Covalent intermediate in the catalytic mechanism of the radical S-adenosyl-L-methionine methyl synthase RlmN trapped by mutagenesis.

The posttranscriptional modification of ribosomal RNA (rRNA) modulates ribosomal function and confers resistance to antibiotics targeted to the ribosome. The radical S-adenosyl-L-methionine (SAM) methyl synthases, RlmN and Cfr, both methylate A2503 within the peptidyl transferase center of prokaryotic ribosomes, yielding 2-methyl- and 8-methyl-adenosine, respectively. The C2 and C8 positions of adenosine are unusual methylation substrates due to their electrophilicity. To accomplish this reaction, RlmN and Cfr use a shared radical-mediated mechanism. In addition to the radical SAM CX(3)CX(2)C motif, both RlmN and Cfr contain two conserved cysteine residues required for in vivo function, putatively to form (cysteine 355 in RlmN) and resolve (cysteine 118 in RlmN) a covalent intermediate needed to achieve this challenging transformation. Currently, there is no direct evidence for this proposed covalent intermediate. We have further investigated the roles of these conserved cysteines in the mechanism of RlmN. Cysteine 118 mutants of RlmN are unable to resolve the covalent intermediate, either in vivo or in vitro, enabling us to isolate and characterize this intermediate. Additionally, tandem mass spectrometric analyses of mutant RlmN reveal a methylene-linked adenosine modification at cysteine 355. Employing deuterium-labeled SAM and RNA substrates in vitro has allowed us to further clarify the mechanism of formation of this intermediate. Together, these experiments provide compelling evidence for the formation of a covalent intermediate species between RlmN and its rRNA substrate and well as the roles of the conserved cysteine residues in catalysis

The clustering of X-ray AGN at 0.5 < z < 4.5 : host galaxies dictate dark matter halo mass

We present evidence that active galactic nuclei (AGN) do not reside in 'special' environments, but instead show large-scale clustering determined by the properties of their host galaxies. Our study is based on an angular cross-correlation analysis applied to X-ray selected AGN in the COSMOS and UDS fields, spanning redshifts from z ∼ 4.5 to z ∼ 0.5. Consistent with previous studies, we find that AGN at all epochs are on average hosted by galaxies in dark matter haloes of 1012-1013 M⊙, intermediate between star-forming and passive galaxies. We find, however, that the same clustering signal can be produced by inactive (I.e. non-AGN) galaxies closely matched to the AGN in spectral class, stellar mass, and redshift. We therefore argue that the inferred bias for AGN lies in between the star-forming and passive galaxy populations because AGN host galaxies are comprised of a mixture of the two populations. Although AGN hosted by higher mass galaxies are more clustered than lower mass galaxies, this stellar mass dependence disappears when passive host galaxies are removed. The strength of clustering is also largely independent of AGN X-ray luminosity. We conclude that the most important property that determines the clustering in a given AGN population is the fraction of passive host galaxies. We also infer that AGN luminosity is likely not driven by environmental triggering, and further hypothesize that AGN may be a stochastic phenomenon without a strong dependence onenvironment.Publisher PDFPeer reviewe

Massive post-starburst galaxies at z > 1 are compact proto-spheroids

We investigate the relationship between the quenching of star formation and the structural transformation of massive galaxies, using a large sample of photometrically-selected poststarburst galaxies in the UKIDSS UDS field. We find that post-starburst galaxies at highredshift (z > 1) show high Sérsic indices, significantly higher than those of active star-forming galaxies, but with a distribution that is indistinguishable from the old quiescent population. We conclude that the morphological transformation occurs before (or during) the quenching of star formation. Recently quenched galaxies are also the most compact; we find evidence that massive post-starburst galaxies (M_ > 1010:5 M_) at high redshift (z > 1) are on average smaller than comparable quiescent galaxies at the same epoch. Our findings are consistent with a scenario in which massive passive galaxies are formed from three distinct phases: (1) gas-rich dissipative collapse to very high densities, forming the proto-spheroid; (2) rapid quenching of star formation, to create the “red nugget” with post-starburst features; (3) a gradual growth in size as the population ages, perhaps as a result of minor mergers

The identification of post-starburst galaxies at z∼1 using multiwavelength photometry: a spectroscopic verification

Despite decades of study, we still do not fully understand why some massive galaxies abruptly switch off their star formation in the early Universe, and what causes their rapid transition to the red sequence. Post-starburst galaxies provide a rare opportunity to study this transition phase, but few have currently been spectroscopically identified at high redshift (z > 1). In this paper, we present the spectroscopic verification of a new photometric technique to identify post-starbursts in high-redshift surveys. The method classifies the broad-band optical–nearinfrared spectral energy distributions (SEDs) of galaxies using three spectral shape parameters (supercolours), derived from a principal component analysis of model SEDs. When applied to the multiwavelength photometric data in the UKIDSS Ultra Deep Survey, this technique identified over 900 candidate post-starbursts at redshifts 0.5 5 angstrem) and Balmer break, characteristic of post-starburst galaxies.We conclude that photometric methods can be used to select large samples of recently-quenched galaxies in the distant Universe

The structure of post-starburst galaxies at 0.5 < z < 2: evidence for two distinct quenching routes at different epochs

We present an analysis of the structure of post-starburst (PSB) galaxies in the redshift range 0.5 1), PSBs are typically massive (M* > 10^10 Msun), very compact and exhibit high Sérsic indices, with structures that differ significantly from their star-forming progenitors but are similar to massive passive galaxies. In contrast, at lower redshift (0.5 1 have been recently quenched during a major disruptive event (e.g. merger or protogalactic collapse) that formed a compact remnant, while at z < 1 an alternative less disruptive process is primarily responsible. Our results suggest that high-z PSBs are an intrinsically different population to those at lower redshifts, and indicate different quenching routes are active at different epochs

Absence of Evidence Is Not Evidence of Absence: The Color-Density Relation at Fixed Stellar Mass Persists to z ~ 1

We use data drawn from the DEEP2 Galaxy Redshift Survey to investigate the relationship between local galaxy density, stellar mass, and rest-frame galaxy color. At z ~ 0.9, we find that the shape of the stellar mass function at the high-mass (log (M*/Msun) > 10.1) end depends on the local environment, with high-density regions favoring more massive systems. Accounting for this stellar mass-environment relation (i.e., working at fixed stellar mass), we find a significant color-density relation for galaxies with 10.6 < log(M*/Msun) < 11.1 and 0.75 < z < 0.95. This result is shown to be robust to variations in the sample selection and to extend to even lower masses (down to log(M*/Msun) ~ 10.4). We conclude by discussing our results in comparison to recent works in the literature, which report no significant correlation between galaxy properties and environment at fixed stellar mass for the same redshift and stellar mass domain. The non-detection of environmental dependence found in other data sets is largely attributable to their smaller samples size and lower sampling density, as well as systematic effects such as inaccurate redshifts and biased analysis techniques. Ultimately, our results based on DEEP2 data illustrate that the evolutionary state of a galaxy at z ~ 1 is not exclusively determined by the stellar mass of the galaxy. Instead, we show that local environment appears to play a distinct role in the transformation of galaxy properties at z > 1.Comment: 10 pages, 5 Figures; Accepted for publication in MNRA

Compact star-forming galaxies preferentially quenched to become PSBs in z < 1 clusters

MS acknowledges support from IAC and STFC. VW acknowledges support from the European Research Council Starting grant (SEDmorph, P.I. V. Wild).We analyse the structure of galaxies with high specific star formation rate (SSFR) in cluster and field environments in the redshift range 0.5 < z < 1.0. Recent studies have shown that these galaxies are strongly depleted in dense environments due to rapid environmental quenching, giving rise to post-starburst galaxies (PSBs). We use effective radii and Sérsic indices as tracers of galaxy structure, determined using imaging from the UKIDSS Ultra Deep Survey (UDS). We find that the high-SSFR galaxies that survive into the cluster environment have, on average, larger effective radii than those in the field. We suggest that this trend is likely to be driven by the most compact star-forming galaxies being preferentially quenched in dense environments. We also show that the PSBs in clusters have stellar masses and effective radii that are similar to the missing compact star-forming population, suggesting that these PSBs are the result of size-dependent quenching. We propose that both strong stellar feedback and the stripping of the extended halo act together to preferentially and rapidly quench the compact and low-mass star-forming systems in clusters to produce PSBs. We test this scenario using the stacked spectra of 124 high-SSFR galaxies, showing that more compact galaxies are more likely to host outflows. We conclude that a combination of environmental and secular processes is the most likely explanation for the appearance of PSBs in galaxy clusters.PostprintPeer reviewe

Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19:phase 3 randomised controlled trial (CORONAVIT)

OBJECTIVE: To determine the effect of population level implementation of a test-and-treat approach to correction of suboptimal vitamin D status (25-hydroxyvitamin D (25(OH)D) <75 nmol/L) on risk of all cause acute respiratory tract infection and covid 19. DESIGN: Phase 3 open label randomised controlled trial. SETTING: United Kingdom. PARTICIPANTS: 6200 people aged ≥16 years who were not taking vitamin D supplements at baseline. INTERVENTIONS: Offer of a postal finger prick test of blood 25(OH)D concentration with provision of a six month supply of lower dose vitamin D (800 IU/day, n=1550) or higher dose vitamin D (3200 IU/day, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, compared with no offer of testing or supplementation (n=3100). Follow-up was for six months. MAIN OUTCOME MEASURES: The primary outcome was the proportion of participants with at least one swab test or doctor confirmed acute respiratory tract infection of any cause. A secondary outcome was the proportion of participants with swab test confirmed covid-19. Logistic regression was used to calculate odds ratios and associated 95% confidence intervals. The primary analysis was conducted by intention to treat. RESULTS: Of 3100 participants offered a vitamin D test, 2958 (95.4%) accepted and 2674 (86.3%) had 25(OH)D concentrations <75 nmol/L and received vitamin D supplements (n=1328 lower dose, n=1346 higher dose). Compared with 136/2949 (4.6%) participants in the no offer group, at least one acute respiratory tract infection of any cause occurred in 87/1515 (5.7%) in the lower dose group (odds ratio 1.26, 95% confidence interval 0.96 to 1.66) and 76/1515 (5.0%) in the higher dose group (1.09, 0.82 to 1.46). Compared with 78/2949 (2.6%) participants in the no offer group, 55/1515 (3.6%) developed covid-19 in the lower dose group (1.39, 0.98 to 1.97) and 45/1515 (3.0%) in the higher dose group (1.13, 0.78 to 1.63). CONCLUSIONS: Among people aged 16 years and older with a high baseline prevalence of suboptimal vitamin D status, implementation of a population level test-and-treat approach to vitamin D supplementation was not associated with a reduction in risk of all cause acute respiratory tract infection or covid-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04579640

OMEGA - OSIRIS Mapping of Emission-line Galaxies in A901/2 - II. Environmental influence on integrated star formation properties and AGN activity

We present a study of the star formation and AGN activity for galaxies in CP 15051 the Abell 901/2 multicluster system at z ∼ 0.167 as part of the OSIRIS Mapping of Emission-line Galaxies in A901/2 (OMEGA) survey. Using Tuneable Filter data obtained with the OSIRIS instrument at the Gran Telescopio Canarias, we produce spectra covering the Hα and [N II] spectral lines for more than 400 galaxies. Using optical emission-line diagnostics, we identify a significant number of galaxies hosting AGN, which tend to have high masses and a broad range of morphologies.Moreover, within the environmental densities probed by our study, we find no environmental dependence on the fraction of galaxies hosting AGN. The analysis of the integrated Hα emission shows that the specific star formation rates of a majority of the cluster galaxies are below the field values for a given stellar mass.We interpret this result as evidence for a slow decrease in the star formation activity of star-forming galaxies as they fall into higher density regions, contrary to some previous studies that suggested a rapid truncation of star formation.We find that most of the intermediate- and high-mass spiral galaxies go through a phase in which their star formation is suppressed but still retain significant star formation activity. During this phase, these galaxies tend to retain their spiral morphology while their colours become redder. The presence of this type of galaxies in high-density regions indicates that the physical mechanism responsible for suppressing star formation affects mainly the gas component of the galaxies, suggesting that ram-pressure stripping or starvation is potentially responsible.We acknowledge financial support from STFC. This work has made use of The University of Nottingham HPC facility, ‘Minerva’. BRP acknowledges financial support from the Spanish Ministry of Economy and Competitiveness through the Plan Nacional de Astronom´ıa y Astrof´ısica grant AYA2012-032295. ACS acknowledges funding from a CNPq, BJT-A fellowship (400857/2014-6). SPB and MEG gratefully acknowledge the receipt of an STFC Advanced Fellowship. AB is funded by the Austrian Science Foundation FWF (grant P23946-N16)

Prostaglandin E2 affects T cell responses through modulation of CD46 expression

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