Antiviral defense: interferons and beyond

Mice lacking the adaptor protein that initiates an antiviral response downstream of the RNA helicases retinoic acid–inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) have recently been described. These studies highlight the essential and nonredundant role of nucleic acid recognition in the induction of type I interferon production and raise important questions regarding the nature of cell-autonomous virus detection in coordinating the antiviral response

Leishmania major LACK Antigen Is Required for Efficient Vertebrate Parasitization

The Leishmania major LACK antigen is a key target of the immune response in susceptible BALB/c mice and remains a viable vaccine candidate for human leishmaniasis. We describe the genomic organization of the four lack genes in the L. major diploid genome together with results of selected lack gene targeting. Parasites containing a single lack gene in either the upstream or downstream locus grew comparably to wild-type promastigotes in vitro, but failed to parasitize BALB/c mice efficiently, even in a T cell–deficient environment. The replication of single copy lack mutants as amastigotes was attenuated in macrophages in vitro, and parasites failed to increase in numbers in immunodeficient mice, despite their persistence over months. Complementation with an additional lack copy was sufficient to induce robust lesion development, which also occurred using parasites with two lack genes. Conversely, attempts to generate lack-null parasites failed, suggesting that LACK is required for parasite viability. These data suggest that LACK is critical for effective mammalian parasitization and thus represents a potential drug target for leishmaniasis

The HST Key Project on the Extragalactic Distance Scale. XXII. The Discovery of Cepheids in NGC 1326-A

We report on the detection of Cepheids and the first distance measurement to the spiral galaxy NGC 1326-A, a member of the Fornax cluster of galaxies. We have employed data obtained with the Wide Field and Planetary Camera 2 on board the Hubble Space Telescope. Over a 49 day interval, a total of twelve V-band (F555W) and eight I-band (F814W) epochs of observation were obtained. Two photometric reduction packages, ALLFRAME and DoPHOT, have been employed to obtain photometry measures from the three Wide Field CCDs. Variability analysis yields a total of 17 Cepheids in common with both photometry datasets, with periods ranging between 10 and 50 days. Of these 14 Cepheids with high-quality lightcurves are used to fit the V and I period-luminosity relations and derive apparent distance moduli, assuming a Large Magellanic Cloud distance modulus (m-M) (LMC) = 18.50 +- 0.10 mag and color excess E(B-V) = 0.10 mag. Assuming A(V)/E(V-I) = 2.45, the DoPHOT data yield a true distance modulus to NGC 1326-A of (m-M)_0 = 31.36 +- 0.17 (random) +- 0.13 (systematic) mag, corresponding to a distance of 18.7 \pm 1.5 (random) \pm 1.2 (systematic) Mpc. The derived distance to NGC 1326-A is in good agreement with the distance derived previously to NGC 1365, another spiral galaxy member of the Fornax cluster. However the distances to both galaxies are significantly lower than to NGC 1425, a third Cepheid calibrator in the outer parts of the cluster.Comment: 33 pages A gzipped tar file containing 12 figures can be obtained from http://www.ipac.caltech.edu/H0kp/n1326a/n1326a.htm

The HST Key Project on the Extragalactic Distance Scale XVII. The Cepheid Distance to NGC 4725

The distance to NGC 4725 has been derived from Cepheid variables, as part of the Hubble Space Telescope Key Project on the Extragalactic Distance Scale. Thirteen F555W (V) and four F814W (I) epochs of cosmic-ray-split Wide Field and Planetary Camera 2 observations were obtained. Twenty Cepheids were discovered, with periods ranging from 12 to 49 days. Adopting a Large Magellanic Cloud distance modulus and extinction of 18.50+/-0.10 mag and E(V-I)=0.13 mag, respectively, a true reddening-corrected distance modulus (based on an analysis employing the ALLFRAME software package) of 30.50 +/- 0.16 (random) +/- 0.17 (systematic) mag was determined for NGC 4725. The corresponding of distance of 12.6 +/- 1.0 (random) +/- 1.0 (systematic) Mpc is in excellent agreement with that found with an independent analysis based upon the DoPHOT photometry package. With a foreground reddening of only E(V-I)=0.02, the inferred intrinsic reddening of this field in NGC 4725, E(V-I)=0.19, makes it one of the most highly-reddened, encountered by the HST Key Project, to date.Comment: To be published in The Astrophysical Journal, Vol. 512 (1999). 34 pages, LaTeX, 9 jpg figure

Constitutive Cytokine mRNAs Mark Natural Killer (NK) and NK T Cells Poised for Rapid Effector Function

Natural killer (NK) and NK T cells are tissue lymphocytes that secrete cytokines rapidly upon stimulation. Here, we show that these cells maintain distinct patterns of constitutive cytokine mRNAs. Unlike conventional T cells, NK T cells activate interleukin (IL)-4 and interferon (IFN)-γ transcription during thymic development and populate the periphery with both cytokine loci previously modified by histone acetylation. Similarly, NK cells transcribe and modify the IFN-γ gene, but not IL-4, during developmental maturation in the bone marrow. Lineage-specific patterns of cytokine transcripts predate infection and suggest evolutionary selection for invariant but distinct types of effector responses among the earliest responding lymphocytes

The Hubble Space Telescope Extragalactic Distance Scale Key Project XXIII. The Discovery of Cepheids In NGC 3319

The distance to NGC 3319 has been determined from Cepheid variable stars as part of the Hubble Space Telescope Key Project on the Extragalactic Distance Scale. Thirteen and four epochs of observations, using filters F555W (V) and F814W (I) respectively, were made with the Wide Field Planetary Camera 2. Thirty-three Cepheid variables between periods of 8 and 47 days were discovered. Adopting a Large Magellanic Cloud distance modulus of 18.50 +- 0.10 mag and extinction of E(V-I)=0.13 mag, a true reddening-corrected distance modulus (based on an analysis employing the ALLFRAME software package) of 30.78 +- 0.14 (random) +- 0.10 (systematic) mag and the extinction of E(V-I) = 0.06 mag were determined for NGC 3319. This galaxy is the last galaxy observed for the HST H0 Key Project.Comment: 22 pages. A gzipped tar file containing 16 figures can be obtained from http://www.ipac.caltech.edu/H0kp/n3319/n3319.htm

The ACS LCID project. X. The Star Formation History of IC 1613: Revisiting the Over-Cooling Problem

We present an analysis of the star formation history (SFH) of a field near the half light radius in the Local Group dwarf irregular galaxy IC 1613 based on deep Hubble Space Telescope Advanced Camera for Surveys imaging. Our observations reach the oldest main sequence turn-off, allowing a time resolution at the oldest ages of ~1 Gyr. Our analysis shows that the SFH of the observed field in IC 1613 is consistent with being constant over the entire lifetime of the galaxy. These observations rule out an early dominant episode of star formation in IC 1613. We compare the SFH of IC 1613 with expectations from cosmological models. Since most of the mass is in place at early times for low mass halos, a naive expectation is that most of the star formation should have taken place at early times. Models in which star formation follows mass accretion result in too many stars formed early and gas mass fractions which are too low today (the "over-cooling problem"). The depth of the present photometry of IC 1613 shows that, at a resolution of ~1 Gyr, the star formation rate is consistent with being constant, at even the earliest times, which is difficult to achieve in models where star formation follows mass assembly.Comment: 13 pages, 12 figures, accepted for publication in the Ap

A Database of Cepheid Distance Moduli and TRGB, GCLF, PNLF and SBF Data Useful for Distance Determinations

We present a compilation of Cepheid distance moduli and data for four secondary distance indicators that employ stars in the old stellar populations: the planetary nebula luminosity function (PNLF), the globular cluster luminosity function (GCLF), the tip of the red giant branch (TRGB), and the surface brightness fluctuation (SBF) method. The database includes all data published as of July 15, 1999. The main strength of this compilation resides in all data being on a consistent and homogeneous system: all Cepheid distances are derived using the same calibration of the period-luminosity relation, the treatment of errors is consistent for all indicators, measurements which are not considered reliable are excluded. As such, the database is ideal for inter-comparing any of the distance indicators considered, or for deriving a Cepheid calibration to any secondary distance indicator. Specifically, the database includes: 1) Cepheid distances, extinctions and metallicities; 2) apparent magnitudes of the PNLF cutoff; 3) apparent magnitudes and colors of the turnover of the GCLF (both in the V- and B-bands); 4) apparent magnitudes of the TRGB (in the I-band) and V-I colors at and 0.5 magnitudes fainter than the TRGB; 5) apparent surface brightness fluctuation magnitudes I, K', K_short, and using the F814W filter with the HST/WFPC2. In addition, for every galaxy in the database we give reddening estimates from DIRBE/IRAS as well as HI maps, J2000 coordinates, Hubble and T-type morphological classification, apparent total magnitude in B, and systemic velocity. (Abridged)Comment: Accepted for publication in the Astrophysical Journal Supplement Series. Because of space limitations, the figures included are low resolution bitmap images. Original figures can be found at http://www.astro.ucla.edu/~laura/pub.ht