Transcriptional analysis of antiviral small molecule therapeutics as agonists of the RLR pathway.

The recognition of pathogen associated molecular patterns (PAMPs) by pattern recognition receptors (PRR) during viral infection initiates the induction of antiviral signaling pathways, including activation of the Interferon Regulator Factor 3 (IRF3). We identified small molecule compounds that activate IRF3 through MAVS, thereby inhibiting infection by viruses of the families Flaviviridae (West Nile virus, dengue virus and hepatitis C virus), Filoviridae (Ebola virus), Orthomyxoviridae (influenza A virus), Arenaviridae (Lassa virus) and Paramyxoviridae (respiratory syncytial virus, Nipah virus) (1). In this study, we tested a lead compound along with medicinal chemistry-derived analogs to compare the gene transcriptional profiles induced by these molecules to that of other known MAVS-dependent IRF3 agonists. Transcriptional analysis of these small molecules revealed the induction of specific antiviral genes and identified a novel module of host driven immune regulated genes that suppress infection of a range of RNA viruses. Microarray data can be found in Gene Expression Omnibus (GSE74047).

Hypothesis for the evolution of three-helix Chl a/b and Chl a/c light-harvesting antenna proteins from two-helix and four-helix ancestors.

The nuclear-encoded Chl a/b and Chl a/c antenna proteins of photosynthetic eukaryotes are part of an extended family of proteins that also includes the early light-induced proteins (ELIPs) and the 22 kDa intrinsic protein of PS II (encoded by psbS gene). All members of this family have three transmembrane helices except for the psbS protein, which has four. The amino acid sequences of these proteins are compared and related to the three-dimensional structure of pea LHC II Type I (Kühlbrandt and Wang, Nature 350: 130-134, 1991). The similarity of psbS to the three-helix members of the family suggests that the latter arose from a four-helix ancestor that lost its C-terminal helix by deletion. Strong internal similarity between the two halves of the psbS protein suggests that it in turn arose as the result of the duplication of a gene encoding a two-helix protein. Since psbS is reported to be present in at least one cyanobacterium, the ancestral four-helix protein may have been present prior to the endosymbiotic event or events that gave rise to the photosynthetic eukaryotes. The Chl a/b and Chl a/c antenna proteins, and the immunologically-related proteins in the rhodophytes may have had a common ancestor which was present in the early photosynthetic eukaryotes, and predated their division into rhodophyte, chromophyte and chlorophyte lineages. The LHC I-LHC II divergence probably occurred before the separation of higher plants from chlorophyte algae and euglenophytes, and the different Types of LHC I and LHC II proteins arose prior to the separation of angiosperms and gymnosperms.

Ganymede: radar surface characteristics.

Radar observations of Ganymede, at X-band, show that the surface is unusually bright and has unusual polarization properties. A model of the surface based on large numbers of random ice facets (hence vacuum-ice interfaces) is able to account for these characteristics.

Radar characteristics of viking 1 landing sites.

Radar observations of Mars at centimeter wavelengths in May, June, and July 1976 provided estimates of surface roughness and reflectivity in three potential landing areas for Viking 1. Surface roughness is characterized by the distribution of surface landing slopes or tilts on lateral scales of the order of 1 to 10 meters; measurements of surface reflectivity are indicators of bulk surface density in the uppermost few centimeters. By these measures, the Viking 1 landing site at 47.5 degrees W, 22.4 degrees N is rougher than the martian average, although it may be near the martian average for elevations accessible to Viking, and is estimated to be near the Mars average in reflectivity. The AINW site at the center of Chryse Planitia, 43.5 degrees W, 23.4 degrees N, may be an area of anomalous radar characteristics, indicative of extreme, small-scale roughness, very low surface density, or a combination of these two characteristics, Low signal-to-noise ratio observations of the original Chryse site at 34 degrees W, 19.5 degrees N indicate that that area is at least twice as rough as the Mars average.

Misrepair mutagenesis in bacteriophage T4.

The T4 mutations px, y and 1206 inactivate an error-prone recombination-like repair system, reducing or abolishing mutagenesis by UV irradiation, MMS, and white light irradiation in the presence of the photosensitizer 8MOP. Both px and y increase some spontaneous mutation rates and slightly enhance proflavin mutagenesis; neither mutation affects thymineless or 2AP mutagenesis appreciably, but both mildly enhance 5BU mutagenesis. The mutation hm promotes UV, MMS, photodynamic, thymineless, and base analog mutagenesis, in addition to spontaneous base pair substitution mutation. It does not, however, markedly affect proflavin mutagenesis. The px mutation maps in the vicinity of genes 41-56, and the hm mutation maps in the vicinity of genes rI-v.

Thymineless mutagenesis in bacteriophage T4.

Thymine deprivation can be achieved in bacteriophage T4 either by the use of the thymidylate synthetase inhibitor FUdR, or by an appropriate combination of genetic blocks; both methods produce marked mutagenesis. Extensive tests of the specificity of thymineless mutagenesis reveal that only A:T base pairs are affected, and that transitions and possibly transversions are produced. This system therefore constitutes the first example of an A:T-specific mutagen. Thymineless mutagenesis in bacteriophage T4 exhibits a marked dependence upon the functional state of the DNA polymerase gene, but is largely independent of the px-y misrepair system.

Mars radar observations, a preliminary report.

Radar observations of a narrow belt of the surface of Mars, centered at 16 degrees south latitude, show a very rugged terrain, with elevation differences greater than 13 kilometers from peak to valley. For nearby points, the relative altitude is measured to 40 meters at best; the precision is worse for points at different latitudes, or widely separated in longitude, because of orbital uncertainties. Some of the larger craters have been resolved, and their depth and, in some cases, the height of the raised rim have been measured. Where high resolution photographs, are available, the correlation is excellent.