Systematic classification of non-coding RNAs by epigenomic similarity

BACKGROUND: Even though only 1.5% of the human genome is translated into proteins, recent reports indicate that most of it is transcribed into non-coding RNAs (ncRNAs), which are becoming the subject of increased scientific interest. We hypothesized that examining how different classes of ncRNAs co-localized with annotated epigenomic elements could help understand the functions, regulatory mechanisms, and relationships among ncRNA families. RESULTS: We examined 15 different ncRNA classes for statistically significant genomic co-localizations with cell type-specific chromatin segmentation states, transcription factor binding sites (TFBSs), and histone modification marks using GenomeRunner (http://www.genomerunner.org). P-values were obtained using a Chi-square test and corrected for multiple testing using the Benjamini-Hochberg procedure. We clustered and visualized the ncRNA classes by the strength of their statistical enrichments and depletions. We found piwi-interacting RNAs (piRNAs) to be depleted in regions containing activating histone modification marks, such as H3K4 mono-, di- and trimethylation, H3K27 acetylation, as well as certain TFBSs. piRNAs were further depleted in active promoters, weak transcription, and transcription elongation regions, and enriched in repressed and heterochromatic regions. Conversely, transfer RNAs (tRNAs) were depleted in heterochromatin regions and strongly enriched in regions containing activating H3K4 di- and trimethylation marks, H2az histone variant, and a variety of TFBSs. Interestingly, regions containing CTCF insulator protein binding sites were associated with tRNAs. tRNAs were also enriched in the active, weak and poised promoters and, surprisingly, in regions with repetitive/copy number variations. CONCLUSIONS: Searching for statistically significant associations between ncRNA classes and epigenomic elements permits detection of potential functional and/or regulatory relationships among ncRNA classes, and suggests cell type-specific biological roles of ncRNAs

Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria

Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such as through treatment with broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile and subsequent disease. Furthermore, failure of the gut microbiota to recover colonisation resistance can result in recurrence of infection. An unusual characteristic of C. difficile among gut bacteria is its ability to produce the bacteriostatic compound para-cresol (p-cresol) through fermentation of tyrosine. Here, we demonstrate that the ability of C. difficile to produce p-cresol in vitro provides a competitive advantage over gut bacteria including Escherichia coli, Klebsiella oxytoca and Bacteroides thetaiotaomicron. Metabolic profiling of competitive co-cultures revealed that acetate, alanine, butyrate, isobutyrate, p-cresol and p-hydroxyphenylacetate were the main metabolites responsible for differentiating the parent strain C. difficile (630Δerm) from a defined mutant deficient in p-cresol production. Moreover, we show that the p-cresol mutant displays a fitness defect in a mouse relapse model of C. difficile infection (CDI). Analysis of the microbiome from this mouse model of CDI demonstrates that colonisation by the p-cresol mutant results in a distinctly altered intestinal microbiota, and metabolic profile, with a greater representation of Gammaproteobacteria, including the Pseudomonales and Enterobacteriales. We demonstrate that Gammaproteobacteria are susceptible to exogenous p-cresol in vitro and that there is a clear divide between bacterial Phyla and their susceptibility to p-cresol. In general, Gram-negative species were relatively sensitive to p-cresol, whereas Gram-positive species were more tolerant. This study demonstrates that production of p-cresol by C. difficile has an effect on the viability of intestinal bacteria as well as the major metabolites produced in vitro. These observations are upheld in a mouse model of CDI, in which p-cresol production affects the biodiversity of gut microbiota and faecal metabolite profiles, suggesting that p-cresol production contributes to C. difficile survival and pathogenesis.Peer reviewedFinal Published versio

The Afterglow, Energetics and Host Galaxy of the Short-Hard Gamma-Ray Burst 051221a

We present detailed optical, X-ray and radio observations of the bright afterglow of the short gamma-ray burst 051221a obtained with Gemini, Swift/XRT, and the Very Large Array, as well as optical spectra from which we measure the redshift of the burst, z=0.5464. At this redshift the isotropic-equivalent prompt energy release was about 1.5 x 10^51 erg, and using the standard afterglow synchrotron model we find that the blastwave kinetic energy is similar, E_K,iso ~ 8.4 x 10^51 erg. An observed jet break at t ~ 5 days indicates that the opening angle is ~ 7 degrees and the total beaming-corrected energy is therefore ~ 2.5 x 10^49 erg, comparable to the values inferred for previous short GRBs. We further show that the burst experienced an episode of energy injection by a factor of 3.4 between t=1.4 and 3.4 hours, which was accompanied by reverse shock emission in the radio band. This result provides continued evidence that the central engines of short GRBs may be active significantly longer than the duration of the burst and/or produce a wide range of Lorentz factors. Finally, we show that the host galaxy of GRB051221a is actively forming stars at a rate of about 1.6 M_solar/yr, but at the same time exhibits evidence for an appreciable population of old stars (~ 1 Gyr) and near solar metallicity. The lack of bright supernova emission and the low circumburst density (n ~ 10^-3 cm^-3) continue to support the idea that short bursts are not related to the death of massive stars and are instead consistent with a compact object merger. Given that the total energy release is a factor of ~ 10 larger than the predicted yield for a neutrino annihilation mechanism, this suggests that magnetohydrodynamic processes may be required to power the burst.Comment: Final version (to appear in ApJ on 20 September 2006

RAPTOR observations of delayed explosive activity in the high-redshift gamma-ray burst GRB 060206

The RAPid Telescopes for Optical Response (RAPTOR) system at Los Alamos National Laboratory observed GRB 060206 starting 48.1 minutes after gamma-ray emission triggered the Burst Alert Telescope (BAT) on-board the Swift satellite. The afterglow light curve measured by RAPTOR shows a spectacular re-brightening by ~1 mag about 1 h after the trigger and peaks at R ~ 16.4 mag. Shortly after the onset of the explosive re-brightening the OT doubled its flux on a time-scale of about 4 minutes. The total R-band fluence received from GRB 060206 during this episode is 2.3e-9 erg/cm2. In the rest frame of the burst (z = 4.045) this yields an isotropic equivalent energy release of ~0.7e50 erg in just a narrow UV band 130 +/- 22 nm. We discuss the implications of RAPTOR observations for untriggered searches for fast optical transients and studies of GRB environments at high redshift.Comment: Submitted to ApJ Letter

The ROTSE-III Robotic Telescope System

The observation of a prompt optical flash from GRB990123 convincingly demonstrated the value of autonomous robotic telescope systems. Pursuing a program of rapid follow-up observations of gamma-ray bursts, the Robotic Optical Transient Search Experiment (ROTSE) has developed a next-generation instrument, ROTSE-III, that will continue the search for fast optical transients. The entire system was designed as an economical robotic facility to be installed at remote sites throughout the world. There are seven major system components: optics, optical tube assembly, CCD camera, telescope mount, enclosure, environmental sensing & protection and data acquisition. Each is described in turn in the hope that the techniques developed here will be useful in similar contexts elsewhere.Comment: 19 pages, including 4 figures. To be published in PASP in January, 2003. PASP Number IP02-11

The Dark Side of ROTSE-III Prompt GRB Observations

We present several cases of optical observations during gamma-ray bursts (GRBs) which resulted in prompt limits but no detection of optical emission. These limits constrain the prompt optical flux densities and the optical brightness relative to the gamma-ray emission. The derived constraints fall within the range of properties observed in GRBs with prompt optical detections, though at the faint end of optical/gamma flux ratios. The presently accessible prompt optical limits do not require a different set of intrinsic or environmental GRB properties, relative to the events with prompt optical detections.Comment: ApJ accepted. 20 pages in draft manuscript form, which includes 6 pages of tables and 2 figure

Prompt Optical Detection of GRB 050401 with ROTSE-IIIa

The ROTSE-IIIa telescope at Siding Spring Observatory, Australia, detected prompt optical emission from Swift GRB 050401. In this letter, we present observations of the early optical afterglow, first detected by the ROTSE-IIIa telescope 33 s after the start of gamma-ray emission, contemporaneous with the brightest peak of this emission. This GRB was neither exceptionally long nor bright. This is the first prompt optical detection of a GRB of typical duration and luminosity. We find that the early afterglow decay does not deviate significantly from the power-law decay observable at later times, and is uncorrelated with the prompt gamma-ray emission. We compare this detection with the other two GRBs with prompt observations, GRB 990123 and GRB 041219a. All three bursts exhibit quite different behavior at early times.Comment: 4 pages, 3 figures. Accepted for publication in ApJ Letter

Observations of the Optical Counterpart to XTE J1118+480 During Outburst by the ROTSE-I Telescope

The X-ray nova XTE J1118+480 exhibited two outbursts in the early part of 2000. As detected by the Rossi X-ray Timing Explorer (RXTE), the first outburst began in early January and the second began in early March. Routine imaging of the northern sky by the Robotic Optical Transient Search Experiment (ROTSE) shows the optical counterpart to XTE J1118+480 during both outbursts. These data include over 60 epochs from January to June 2000. A search of the ROTSE data archives reveal no previous optical outbursts of this source in selected data between April 1998 and January 2000. While the X-ray to optical flux ratio of XTE J1118+480 was low during both outbursts, we suggest that they were full X-ray novae and not mini-outbursts based on comparison with similar sources. The ROTSE measurements taken during the March 2000 outburst also indicate a rapid rise in the optical flux that preceded the X-ray emission measured by the RXTE by approximately 10 days. Using these results, we estimate a pre-outburst accretion disk inner truncation radius of 1.2 x 10^4 Schwarzschild radii.Comment: 9 pages, 1 table, 2 figure

The Troublesome Broadband Evolution of GRB 061126: Does a Grey Burst Imply Grey Dust?

We report on observations of a gamma-ray burst (GRB 061126) with an extremely bright (R ~ 12 mag at peak) early-time optical afterglow. The optical afterglow is already fading as a power law 22 seconds after the trigger, with no detectable prompt contribution in our first exposure, which was coincident with a large prompt-emission gamma-ray pulse. The optical--infrared photometric spectral energy distribution is an excellent fit to a power law, but it exhibits a moderate red-to-blue evolution in the spectral index at about 500 s after the burst. This color change is contemporaneous with a switch from a relatively fast decay to slower decay. The rapidly decaying early afterglow is broadly consistent with synchrotron emission from a reverse shock, but a bright forward-shock component predicted by the intermediate- to late-time X-ray observations under the assumptions of standard afterglow models is not observed. Indeed, despite its remarkable early-time brightness, this burst would qualify as a dark burst at later times on the basis of its nearly flat optical-to-X-ray spectral index. Our photometric spectral energy distribution provides no evidence of host-galaxy extinction, requiring either large quantities of grey dust in the host system (at redshift 1.1588 +/- 0.0006, based upon our late-time Keck spectroscopy) or separate physical origins for the X-ray and optical afterglows.Comment: Revised version submitted to ApJ. Contains significantly expanded discussion, an additional figure, and numerous other change