Cartilage defects repair poorly. Recent genetic studies suggest that WNT3a may contribute to cartilage regeneration, however the dense, avascular cartilage extracellular matrix limits its penetration ...and signalling to chondrocytes. Extracellular vesicles actively penetrate intact cartilage. This study investigates the effect of delivering WNT3a into large cartilage defects in vivo using exosomes as a delivery vehicle. Exosomes were purified by ultracentrifugation from conditioned medium of either L‐cells overexpressing WNT3a or control un‐transduced L‐cells, and characterized by electron microscopy, nanoparticle tracking analysis and marker profiling. WNT3a loaded on exosomes was quantified by western blotting and functionally characterized in vitro using the SUPER8TOPFlash reporter assay and other established readouts including proliferation and proteoglycan content. In vivo pathway activation was assessed using TCF/Lef:H2B‐GFP reporter mice. Wnt3a loaded exosomes were injected into the knees of mice, in which large osteochondral defects were surgically generated. The degree of repair was histologically scored after 8 weeks. WNT3a was successfully loaded on exosomes and resulted in activation of WNT signalling in vitro. In vivo, recombinant WNT3a failed to activate WNT signalling in cartilage, whereas a single administration of WNT3a loaded exosomes activated canonical WNT signalling for at least one week, and eight weeks later, improved the repair of osteochondral defects. WNT3a assembled on exosomes, is efficiently delivered into cartilage and contributes to the healing of osteochondral defects.
Abstract
The gravitationally lensed star WHL 0137–LS, nicknamed Earendel, was identified with a photometric redshift
z
phot
= 6.2 ± 0.1 based on images taken with the Hubble Space Telescope. Here we ...present James Webb Space Telescope (JWST) Near Infrared Camera images of Earendel in eight filters spanning 0.8–5.0
μ
m. In these higher-resolution images, Earendel remains a single unresolved point source on the lensing critical curve, increasing the lower limit on the lensing magnification to
μ
> 4000 and restricting the source plane radius further to
r
< 0.02 pc, or ∼4000 au. These new observations strengthen the conclusion that Earendel is best explained by an individual star or multiple star system and support the previous photometric redshift estimate. Fitting grids of stellar spectra to our photometry yields a stellar temperature of
T
eff
≃ 13,000–16,000 K, assuming the light is dominated by a single star. The delensed bolometric luminosity in this case ranges from
log
(
L
)
=
5.8
to 6.6
L
⊙
, which is in the range where one expects luminous blue variable stars. Follow-up observations, including JWST NIRSpec scheduled for late 2022, are needed to further unravel the nature of this object, which presents a unique opportunity to study massive stars in the first billion years of the universe.
Studies measuring the chemical abundances of the neutral gas in star-forming galaxies (SFGs) require ionization correction factors (ICFs) to accurately measure their metal contents. In the work ...presented here, we calculate newly improved ICFs for a sample of SFGs. These new corrections include both the contaminating ionized gas along the line of sight ( ) and unaccounted for higher ionization stages in the neutral gas ( ). We make use of recently acquired spectroscopic observations taken with the Cosmic Origins Spectrograph on board Hubble to measure column densities for Fe ii and Fe iii. Using the Fe iii/Fe ii ratios as well as other physical properties (i.e., log , N(H i), T, and Z), we generate ad hoc photoionization models with CLOUDY to quantify the corrections required for each of the targets. We identify a luminosity threshold of log ∼ 40.75 erg s−1 above which the values for nitrogen are relatively higher ( −0.7) than those for the rest of the elements ( ). This behavior indicates that, for the high UV luminosity objects, N ii is found in non-negligible quantities in the neutral gas, making these corrections critical for determining the true abundances in the interstellar medium. In addition, we calculate ICFs from a uniform grid of models covering a wide range of physical properties typically observed in studies of SFGs and extragalactic H ii regions. We provide the community with tabulated ICF values for the neutral gas abundances measured from a variety of environments and applicable to chemical studies of the high-redshift universe.
Abstract
MACS0647–JD is a triply lensed
z
∼ 11 galaxy originally discovered with the Hubble Space Telescope. The three lensed images are magnified by factors of ∼8, 5, and 2 to AB mag 25.1, 25.6, and ...26.6 at 3.5
μ
m. The brightest is over a magnitude brighter than other galaxies recently discovered at similar redshifts
z
> 10 with JWST. Here, we report new JWST imaging that clearly resolves MACS0647–JD as having two components that are either merging galaxies or stellar complexes within a single galaxy. The brighter larger component “A” is intrinsically very blue (
β
∼ −2.6 ± 0.1), likely due to very recent star formation and no dust, and is spatially extended with an effective radius ∼70 ± 24 pc. The smaller component “B” (
r
∼ 20
−
5
+
8
pc) appears redder (
β
∼ −2 ± 0.2), likely because it is older (100–200 Myr) with mild dust extinction (
A
V
∼ 0.1 mag). With an estimated stellar mass ratio of roughly 2:1 and physical projected separation ∼400 pc, we may be witnessing a galaxy merger 430 million years after the Big Bang. We identify galaxies with similar colors in a high-redshift simulation, finding their star formation histories to be dissimilar, which is also suggested by the spectral energy distribution fitting, suggesting they formed further apart. We also identify a candidate companion galaxy “C” ∼3 kpc away, likely destined to merge with A and B. Upcoming JWST Near Infrared Spectrograph observations planned for 2023 January will deliver spectroscopic redshifts and more physical properties for these tiny magnified distant galaxies observed in the early universe.
We use the Hubble Space Telescope Advanced Camera for Surveys to obtain the first spatially resolved, nebular imaging in the light of C iv λ λ 1548, 1551 by using the F150LP and F165LP filters. These ...observations of the local starburst Mrk 71 in NGC 2366 show emission apparently originating within the interior cavity around the dominant super star cluster (SSC), Knot A. Together with imaging in He ii λ 4686 and supporting Space Telescope Imaging Spectrograph far-ultraviolet spectroscopy, the morphology and intensity of the C iv nebular surface brightness and the C iv/He ii ratio map provide direct evidence that the mechanical feedback is likely dominated by catastrophic radiative cooling, which strongly disrupts adiabatic superbubble evolution. The implied extreme mass loading and low kinetic efficiency of the cluster wind are reasonably consistent with the wind energy budget, which is probably enhanced by radiation pressure. In contrast, the Knot B SSC lies within a well-defined superbubble with associated soft X-rays and He ii λ 1640 emission, which are signatures of adiabatic, energy-driven feedback from a supernova-driven outflow. This system lacks clear evidence of C iv from the limb-brightened shell, as expected for this model, but the observations may not be deep enough to confirm its presence. We also detect a small C iv-emitting object that is likely an embedded compact H ii region. Its C iv emission may indicate the presence of very massive stars (>100 M ⊙ ) or strongly pressure-confined stellar feedback.
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