Abstract
Supernova remnants (SNRs), the products of stellar explosions, are powerful astrophysical laboratories, which allow us to study the physics of collisionless shocks, thanks to their bright ...electromagnetic emission. Blast wave shocks generated by supernovae (SNe) provide us with an observational window to study extreme conditions, characterized by high Mach (and Alfvénic Mach) numbers, together with powerful nonthermal processes. In collisionless shocks, temperature equilibration between different species may not be reached at the shock front. In this framework, different particle species may be heated at different temperatures (depending on their mass) in the post-shock medium of SNRs. SNRs are also characterized by broadband nonthermal emission stemming from the shock front as a result of nonthermal populations of leptons and hadrons. These particles, known as cosmic rays, are accelerated up to ultrarelativistic energies via diffusive shock acceleration. If SNRs lose a significant fraction of their ram energy to accelerate cosmic rays, the shock dynamics should be altered with respect to the adiabatic case. This shock modification should result in an increase in the total shock compression ratio with respect to the Rankine–Hugoniot value of 4. Here, I show that the combination of x-ray high resolution spectroscopy (to measure ion temperatures) and moderate resolution spectroscopy (for a detailed diagnostic of the post-shock density) can be exploited to study both the heating mechanism and the particle acceleration in collisionless shocks. I report on new results on the temperatures measured for different ion species in the remnant of the SN observed in 1987 in the Large Magellanic Cloud (SN 1987A). I also discuss evidence of shock modification recently obtained in the remnant of SN 1006 a. D., where the shock compression ratio increases significantly as the angle between the shock velocity and the ambient magnetic field is reduced.
ABSTRACT The remnants of core-collapse supernovae (SNe) have complex morphologies that may reflect asymmetries and structures developed during the progenitor SN explosion. Here we investigate how the ...morphology of the supernova remnant Cassiopeia A (Cas A) reflects the characteristics of the progenitor SN with the aim of deriving the energies and masses of the post-explosion anisotropies responsible for the observed spatial distribution of Fe and Si/S. We model the evolution of Cas A from the immediate aftermath of the progenitor SN to the three-dimensional interaction of the remnant with the surrounding medium. The post-explosion structure of the ejecta is described by small-scale clumping of material and larger-scale anisotropies. The hydrodynamic multi-species simulations consider an appropriate post-explosion isotopic composition of the ejecta. The observed average expansion rate and shock velocities can be well reproduced by models with ejecta mass Mej 4M and explosion energy ESN 2.3 × 1051 erg. The post-explosion anisotropies (pistons) reproduce the observed distributions of Fe and Si/S if they had a total mass of 0.25 M and a total kinetic energy of 1.5 × 1050 erg. The pistons produce a spatial inversion of ejecta layers at the epoch of Cas A, leading to the Si/S-rich ejecta physically interior to the Fe-rich ejecta. The pistons are also responsible for the development of the bright rings of Si/S-rich material which form at the intersection between the reverse shock and the material accumulated around the pistons during their propagation. Our result supports the idea that the bulk of asymmetries observed in Cas A are intrinsic to the explosion.
Mutations in DMD disrupt the reading frame, prevent dystrophin translation, and cause Duchenne muscular dystrophy (DMD). Here we describe a CRISPR/Cas9 platform applicable to 60% of DMD patient ...mutations. We applied the platform to DMD-derived hiPSCs where successful deletion and non-homologous end joining of up to 725 kb reframed the DMD gene. This is the largest CRISPR/Cas9-mediated deletion shown to date in DMD. Use of hiPSCs allowed evaluation of dystrophin in disease-relevant cell types. Cardiomyocytes and skeletal muscle myotubes derived from reframed hiPSC clonal lines had restored dystrophin protein. The internally deleted dystrophin was functional as demonstrated by improved membrane integrity and restoration of the dystrophin glycoprotein complex in vitro and in vivo. Furthermore, miR31 was reduced upon reframing, similar to observations in Becker muscular dystrophy. This work demonstrates the feasibility of using a single CRISPR pair to correct the reading frame for the majority of DMD patients.
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•Largest CRISPR/Cas9-mediated deletion of 725 kb of DMD•Reframed DMD hiPSCs differentiated to cardiac and skeletal muscle express dystrophin•Internally deleted dystrophin demonstrates functionality in vitro and in vivo•This single gRNA pair is therapeutically relevant to 60% of DMD mutations
Young et al. demonstrate restoration of the DMD reading frame by CRISPR/Cas9-mediated deletion of up to 725 kb in hiPSCs as a therapeutic strategy for 60% of Duchenne muscular dystrophy patients. The resulting internally deleted protein is shown to be functional in vitro and in vivo.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Context.
Massive stars end their lives in catastrophic supernova (SN) explosions. Key information on the explosion processes and on the progenitor stars can be extracted from observations of ...supernova remnants (SNRs), which are the outcome of SNe. Deciphering these observations, however, is challenging because of the complex morphology of SNRs.
Aims.
We aim to link the dynamical and radiative properties of the remnant of SN 1987A to the geometrical and physical characteristics of the parent aspherical SN explosion and to the internal structure of its progenitor star.
Methods.
We performed comprehensive three-dimensional hydrodynamic simulations which describe the long-term evolution of SN 1987A from the onset of the SN to the full-fledged remnant at the age of 50 years, accounting for the pre-SN structure of the progenitor star. The simulations include all physical processes relevant for the complex phases of SN evolution and for the interaction of the SNR with the highly inhomogeneous ambient environment around SN 1987A. Furthermore, the simulations follow the life cycle of elements from the synthesis in the progenitor star through the nuclear reaction network of the SN to the enrichment of the circumstellar medium as a result of the mixing of chemically homogeneous layers of ejecta. From the simulations, we synthesize observables that are to be compared with observations.
Results.
By comparing the model results with observations, we constrained the initial SN anisotropy causing Doppler shifts, observed in the emission lines of heavy elements from ejecta, and leading to the remnant evolution observed in the X-ray band in the last thirty years. In particular, we found that the high mixing of ejecta unveiled by high redshifts and broadenings of Fe II and
44
Ti lines require a highly asymmetric SN explosion channeling a significant fraction of energy along an axis that is almost lying in the plane of the central equatorial ring around SN 1987A, roughly along the line-of-sight, but with an offset of 40°, with the lobe propagating away from the observer slightly more energetic than the other. Furthermore, we found unambiguously that the observed distribution of ejecta and the dynamical and radiative properties of the SNR can be best reproduced if the structure of the progenitor star was that of a blue supergiant which had resulted from the merging of two massive stars.
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ABSTRACT
The detected polarized radio emission from the remnant of SN1987A opens the possibility to unveil the structure of the pre-supernova (pre-SN) magnetic field (MF) in the circumstellar medium. ...Properties derived from direct measurements would be of importance for understanding the progenitor stars and their MFs. As the first step to this goal, we adopted the hydrodynamic (HD) data from an elaborated three-dimensional (3D) numerical model of SN1987A. We have developed an approximate method for ‘reconstruction’ of 3D MF structure inside SN remnant on the 'HD background’. This method uses the distribution of the MF around the progenitor as the initial condition. With such a 3D magnetohydrodynamic model, we have synthesized the polarization maps for a number of SN1987A models and compared them to the observations. In this way, we have tested different initial configurations of the MF as well as a structure of the synchrotron emission in SN987A. We have recovered the observed polarization pattern and we have found that the radial component of the ambient pre-SN MF should be dominant on the length-scale of the present-day radius of SN1987A. The physical reasons for such a field are discussed.
Context.
Luminous blue variable stars (LBVs) are massive evolved stars that suffer sporadic and violent mass-loss events. They have been proposed as the progenitors of some core-collapse supernovae ...(SNe), but this idea is still debated because of a lack of strong evidence. As supernova remnants (SNRs) can carry in their morphology the fingerprints of the progenitor stars as well as of the inhomogeneous circumstellar medium (CSM) sculpted by the progenitors, the study of SNRs from LBVs could help to place core-collapse SNe in context with the evolution of massive stars.
Aims.
We investigate the physical, chemical, and morphological properties of the remnants of SNe originating from LBVs in order to search for signatures in the ejecta distribution and morphology of the remnants that could reveal the nature of the progenitors.
Methods.
As a template of LBVs, we considered the LBV candidate Gal 026.47+0.02. We selected a grid of models that describe the evolution of a massive star with properties consistent with those of Gal 026.47+0.02 and its final fate as a core-collapse SN. We developed a three-dimensional hydrodynamic model that follows the post-explosion evolution of the ejecta from the breakout of the shock wave at the stellar surface to the interaction of the SNR with a CSM characterized by two dense nested toroidal shells, parametrized in agreement with multi-wavelength observations of Gal 026.47+0.02.
Results.
Our models show a strong interaction of the blast wave with the CSM which determines an important slowdown of the expansion of the ejecta in the equatorial plane where the two shells lay, determining a high degree of asymmetry in the remnant. After ≈10 000 yr of evolution, the ejecta show an elongated shape forming a broad jet-like structure caused by the interaction with the shells and oriented along the axis of the toroidal shells. Models with high explosion energy show Fe-rich internal ejecta distributions surrounded by an elongated Si-rich structure with a more diffuse O-rich ejecta all around. Models with low explosion energy instead show a more homogeneous distribution of chemical elements with a very low presence of Fe-group elements.
Conclusions.
The geometry and density distribution of the CSM where a LBV star goes SN are fundamental in determining the properties of the resulting SNR. For all the LBV-like progenitors explored here, we found that the remnants show a common morphology, namely elongated ejecta with an internal jet-like structure, which reflects the inhomogeneous and dense pre-SN CSM surrounding the star.
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Antisense oligonucleotide (AON)‐mediated exon skipping is an emerging therapeutic for individuals with Duchenne muscular dystrophy (DMD). Skipping of exons adjacent to common exon deletions in DMD ...using AONs can produce in‐frame transcripts and functional protein. Targeted skipping of DMD exons 8, 44, 45, 50, 51, 52, 53, and 55 is predicted to benefit 47% of affected individuals. We observed a correlation between mutation subgroups and age at loss of ambulation in the Duchenne Registry, a large database of phenotypic and genetic data for DMD (N = 765). Males amenable to exon 44 (N = 74) and exon 8 skipping (N = 18) showed prolonged ambulation compared to other exon skip groups and nonsense mutations (P = 0.035 and P < 0.01, respectively). In particular, exon 45 deletions were associated with prolonged age at loss of ambulation relative to the rest of the exon 44 skip amenable cohort and other DMD mutations. Exon 3–7 deletions also showed prolonged ambulation relative to all other exon 8 skippable mutations. Cultured myotubes from DMD patients with deletions of exons 3–7 or exon 45 showed higher endogenous skipping than other mutations, providing a potential biological rationale for our observations. These results highlight the utility of aggregating phenotypic and genotypic data for rare pediatric diseases to reveal progression differences, identify potentially confounding factors, and probe molecular mechanisms that may affect disease severity.
Using patient data from the Duchenne Registry, DMD individuals were stratified into separate groups according to the predicted exon skip necessary to produce an in‐frame transcript. Delayed age at loss of ambulation was observed among DMD individuals amenable to skipping of exons 8 and 44, while exon 51 skippable individuals had earlier age of loss of ambulation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In the degenerative disease Duchenne muscular dystrophy, inflammatory cells enter muscles in response to repetitive muscle damage. Immune factors are required for muscle regeneration, but chronic ...inflammation creates a profibrotic milieu that exacerbates disease progression. Osteopontin (OPN) is an immunomodulator highly expressed in dystrophic muscles. Ablation of OPN correlates with reduced fibrosis and improved muscle strength as well as reduced natural killer T (NKT) cell counts. Here, we demonstrate that the improved dystrophic phenotype observed with OPN ablation does not result from reductions in NKT cells. OPN ablation skews macrophage polarization toward a pro-regenerative phenotype by reducing M1 and M2a and increasing M2c subsets. These changes are associated with increased expression of pro-regenerative factors insulin-like growth factor 1, leukemia inhibitory factor, and urokinase-type plasminogen activator. Furthermore, altered macrophage polarization correlated with increases in muscle weight and muscle fiber diameter, resulting in long-term improvements in muscle strength and function in mdx mice. These findings suggest that OPN ablation promotes muscle repair via macrophage secretion of pro-myogenic growth factors.
Context.
The Vela supernova remnant (SNR) shows several ejecta fragments (or shrapnel) protruding beyond the forward shock, which are most likely relics of anisotropies that developed during the ...supernova (SN) explosion. Recent studies have revealed high Si abundance in two shrapnel (shrapnel A and G), located in opposite directions with respect to the SNR center. This suggests the possible existence of a Si-rich jet-counterjet structure, similar to that observed in the SNR Cassiopea A.
Aims.
We analyzed an
XMM-Newton
observation of a bright clump, behind shrapnel G, which lies along the direction connecting shrapnel A and G. The aim is to study the physical and chemical properties of this clump to ascertain whether it is part of this putative jet-like structure.
Methods.
We produced background-corrected and adaptively-smoothed count-rate images and median photon energy maps, and performed a spatially resolved spectral analysis.
Results.
We identified two structures with different physical properties. The first one is remarkably elongated along the direction connecting shrapnel A and G. Its X-ray spectrum is much softer than that of the other two shrapnel, to the point of hindering the determination of the Si abundance; however, its physical and chemical properties are consistent with those of shrapnel A and shrapnel G. The second structure, running along the southeast-northwest direction, has a higher temperature and appears similar to a thin filament. By analyzing the ROSAT data, we have found that this filament is part of a very large and coherent structure that we identified in the western rim of the shell.
Conclusions.
We obtained a thorough description of the collimated, jet-like tail of shrapnel G in Vela SNR. In addition we discovered a coherent and very extended feature roughly perpendicular to the jet-like structure that we interpret as a signature of an earlier interaction of the remnant with the stellar wind of its progenitor star. The peculiar Ne/O ratio we found in the wind residual may be suggestive of a Wolf-Rayet progenitor for Vela SNR, though further analysis is required to address this point.
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Emerging and promising therapeutic interventions for Duchenne muscular dystrophy (DMD) are confounded by the challenges of quantifying dystrophin. Current approaches have poor precision, require ...large amounts of tissue, and are difficult to standardize. This paper presents an immuno-mass spectrometry imaging method using gadolinium (Gd)-labeled anti-dystrophin antibodies and laser ablation-inductively coupled plasma-mass spectrometry to simultaneously quantify and localize dystrophin in muscle sections. Gd is quantified as a proxy for the relative expression of dystrophin and was validated in murine and human skeletal muscle sections following k-means clustering segmentation, before application to DMD patients with different gene mutations where dystrophin expression was measured up to 100 µg kg
Gd. These results demonstrate that immuno-mass spectrometry imaging is a viable approach for pre-clinical to clinical research in DMD. It rapidly quantified relative dystrophin in single tissue sections, efficiently used valuable patient resources, and may provide information on drug efficacy for clinical translation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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