU Mic system are needed to further constrain the planetary masses, search for possible transits of AU Mic d, and detect possible additional planets beyond AU Mic c

TOI-431/HIP 26013: A super-Earth and a sub-Neptune transiting a bright, early K dwarf, with a third RV planet

We present the bright (Vmag = 9.12), multiplanet system TOI-431, characterized with photometry and radial velocities (RVs). We estimate the stellar rotation period to be 30.5 ± 0.7 d using archival photometry and RVs. Transiting Exoplanet Survey Satellite (TESS) objects of Interest (TOI)-431 b is a super-Earth with a period of 0.49 d, a radius of 1.28 ± 0.04 R, a mass of 3.07 ± 0.35 M, and a density of 8.0 ± 1.0 g cm-3; TOI-431 d is a sub-Neptune with a period of 12.46 d, a radius of 3.29 ± 0.09 R, a mass of 9.90+1.53-1.49 M, and a density of 1.36 ± 0.25 g cm-3. We find a third planet, TOI-431 c, in the High Accuracy Radial velocity Planet Searcher RV data, but it is not seen to transit in the TESS light curves. It has an Msin i of 2.83+0.41-0.34 M, and a period of 4.85 d. TOI-431 d likely has an extended atmosphere and is one of the most well-suited TESS discoveries for atmospheric characterization, while the super-Earth TOI-431 b may be a stripped core. These planets straddle the radius gap, presenting an interesting case-study for atmospheric evolution, and TOI-431 b is a prime TESS discovery for the study of rocky planet phase curves.Fil: Osborn, Ares. University of Warwick; Reino UnidoFil: Armstrong, David J. University of Warwick; Reino UnidoFil: Cale, Bryson. George Mason University; Estados UnidosFil: Brahm, Rafael. Universidad Adolfo Ibañez; Chile. Instituto de Astrofísica; ChileFil: Wittenmyer, Robert A. University Of Southern Queensland; AustraliaFil: Dai, Fei. Division Of Geological And Planetary Sciences; Estados UnidosFil: Crossfield, Ian J. M. University of Kansas; Estados UnidosFil: Bryant, Edward M. University of Warwick; Reino UnidoFil: Adibekyan, Vardan. Universidad de Porto; PortugalFil: Cloutier, Ryan. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Collins, Karen A. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Delgado Mena, E.. Universidad de Porto; PortugalFil: Fridlund, Malcolm. Leiden University; Países Bajos. Chalmers University of Technology; SueciaFil: Hellier, Coel. Keele University; Reino UnidoFil: Howell, Steve B. NASA Ames Research Center; Estados UnidosFil: King, George W. University of Warwick; Reino UnidoFil: Lillo Box, Jorge. Consejo Superior de Investigaciones Científicas. Centro de Astrobiología; EspañaFil: Otegi, Jon. Universidad de Ginebra; Suiza. Universitat Zurich; SuizaFil: Sousa, S.. Universidad de Porto; PortugalFil: Stassun, Keivan G. Vanderbilt University; Estados UnidosFil: Matthews, Elisabeth C. Universidad de Ginebra; Suiza. Massachusetts Institute of Technology; Estados UnidosFil: Ziegler, Carl. University of Toronto; CanadáFil: Ricker, George. Massachusetts Institute of Technology; Estados UnidosFil: Vanderspek, Roland. Massachusetts Institute of Technology; Estados UnidosFil: Latham, David W. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Seager, S.. Massachusetts Institute of Technology; Estados UnidosFil: Winn, Joshua N.. University of Princeton; Estados UnidosFil: Jenkins, Jon M. NASA Ames Research Center; Estados UnidosFil: Acton, Jack S. University of Leicester; Reino UnidoFil: Addison, Brett C. University Of Southern Queensland; AustraliaFil: Diaz, Rodrigo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias Físicas. - Universidad Nacional de San Martín. Instituto de Ciencias Físicas; Argentin