ADP-ribosylation is a posttranslational modification that exists in monomeric and polymeric forms. Whereas the writers (e.g. ARTD1/PARP1) and erasers (e.g. PARG, ARH3) of poly-ADP-ribosylation ...(PARylation) are relatively well described, the enzymes involved in mono-ADP-ribosylation (MARylation) have been less well investigated. While erasers for the MARylation of glutamate/aspartate and arginine have been identified, the respective enzymes with specificity for serine were missing. Here we report that, in vitro, ARH3 specifically binds and demodifies proteins and peptides that are MARylated. Molecular modeling and site-directed mutagenesis of ARH3 revealed that numerous residues are critical for both the mono- and the poly-ADP-ribosylhydrolase activity of ARH3. Notably, a mass spectrometric approach showed that ARH3-deficient mouse embryonic fibroblasts are characterized by a specific increase in serine-ADP-ribosylation in vivo under untreated conditions as well as following hydrogen peroxide stress. Together, our results establish ARH3 as a serine mono-ADP-ribosylhydrolase and as an important regulator of the basal and stress-induced ADP-ribosylome.
ABSTRACT We have combined observations of Galactic high-velocity H i from two surveys: a very sensitive survey from the Green Bank 140 ft Telescope with limited sky coverage, and the less sensitive ...but complete Galactic All Sky Survey from the 64 m Parkes Radio Telescope. The two surveys preferentially detect different forms of neutral gas due to their sensitivity. We adopt a machine learning approach to divide our data into two populations that separate across a range in column density: (1) a narrow line-width population typical of the majority of bright high velocity cloud components, and (2) a fainter, broad line-width population that aligns well with that of the population found in the Green Bank survey. We refer to these populations as dense and diffuse gas, respectively, and find that diffuse gas is typically located at the edges and in the tails of high velocity clouds, surrounding dense components in the core. A fit to the average spectrum of each type of gas in the Galactic All Sky Survey data reveals the dense population to have a typical line width of ∼20 km s−1 and brightness temperature of ∼0.3 K, while the diffuse population has a typical line width of ∼30 km s−1 and a brightness temperature of ∼0.2 K. Our results confirm that most surveys of high velocity gas in the Milky Way halo are missing the majority of the ubiquitous diffuse gas, and that this gas is likely to contribute at least as much mass as the dense gas.
Abstract
Many radio galaxies show the presence of dense and dusty gas near the active nucleus. This can be traced by both 21 cm H i absorption and soft X-ray absorption, offering new insight into the ...physical nature of the circumnuclear medium of these distant galaxies. To better understand this relationship, we investigate soft X-ray absorption as an indicator for the detection of associated H i absorption, as part of preparation for the First Large Absorption Survey in H i to be undertaken with the Australian Square Kilometre Array Pathfinder (ASKAP). We present the results of our pilot study using the Boolardy Engineering Test Array, a precursor to ASKAP, to search for new absorption detections in radio sources brighter than 1 Jy that also feature soft X-ray absorption. Based on this pilot survey, we detected H i absorption towards the radio source PKS 1657−298 at a redshift of z = 0.42. This source also features the highest X-ray absorption ratio of our pilot sample by a factor of 3, which is consistent with our general findings that X-ray absorption predicates the presence of dense neutral gas. By comparing the X-ray properties of active galactic nuclei with and without detection of H i absorption at radio wavelengths, we find that X-ray hardness ratio and H i absorption optical depth are correlated at a statistical significance of 4.71σ. We conclude by considering the impact of these findings on future radio and X-ray absorption studies.
ABSTRACT
We present early science results from the First Large Absorption Survey in H i (FLASH), a spectroscopically blind survey for 21-cm absorption lines in cold hydrogen (H i) gas at cosmological ...distances using the Australian Square Kilometre Array Pathfinder (ASKAP). We have searched for H i absorption towards 1253 radio sources in the GAMA 23 field, covering redshifts between z = 0.34 and 0.79 over a sky area of approximately 50 deg2. In a purely blind search, we did not obtain any detections of 21-cm absorbers above our reliability threshold. Assuming a fiducial value for the H i spin temperature of Tspin = 100 K and source covering fraction cf = 1, the total comoving absorption path-length sensitive to all Damped Lyman α Absorbers (DLAs; NH i ≥ 2 × 1020 cm−2) is ΔX = 6.6 ± 0.3 (Δz = 3.7 ± 0.2) and super-DLAs (NH i ≥ 2 × 1021 cm−2) is ΔX = 111 ± 6 (Δz= 63 ± 3). We estimate upper limits on the H i column density frequency distribution function that are consistent with measurements from prior surveys for redshifted optical DLAs, and nearby 21-cm emission and absorption. By cross-matching our sample of radio sources with optical spectroscopic identifications of galaxies in the GAMA 23 field, we were able to detect 21-cm absorption at z = 0.3562 towards NVSS J224500−343030, with a column density of $N_{\rm H\,\small{I}} = (1.2 \pm 0.1) \times 10^{20}\, (T_{\rm spin}/100\, \mathrm{K})$ cm−2. The absorber is associated with GAMA J22450.05−343031.7, a massive early-type galaxy at an impact parameter of 17 kpc with respect to the radio source and which may contain a massive (MH i ≳ 3 × 109 M⊙) gas disc. Such gas-rich early types are rare, but have been detected in the nearby Universe.
ABSTRACT
Obscuration of quasars by accreted gas and dust, or dusty intervening galaxies, can cause active galactic nuclei (AGN) to be missed in optically selected surveys. Radio observations can ...overcome this dust bias. In particular, radio surveys searching for H i absorption inform us on how the AGN can impact on the cold neutral gas medium within the host galaxy, or the population of intervening galaxies through the observed line of sight gas kinematics. We present the results of an H i absorption line survey at 0.4 < z < 1 towards 34 obscured quasars with the Australian SKA Pathfinder (ASKAP) commissioning array. We detect three H i absorption lines, with one of these systems previously unknown. Through optical follow-up for two sources, we find that in all detections the H i gas is associated with the AGN, and hence that these AGN are obscured by material within their host galaxies. Most of our sample are compact, and in addition, are either gigahertz peaked spectrum (GPS), or steep spectrum (CSS) sources, both thought to represent young or recently re-triggered radio AGN. The radio spectral energy distribution classifications for our sample agree with galaxy evolution models in which the obscured AGN has only recently become active. Our associated H i detection rate for GPS and compact SS sources matches those of other surveys towards such sources. We also find shallow and asymmetric H i absorption features, which agrees with previous findings that the cold neutral medium in compact radio galaxies is typically kinematically disturbed by the AGN.
To synthesise exercise therapy intervention data investigating patient rating outcomes for the management of tendinopathy.
A systematic review and meta-analysis of randomized controlled trials ...investigating exercise therapy interventions and reporting patient rating outcomes.
Any setting in any country listed as very high on the human development index.
People with a diagnosis of any tendinopathy of any severity or duration.
Exercise therapy for the management of tendinopathy comprising five different therapy classes: 1) resistance; 2) plyometric; 3) vibration; 4) flexibility, and 5) movement pattern retraining modalities, were considered for inclusion.
Outcomes measuring patient rating of condition, including patient satisfaction and Global Rating of Change (GROC).
From a total of 124 exercise therapy studies, 34 (Achilles: 41%, rotator cuff: 32%, patellar: 15%, elbow: 9% and gluteal: 3%) provided sufficient information to be meta-analysed. The data were obtained across 48 treatment arms and 1246 participants. The pooled estimate for proportion of satisfaction was 0.63 95%CrI: 0.53–0.73, and the pooled estimate for percentage of maximum GROC was 53 95%CrI: 38–69%. The proportion of patients reporting positive satisfaction and perception of change increased with longer follow-up periods from treatment onset.
Patient satisfaction and GROC appear similar and are ranked moderately high demonstrating that patients generally perceive exercise therapies positively. Further research including greater consistency in measurement tools is required to explore and where possible, identify patient- and exercise-related moderating factors that can be used to improve person-centred care.
PROSPERO ID=CRD42020168187
•Patient rating of condition is one of the least measured core outcome domains in studies investigating exercise therapy.•Patients are generally satisfied and report positive perceptions of change with exercise therapy for the management of tendinopathies.
Super massive black holes at the centres of galaxies can cycle through periods of activity and quiescence. Characterising the duty cycle of active galactic nuclei (AGN) is crucial for understanding ...the impact of the energy they release on the host galaxy. For radio AGN, this can be done by identifying dying (remnant) and restarted radio galaxies from their radio spectral properties. Using the combination of the images at 1400 MHz produced by Apertif, the new phased-array feed receiver installed on the Westerbork Synthesis Radio Telescope, and images at 150 MHz provided by LOFAR, we have derived resolved spectral index images (at a resolution of ~15 arcsec) for all the sources within an approximately 6 deg
2
area of the Lockman Hole region. In this way, we were able to select 15 extended radio sources with emission (partly or entirely) characterised by extremely steep spectral indices (steeper than 1.2). These objects represent cases of radio sources in the remnant or the restarted phases of their life cycle. Our findings confirm that these objects are not as rare as previously thought, suggesting a relatively fast cycle. They also show a variety of properties that can be relevant for modelling the evolution of radio galaxies. For example, the restarted activity can occur while the remnant structure from a previous phase of activity is still visible. This provides constraints on the duration of the “off” (dying) phase. In extended remnants with ultra-steep spectra at low frequencies, the activity likely stopped a few hundred megayears ago, and they correspond to the older tail of the age distribution of radio galaxies, in agreement with the results of simulations of radio source evolution. We find remnant radio sources with a variety of structures (from double-lobed to amorphous), possibly suggesting different types of progenitors. The present work sets the stage for exploiting the powerful tool of low-frequency spectral index studies of extended sources by taking advantage of the large areas common to the LOFAR and the Apertif surveys.
Tens-of-millions of women every year test positive for human papillomavirus (HPV) at routine cervical screening. We performed a mixed-methods systematic review using a results-based convergent design ...to provide the first comprehensive overview of emotional response to testing positive for HPV (HPV+). We mapped our findings using the cognitive behavioural framework. Six electronic databases were searched from inception to 09-Nov-2019 and 33 papers were included. Random-effects meta-analyses revealed that HPV+ women with abnormal or normal cytology displayed higher short-term anxiety than those with normal results (MD on State-Trait Anxiety Inventory = 7.6, 95% CI: 4.59-10.60 and MD = 6.33, CI: 1.31-11.35, respectively); there were no long-term differences. Psychological distress (general/sexual/test-specific) was higher in HPV+ women with abnormal cytology in the short-term and long-term (SMD = 0.68, CI: 0.32-1.03 and SMD = 0.42, CI: 0.05-0.80, respectively). Testing HPV+ was also related to disgust/shame, surprise and fear about cancer. Broadly, adverse response related to eight cognitive constructs (low control, confusion, cancer-related concerns, relationship concerns, sexual concerns, uncertainty, stigma, low trust) and six behavioural constructs (relationship problems, social impact, non-disclosure of results, idiosyncratic prevention, indirect clinical interaction, changes to sexual practice). Almost exclusive use of observational and qualitative designs limited inferences of causality and conclusions regarding clinical significance.
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