Genome landscapes and bacteriophage codon usage

Across all kingdoms of biological life, protein-coding genes exhibit unequal usage of synonmous codons. Although alternative theories abound, translational selection has been accepted as an important mechanism that shapes the patterns of codon usage in prokaryotes and simple eukaryotes. Here we analyze patterns of codon usage across 74 diverse bacteriophages that infect E. coli, P. aeruginosa and L. lactis as their primary host. We introduce the concept of a `genome landscape,' which helps reveal non-trivial, long-range patterns in codon usage across a genome. We develop a series of randomization tests that allow us to interrogate the significance of one aspect of codon usage, such a GC content, while controlling for another aspect, such as adaptation to host-preferred codons. We find that 33 phage genomes exhibit highly non-random patterns in their GC3-content, use of host-preferred codons, or both. We show that the head and tail proteins of these phages exhibit significant bias towards host-preferred codons, relative to the non-structural phage proteins. Our results support the hypothesis of translational selection on viral genes for host-preferred codons, over a broad range of bacteriophages.Comment: 9 Color Figures, 5 Tables, 53 Reference

Radiolocalisation and imaging of stably HPLAP-transfected MO4 tumours with monoclonal antibodies and fragments.

Immunotargeting of PLAP-expressing tumours was studied for two radioiodinated, highly specific anti-PLAP monoclonal antibodies, 7E8 and 17E3, differing 10-fold in affinity, as well as for 7E8 F(ab')2 fragments. An anti-CEA monoclonal antibody or anti-CD3 F(ab')2 fragments were used as controls. Specific and non-specific targeting was examined in nude mice simultaneously grafted with PLAP-positive tumours derived from MO4 1-4 cells, and CEA-positive tumours, derived from 5583-S cells. Results indicated that (1) MO4 1-4 tumours, with a stable expression of PLAP on the plasma membrane, represent a useful new in vivo model for immunodirected tumour targeting; (2) differences in antibody affinity for PLAP in vitro are not reflected in antibody avidity for tumour cells in vivo; and (3) excellent selective and specific localisation of the PLAP-positive tumours is achieved when 7E8 F(ab')2 fragments are used. The high tumour/blood ratios (10.7 +/- 3.9 at 46 h after injection) were due to a much faster blood clearance of 7E8 F(ab')2 fragments. At this time point, the mean tumour/non-tumour tissue ratio was as high as 34.5, and the mean specific localisation index was 29.0. As expected, the F(ab')2 fragments provided high tumour imaging efficiency on gamma camera recording. These data imply important potentials of the PLAP/anti-PLAP system for immunolocalisation and therapy in patients, but also emphasise that in vitro criteria alone are not reflected in in vivo tumour localisation capacities of antibodies

A New Understanding of the Europa Atmosphere and Limits on Geophysical Activity

Deep extreme ultraviolet spectrograph exposures of the plasma sheet at the orbit of Europa, obtained in 2001 using the Cassini Ultraviolet Imaging Spectrograph experiment, have been analyzed to determine the state of the gas. The results are in basic agreement with earlier results, in particular with Voyager encounter measurements of electron density and temperature. Mass loading rates and lack of detectable neutrals in the plasma sheet, however, are in conflict with earlier determinations of atmospheric composition and density at Europa. A substantial fraction of the plasma species at the Europa orbit are long-lived sulfur ions originating at Io, with ~25% derived from Europa. During the outward radial diffusion process to the Europa orbit, heat deposition forces a significant rise in plasma electron temperature and latitudinal size accompanied with conversion to higher order ions, a clear indication that mass loading from Europa is very low. Analysis of far ultraviolet spectra from exposures on Europa leads to the conclusion that earlier reported atmospheric measurements have been misinterpreted. The results in the present work are also in conflict with a report that energetic neutral particles imaged by the Cassini ion and neutral camera experiment originate at the Europa orbit. An interpretation of persistent energetic proton pitch angle distributions near the Europa orbit as an effect of a significant population of neutral gas is also in conflict with the results of the present work. The general conclusion drawn here is that Europa is geophysically far less active than inferred in previous research, with mass loading of the plasma sheet ≤4.5 x 10^(25) atoms s^(-1) two orders of magnitude below earlier published calculations. Temporal variability in the region joining the Io and Europa orbits, based on the accumulated evidence, is forced by the response of the system to geophysical activity at Io. No evidence for the direct injection of H_2O into the Europa atmosphere or from Europa into the magnetosphere system, as has been observed at Enceladus in the Saturn system, is obtained in the present investigation

Equilibrium Sampling From Nonequilibrium Dynamics

We present some applications of an Interacting Particle System (IPS) methodology to the field of Molecular Dynamics. This IPS method allows several simulations of a switched random process to keep closer to equilibrium at each time, thanks to a selection mechanism based on the relative virtual work induced on the system. It is therefore an efficient improvement of usual non-equilibrium simulations, which can be used to compute canonical averages, free energy differences, and typical transitions paths

NASA Planetary Mission Concept Study: Assessing: Dwarf Planet Ceres' past and Present Habitability Potential

The Dawn mission revolutionized our understanding of Ceres during the same decade that has also witnessed the rise of ocean worlds as a research and exploration focus. We will report progress on the Planetary Mission Concept Study (PMCS) on the future exploration of Ceres under the New Frontiers or Flagship program that was selected for NASA funding in October 2019. At the time this writing, the study was just kicked off, hence this abstract reports the study plan as presented in the proposal