Cytochrome oxidase subunit VI of Trypanosoma brucei is imported without a cleaved presequence and is developmentally regulated at both RNA and protein levels

Mitochondrial respiration in the African trypanosome undergoes dramatic developmental stage regulation. This requires co-ordinated control of components encoded by both the nuclear genome and the kinetoplast, the unusual mitochondrial genome of these parasites. As a model for understanding the co-ordination of these genomes, we have examined the regulation and mitochondrial import of a nuclear-encoded component of the cytochrome oxidase complex, cytochrome oxidase subunit VI (COXVI). By generating transgenic trypanosomes expressing intact or mutant forms of this protein, we demonstrate that COXVI is not imported using a conventional cleaved presequence and show that sequences at the N-terminus of the protein are necessary for correct mitochondrial sorting. Analyses of endogenous and transgenic COXVI mRNA and protein expression in parasites undergoing developmental stage differentiation demonstrates a temporal order of control involving regulation in the abundance of, first, mRNA and then protein. This represents the first dissection of the regulation and import of a nuclear-encoded protein into the cytochrome oxidase complex in these organisms, which were among the earliest eukaryotes to possess a mitochondrion

The detection of cluster magnetic fields via radio source depolarisation

It has been well established that galaxy clusters have magnetic fields. The exact properties and origin of these magnetic fields are still uncertain even though these fields play a key role in many astrophysical processes. Various attempts have been made to derive the magnetic field strength and structure of nearby galaxy clusters using Faraday rotation of extended cluster radio sources. This approach needs to make various assumptions that could be circumvented when using background radio sources. However, because the number of polarised radio sources behind clusters is low, at the moment such a study can only be done statistically. In this paper, we investigate the depolarisation of radio sources inside and behind clusters in a sample of 124 massive clusters at $z<0.35$ observed with the Karl G. Jansky Very Large Array. We detect a clear depolarisation trend with the cluster impact parameter, with sources at smaller projected distances to the cluster centre showing more depolarisation. By combining the radio observations with ancillary X-ray data from Chandra, we compare the observed depolarisation with expectations from cluster magnetic field models using individual cluster density profiles. The best-fitting models have a central magnetic field strength of $5-10\,\mu$G with power-law indices between $n=1$ and $n=4$. We find no strong difference in the depolarisation trend between sources embedded in clusters and background sources located at similar projected radii, although the central region of clusters is still poorly probed by background sources. We also examine the depolarisation trend as a function of cluster properties such as the dynamical state, mass, and redshift. Our findings show that the statistical depolarisation of radio sources is a good probe of cluster magnetic field parameters. [abridged]Comment: Replaced with Published version (A&A). 32 pages, 34 figure

Immune checkpoint inhibitor-associated myocarditis:Case reports and a review of the literature

Immune checkpoint inhibitors (ICIs) are increasingly recognised to effectuate long-lasting therapeutic responses in solid tumours. However, ICI therapy can also result in various immune-related adverse events, such as ICI-associated myocarditis, a rare but serious complication. The clinical spectrum is wide and includes asymptomatic patients and patients with fulminant heart failure, making it challenging to diagnose this condition. Furthermore, the optimal diagnostic algorithm and treatment of ICI-associated myocarditis is unknown. In this review, we describe two cases on both ends of the spectrum and discuss the challenges in recognising, diagnosing and treating ICI-associated myocarditis

A MeerKAT-meets-LOFAR study of Abell 1413: a moderately disturbed non-cool-core cluster hosting a ∼500\sim 500 kpc 'mini'-halo

Many relaxed cool-core clusters host diffuse radio emission on scales of hundreds of kiloparsecs: mini-haloes. However, the mechanism responsible for generating them, as well as their connection with central active galactic nuclei, is elusive and many questions related to their physical properties and origins remain unanswered. This paper presents new radio observations of the galaxy cluster Abell 1413 performed with MeerKAT (L-band; 872 to 1712 MHz) and LOFAR HBA (120 to 168 MHz) as part of a statistical and homogeneous census of mini-haloes. Abell 1413 is unique among mini-halo clusters as it is a moderately-disturbed non-cool-core cluster. Our study reveals an asymmetric mini-halo up to 584 kpc in size at 1283 MHz, twice as large as first reported at similar frequencies. The spectral index is flatter than previously reported, with an integrated value of $\alpha = -1.01 \pm 0.06$, shows significant spatial variation, and a tentative radial steepening. We studied the point-to-point X-ray/radio surface brightness correlation to investigate the thermal/non-thermal connection: our results show a strong connection between these components, with a super-linear slope of $b = 1.63 \pm 0.10$ at 1283 MHz and $b = 1.20 \pm 0.12$ at 145 MHz. We also explore the X-ray surface brightness/radio spectral index correlation, finding a slope of $b = 0.59 \pm 0.11$. Both investigations support the evidence of spectral steepening. Finally, in the context of understanding the particle acceleration mechanism, we present a simple theoretical model which demonstrates that hybrid scenarios - secondary electrons (re-)accelerated by turbulence - reproduce a super-linear correlation slope.Comment: 19 pages, 11 figures, 4 tables. Accepted for publication in MNRA

A giant radio bridge connecting two clusters in Abell 1758

Collisions between galaxy clusters dissipate enormous amounts of energy in the intra-cluster medium (ICM) through turbulence and shocks. In the process, Mpc-scale diffuse synchrotron emission in form of radio halos and relics can form. However, little is known about the very early phase of the collision. We used deep radio observations from 53 MHz to 1.5 GHz to study the pre-merging galaxy clusters A1758N and A1758S that are $\sim2$ Mpc apart. We confirm the presence of a giant bridge of radio emission connecting the two systems that was reported only tentatively in our earlier work. This is the second large-scale radio bridge observed to date in a cluster pair. The bridge is clearly visible in the LOFAR image at 144 MHz and tentatively detected at 53 MHz. Its mean radio emissivity is more than one order of magnitude lower than that of the radio halos in A1758N and A1758S. Interestingly, the radio and X-ray emissions of the bridge are correlated. Our results indicate that non-thermal phenomena in the ICM can be generated also in the region of compressed gas in-between infalling systems.Comment: 6 pages, 4 figures, 1 table. Accepted for publication in MNRAS Letter

A giant radio bridge connecting two galaxy clusters in Abell 1758

Collisions between galaxy clusters dissipate enormous amounts of energy in the intracluster medium (ICM) through turbulence and shocks. In the process, Mpc-scale diffuse synchrotron emission in form of radio haloes and relics can form. However, little is known about the very early phase of the collision. We used deep radio observations from 53 MHz to 1.5 GHz to study the pre-merging galaxy clusters A1758N and A1758S that are ∼2 Mpc apart. We confirm the presence of a giant bridge of radio emission connecting the two systems that was reported only tentatively in our earlier work. This is the second large-scale radio bridge observed to date in a cluster pair. The bridge is clearly visible in the LOFAR image at 144 MHz and tentatively detected at 53 MHz. Its mean radio emissivity is more than one order of magnitude lower than that of the radio haloes in A1758N and A1758S. Interestingly, the radio and X-ray emissions of the bridge are correlated. Our results indicate that non-thermal phenomena in the ICM can be generated also in the region of compressed gas in-between infalling systems

Diffuse Radio Emission from Galaxy Clusters in the LOFAR Two-metre Sky Survey Deep Fields

This paper is part of the 1st data release of the LoTSS Deep Fields. Re-submitted paper (reply to referee). © 2020 The European Southern Observatory (ESO)Low-frequency radio observations are revealing an increasing number of diffuse synchrotron sources from galaxy clusters, dominantly in the form of radio halos or radio relics. The existence of this diffuse synchrotron emission indicates the presence of relativistic particles and magnetic fields. It is still an open question what mechanisms exactly are responsible for the population of relativistic electrons driving this synchrotron emission. The LOFAR Two-metre Sky Survey Deep Fields offer a unique view of this problem. Reaching noise levels below 30 $\mu$Jy/beam, these are the deepest images made at the low frequency of 144 MHz. This paper presents a search for diffuse emission in galaxy clusters in the first data release of the LOFAR Deep Fields. We detect a new high-redshift radio halo with a flux density of $8.9 \pm 1.0$ mJy and corresponding luminosity of $P_{144\mathrm{MHz}}=(3.6 \pm 0.6)\times10^{25}$ W Hz$^{-1}$ in an X-ray detected cluster at $z=0.77$ with a mass estimate of $M_{500} = 3.3_{-1.7}^{+1.1} \times 10^{14} M_\odot.$ Deep upper limits are placed on clusters with non-detections. We compare the results to the correlation between halo luminosity and cluster mass derived for radio halos found in the literature. This study is one of few to find diffuse emission in low mass ($M_{500} <5\times10^{14} M_\odot$) systems and shows that deep low-frequency observations of galaxy clusters are fundamental for opening up a new part of parameter space in the study of non-thermal phenomena in galaxy clusters.Peer reviewe

Deep Low-frequency Radio Observations of A2256. I. the Filamentary Radio Relic

We present deep and high-fidelity images of the merging galaxy cluster A2256 at low frequencies using the upgraded Giant Metrewave Radio Telescope (uGMRT) and LOw-Frequency ARray (LOFAR). This cluster hosts one of the most prominent known relics with a remarkably spectacular network of filamentary substructures. The new uGMRT (300-850 MHz) and LOFAR (120-169 MHz) observations, combined with the archival Karl G. Jansky Very Large Array (VLA; 1-4 GHz) data, allowed us to carry out the first spatially resolved spectral analysis of the exceptional relic emission down to 6″ resolution over a broad range of frequencies. Our new sensitive radio images confirm the presence of complex filaments of magnetized relativistic plasma also at low frequencies. We find that the integrated spectrum of the relic is consistent with a single power law, without any sign of spectral steepening, at least below 3 GHz. Unlike previous claims, the relic shows an integrated spectral index of -1.07 ± 0.02 between 144 MHz and 3 GHz, which is consistent with the (quasi)stationary shock approximation. The spatially resolved spectral analysis suggests that the relic surface very likely traces the complex shock front, with a broad distribution of Mach numbers propagating through a turbulent and dynamically active intracluster medium. Our results show that the northern part of the relic is seen edge-on and the southern part close to face-on. We suggest that the complex filaments are regions where higher Mach numbers dominate the (re)acceleration of electrons that are responsible for the observed radio emission

Efficacy of alpha-Blockers on Hemodynamic Control during Pheochromocytoma Resection:A Randomized Controlled Trial

CONTEXT: Pretreatment with α-adrenergic receptor blockers is recommended to prevent hemodynamic instability during resection of a pheochromocytoma or sympathetic paraganglioma (PPGL). OBJECTIVE: To determine which type of α-adrenergic receptor blocker provides the best efficacy. DESIGN: Randomized controlled open-label trial (PRESCRIPT; ClinicalTrials.gov NCT01379898). SETTING: Multicenter study including 9 centers in The Netherlands. PATIENTS: 134 patients with non-metastatic PPGL. INTERVENTION: phenoxybenzamine or doxazosin starting 2-3 weeks before surgery using a blood pressure targeted titration schedule. Intraoperative hemodynamic management was standardized. MAIN OUTCOME MEASURES: Primary efficacy endpoint was the cumulative intraoperative time outside the blood pressure target range (i.e., SBP >160 mmHg or MAP <60 mmHg) expressed as a percentage of total surgical procedure time. Secondary efficacy endpoint was the value on a hemodynamic instability score. RESULTS: Median cumulative time outside blood pressure targets was 11.1% [IQR: 4.3-20.6] in the phenoxybenzamine group compared to 12.2% [5.3-20.2] in the doxazosin group (P=0.75, r=0.03). The hemodynamic instability score was 38.0 [28.8-58.0] and 50.0 [35.3-63.8] in the phenoxybenzamine and doxazosin group, respectively (P=0.02, r=0.20). The 30-day cardiovascular complication rate was 8.8% and 6.9% in the phenoxybenzamine and doxazosin group, respectively (P=0.68). There was no mortality after 30 days. CONCLUSIONS: The duration of blood pressure outside the target range during resection of a PPGL was not different after preoperative treatment with either phenoxybenzamine or doxazosin. Phenoxybenzamine was more effective in preventing intraoperative hemodynamic instability, but it could not be established whether this was associated with a better clinical outcome