A multiprotein occupancy map of the mRNP on the 3′ end of histone mRNAs

The animal replication-dependent (RD) histone mRNAs are coordinately regulated with chromosome replication. The RD-histone mRNAs are the only known cellular mRNAs that are not polyadenylated. Instead, the mature transcripts end in a conserved stem–loop (SL) structure. This SL structure interacts with the stem–loop binding protein (SLBP), which is involved in all aspects of RD-histone mRNA metabolism. We used several genomic methods, including high-throughput sequencing of cross-linked immunoprecipitate (HITS-CLIP) to analyze the RNA-binding landscape of SLBP. SLBP was not bound to any RNAs other than histone mRNAs. We performed bioinformatic analyses of the HITS-CLIP data that included (i) clustering genes by sequencing read coverage using CVCA, (ii) mapping the bound RNA fragment termini, and (iii) mapping cross-linking induced mutation sites (CIMS) using CLIP-PyL software. These analyses allowed us to identify specific sites of molecular contact between SLBP and its RD-histone mRNA ligands. We performed in vitro crosslinking assays to refine the CIMS mapping and found that uracils one and three in the loop of the histone mRNA SL preferentially crosslink to SLBP, whereas uracil two in the loop preferentially crosslinks to a separate component, likely the 3′hExo. We also performed a secondary analysis of an iCLIP data set to map UPF1 occupancy across the RD-histone mRNAs and found that UPF1 is bound adjacent to the SLBP-binding site. Multiple proteins likely bind the 3′ end of RD-histone mRNAs together with SLBP

Detecting radiation with Juno/JIRAM

The Jupiter InfraRed Auroral Mapper (JIRAM) is an imaging spectrometer on board the NASA Juno mission. Since August 2016 JIRAM has been observing both the atmosphere and auroral features of the giant planet. JIRAM also participates in the Juno Radiation Monitoring experiment, providing dedicated imager acquisitions to measure the high- energy particle environment at Jupiter. During the last year the JIRAM team has developed a new and complementary approach to monitor the radiation using a subset of spectrometer data. We present some results obtained with this new approach

The Saturn Ring Skimmer Mission Concept: The next step to explore Saturn's rings, atmosphere, interior, and inner magnetosphere

The innovative Saturn Ring Skimmer mission concept enables a wide range of investigations that address fundamental questions about Saturn and its rings, as well as giant planets and astrophysical disk systems in general. This mission would provide new insights into the dynamical processes that operate in astrophysical disk systems by observing individual particles in Saturn's rings for the first time. The Ring Skimmer would also constrain the origin, history, and fate of Saturn's rings by determining their compositional evolution and material transport rates. In addition, the Ring Skimmer would reveal how the rings, magnetosphere, and planet operate as an inter-connected system by making direct measurements of the ring's atmosphere, Saturn's inner magnetosphere and the material owing from the rings into the planet. At the same time, this mission would clarify the dynamical processes operating in the planet's visible atmosphere and deep interior by making extensive high-resolution observations of cloud features and repeated measurements of the planet's extremely dynamic gravitational field. Given the scientific potential of this basic mission concept, we advocate that it be studied in depth as a potential option for the New Frontiers program.Comment: White paper submitted to the Planetary Science and Astrobiology Decadal Survey (submission #420

The Saturn Ring Skimmer Mission Concept: The next step to explore Saturn's rings, atmosphere, interior and inner magnetosphere

The innovative Saturn Ring Skimmer mission concept enables a wide range of investigations that address fundamental questions about Saturn and its rings, as well as giant planets and astrophysical disk systems in general. This mission would provide new insights into the dynamical processes that operate in astrophysical disk systems by observing individual particles in Saturn's rings for the first time. The Ring Skimmer would also constrain the origin, history, and fate of Saturn's rings by determining their compositional evolution and material transport rates. In addition, the Ring Skimmer would reveal how the rings, magnetosphere, and planet operate as an inter-connected system by making direct measurements of the ring's atmosphere, Saturn's inner magnetosphere and the material owing from the rings into the planet. At the same time, this mission would clarify the dynamical processes operating in the planet's visible atmosphere and deep interior by making extensive high-resolution observations of cloud features and repeated measurements of the planet's extremely dynamic gravitational field. Given the scientific potential of this basic mission concept, we advocate that it be studied in depth as a potential option for the New Frontiers program

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

A Bayesian method for calculating real-time quantitative PCR calibration curves using absolute plasmid DNA standards

<p>Abstract</p> <p>Background</p> <p>In real-time quantitative PCR studies using absolute plasmid DNA standards, a calibration curve is developed to estimate an unknown DNA concentration. However, potential differences in the amplification performance of plasmid DNA compared to genomic DNA standards are often ignored in calibration calculations and in some cases impossible to characterize. A flexible statistical method that can account for uncertainty between plasmid and genomic DNA targets, replicate testing, and experiment-to-experiment variability is needed to estimate calibration curve parameters such as intercept and slope. Here we report the use of a Bayesian approach to generate calibration curves for the enumeration of target DNA from genomic DNA samples using absolute plasmid DNA standards.</p> <p>Results</p> <p>Instead of the two traditional methods (classical and inverse), a Monte Carlo Markov Chain (MCMC) estimation was used to generate single, master, and modified calibration curves. The mean and the percentiles of the posterior distribution were used as point and interval estimates of unknown parameters such as intercepts, slopes and DNA concentrations. The software WinBUGS was used to perform all simulations and to generate the posterior distributions of all the unknown parameters of interest.</p> <p>Conclusion</p> <p>The Bayesian approach defined in this study allowed for the estimation of DNA concentrations from environmental samples using absolute standard curves generated by real-time qPCR. The approach accounted for uncertainty from multiple sources such as experiment-to-experiment variation, variability between replicate measurements, as well as uncertainty introduced when employing calibration curves generated from absolute plasmid DNA standards.</p

New Frontiers-class Uranus Orbiter: Exploring the feasibility of achieving multidisciplinary science with a mid-scale mission

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