Comparative Genomic Analysis of Pathogenic and Probiotic Enterococcus faecalis Isolates, and Their Transcriptional Responses to Growth in Human Urine

Urinary tract infection (UTI) is the most common infection caused by enterococci, and Enterococcus faecalis accounts for the majority of enterococcal infections. Although a number of virulence related traits have been established, no comprehensive genomic or transcriptomic studies have been conducted to investigate how to distinguish pathogenic from non-pathogenic E. faecalis in their ability to cause UTI. In order to identify potential genetic traits or gene regulatory features that distinguish pathogenic from non-pathogenic E. faecalis with respect to UTI, we have performed comparative genomic analysis, and investigated growth capacity and transcriptome profiling in human urine in vitro. Six strains of different origins were cultivated and all grew readily in human urine. The three strains chosen for transcriptional analysis showed an overall similar response with respect to energy and nitrogen metabolism, stress mechanism, cell envelope modifications, and trace metal acquisition. Our results suggest that citrate and aspartate are significant for growth of E. faecalis in human urine, and manganese appear to be a limiting factor. The majority of virulence factors were either not differentially regulated or down-regulated. Notably, a significant up-regulation of genes involved in biofilm formation was observed. Strains from different origins have similar capacity to grow in human urine. The overall similar transcriptional responses between the two pathogenic and the probiotic strain suggest that the pathogenic potential of a certain E. faecalis strain may to a great extent be determined by presence of fitness and virulence factors, rather than the level of expression of such traits

KELT-17B: A HOT-JUPITER TRANSITING AN A-STAR IN A MISALIGNED ORBIT DETECTED WITH DOPPLER TOMOGRAPHY

We present the discovery of a hot-Jupiter transiting the V=9.23 mag main-sequence A-star KELT-17 (BD+14 1881). KELT-17b is a 1.31 -0.29/+0.28 Mj, 1.525 -0.060/+0.065 Rj hot-Jupiter in a 3.08 day period orbit misaligned at -115.9 +/- 4.1 deg to the rotation axis of the star. The planet is confirmed via both the detection of the radial velocity orbit, and the Doppler tomographic detection of the shadow of the planet over two transits. The nature of the spin-orbit misaligned transit geometry allows us to place a constraint on the level of differential rotation in the host star; we find that KELT-17 is consistent with both rigid-body rotation and solar differential rotation rates (alpha < 0.30 at 2 sigma significance). KELT-17 is only the fourth A-star with a confirmed transiting planet, and with a mass of 1.635 -0.061/+0.066 Msun, effective temperature of 7454 +/- 49 K, and projected rotational velocity v sin I_* = 44.2 -1.3/+1.5 km/s; it is amongst the most massive, hottest, and most rapidly rotating of known planet hosts.Comment: 15 pages, 9 figures, accepted for publication in A

VizieR Online Data Catalog: CANDELS visual classifications for GOODS-S (Kartaltepe+, 2015)

The Cosmic Assembly Near-infrared Dark Energy Legacy Survey (CANDELS) is an HST Multi-Cycle Treasury Program to image portions of five of the most commonly studied legacy fields (GOODS-N, GOODS-S, COSMOS, UDS and EGS) with WFC3 in the NIR. The survey has observed all five fields to 2-orbit depth in F125W (J-band, 2/3 orbit) and F160W (H-band, 4/3 orbit) and the central regions of GOODS-N and GOODS-S to 10 orbit depth in these bands as well as F105W (Y-band). ACS parallel imaging has also been obtained for all of these fields in F814W and F606W. For details on the full CANDELS survey, see Grogin et al. (2011ApJS..197...35G). In addition to the CANDELS observations, a portion of GOODS-S was also observed as a part of the WFC3 Early Release Science (ERS; Windhorst et al. 2011ApJS..193...27W) campaign in Y, J, and H. The CANDELS observations began in 2010 October and were completed in 2013 August. For this paper, we use mosaics at three different depths for comparison. (2 data files)

Functional genomics identifies therapeutic targets for MYC-driven cancer

MYC oncogene family members are broadly implicated in human cancers, yet are considered “undruggable” as they encode transcription factors. MYC also carries out essential functions in proliferative tissues, suggesting that its inhibition could cause severe side effects. We elected to identify synthetic lethal interactions with c-MYC overexpression (MYC-SL) in a collection of ∼3,300 druggable genes, using high-throughput siRNA screening. Of 49 genes selected for follow-up, 48 were confirmed by independent retesting and approximately one-third selectively induced accumulation of DNA damage, consistent with enrichment in DNA-repair genes by functional annotation. In addition, genes involved in histone acetylation and transcriptional elongation, such as TRRAP and BRD4, were identified, indicating that the screen revealed known MYC-associated pathways. For in vivo validation we selected CSNK1e, a kinase whose expression correlated with MYCN amplification in neuroblastoma (an established MYC-driven cancer). Using RNAi and available small-molecule inhibitors, we confirmed that inhibition of CSNK1e halted growth of MYCN-amplified neuroblastoma xenografts. CSNK1e had previously been implicated in the regulation of developmental pathways and circadian rhythms, whereas our data provide a previously unknown link with oncogenic MYC. Furthermore, expression of CSNK1e correlated with c-MYC and its transcriptional signature in other human cancers, indicating potential broad therapeutic implications of targeting CSNK1e function. In summary, through a functional genomics approach, pathways essential in the context of oncogenic MYC but not to normal cells were identified, thus revealing a rich therapeutic space linked to a previously “undruggable” oncogene