Atmospheric, Orbital, and Eclipse-Depth Analysis of the Hot Jupiter HAT-P-30-WASP-51Ab

HAT-P-30-WASP-51b is a hot-Jupiter exoplanet that orbits an F star every 2.8106 days at a distance of 0.0419 AU. Using the Spitzer Space Telescope in 2012 (Spitzer Program Number 70084) we observed two secondary eclipses at 3.6 and 4.5 μm. We present eclipse-depth measurements of 0.177 ± 0.018 % and 0.247 ± 0.024 % and estimate the infrared brightness temperatures to be 1990 ± 110 K and 2080 ± 130 K for these two channels, respectively, from an analysis using our Photometry for Orbits, Eclipses, and Transits (POET) pipeline. These may be grazing eclipses. We also refine its orbit using our own secondary-eclipse measurements in combination with radial- velocity and transit observations from both professional and amateur observers. Using only the phase of our secondary eclipses, we can constrain e cos(ω) where e is the orbital eccentricity and ω is the argument of periastron to 0.0058 ± 0.00094. This is the component of eccentricity in the plane of view,. This small but non-zero eccentricity is independent of the effects that stellar tides have on radial-velocity data. When including radial velocity data in our model, our Markov chain finds an e cos(ω) of 0.0043 ± 0.0007. We constrain the atmospheric temperature profile using our Bayesian Atmospheric Radiative Transfer code (BART), a large lower bound (700 km) for the scale height, and the potential for high quality transit spectroscopy observations

Competition of Escherichia coli DNA Polymerases I, II and III with DNA Pol IV in Stressed Cells

Escherichia coli has five DNA polymerases, one of which, the low-fidelity Pol IV or DinB, is required for stress-induced mutagenesis in the well-studied Lac frameshift-reversion assay. Although normally present at ∼200 molecules per cell, Pol IV is recruited to acts of DNA double-strand-break repair, and causes mutagenesis, only when at least two cellular stress responses are activated: the SOS DNA-damage response, which upregulates DinB ∼10-fold, and the RpoS-controlled general-stress response, which upregulates Pol IV about 2-fold. DNA Pol III was also implicated but its role in mutagenesis was unclear. We sought in vivo evidence on the presence and interactions of multiple DNA polymerases during stress-induced mutagenesis. Using multiply mutant strains, we provide evidence of competition of DNA Pols I, II and III with Pol IV, implying that they are all present at sites of stress-induced mutagenesis. Previous data indicate that Pol V is also present. We show that the interactions of Pols I, II and III with Pol IV result neither from, first, induction of the SOS response when particular DNA polymerases are removed, nor second, from proofreading of DNA Pol IV errors by the editing functions of Pol I or Pol III. Third, we provide evidence that Pol III itself does not assist with but rather inhibits Pol IV-dependent mutagenesis. The data support the remaining hypothesis that during the acts of DNA double-strand-break (DSB) repair, shown previously to underlie stress-induced mutagenesis in the Lac system, there is competition of DNA polymerases I, II and III with DNA Pol IV for action at the primer terminus. Up-regulation of Pol IV, and possibly other stress-response-controlled factor(s), tilt the competition in favor of error-prone Pol IV at the expense of more accurate polymerases, thus producing stress-induced mutations. This mutagenesis assay reveals the DNA polymerases operating in DSB repair during stress and also provides a sensitive indicator for DNA polymerase competition and choice in vivo

Genome-Wide Analysis of Transcriptional Reprogramming in Mouse Models of Acute Myeloid Leukaemia

Acute leukaemias are commonly caused by mutations that corrupt the transcriptional circuitry of haematopoietic stem/progenitor cells. However, the mechanisms underlying large-scale transcriptional reprogramming remain largely unknown. Here we investigated transcriptional reprogramming at genome-scale in mouse retroviral transplant models of acute myeloid leukaemia (AML) using both gene-expression profiling and ChIP-sequencing. We identified several thousand candidate regulatory regions with altered levels of histone acetylation that were characterised by differential distribution of consensus motifs for key haematopoietic transcription factors including Gata2, Gfi1 and Sfpi1/Pu.1. In particular, downregulation of Gata2 expression was mirrored by abundant GATA motifs in regions of reduced histone acetylation suggesting an important role in leukaemogenic transcriptional reprogramming. Forced re-expression of Gata2 was not compatible with sustained growth of leukaemic cells thus suggesting a previously unrecognised role for Gata2 in downregulation during the development of AML. Additionally, large scale human AML datasets revealed significantly higher expression of GATA2 in CD34+ cells from healthy controls compared with AML blast cells. The integrated genome-scale analysis applied in this study represents a valuable and widely applicable approach to study the transcriptional control of both normal and aberrant haematopoiesis and to identify critical factors responsible for transcriptional reprogramming in human cancer

Administration of Bleomycin via the Oropharyngeal Aspiration Route Leads to Sustained Lung Fibrosis in Mice and Rats as Quantified by UTE-MRI and Histology

Pulmonary fibrosis can be experimentally induced in small rodents by bleomycin. The antibiotic is usually administered via the intratracheal or intranasal routes. In the present study, we investigated the oropharyngeal aspiration of bleomycin as an alternative route for the induction of lung fibrosis in rats and mice. The development of lung injury was followed in vivo by ultrashort echo time magnetic resonance imaging (UTE-MRI) and by post-mortem analyses (histology of collagen, hydroxyproline determination, and qRT-PCR). In C57BL/6 mice, oropharyngeal aspiration of bleomycin led to more prominent lung fibrosis as compared to intranasal administration. Consequently, the oropharyngeal aspiration route allowed a dose reduction of bleomycin and, therewith, a model refinement. Moreover, the distribution of collagen after oropharyngeal aspiration of bleomycin was more homogenous than after intranasal administration: for the oropharyngeal aspiration route, fibrotic areas appeared all over the lung lobes, while for the intranasal route fibrotic lesions appeared mainly around the largest superior airways. Thus, oropharyngeal aspiration of bleomycin induced morphological changes that were more comparable to the human disease than the intranasal administration route did. Oropharyngeal aspiration of bleomycin led to a homogeneous fibrotic injury also in rat lungs. The present data suggest oropharyngeal aspiration of bleomycin as a less invasive means to induce homogeneous and sustained fibrosis in the lungs of mice and rats

Hallmarks of 'BRCAness' in sporadic cancers.

Hallmarks of 'BRCAness' in sporadic cancers Germline mutations in the BRCA1, BRCA2 and Fanconi anaemia genes confer cancer susceptibility, and the proteins encoded by these genes have distinct functions in related DNA-repair processes. Emerging evidence indicates that these processes are disrupted by numerous mechanisms in sporadic cancers. Collectively, there are properties that define 'BRCAness' - that is, traits that some sporadic cancers share with those occurring in either BRCA1- or BRCA2-mutation carriers. These common properties might have important implications for the clinical management of these cancers