A Wide Range of 3243A>G/tRNALeu(UUR) (MELAS) Mutation Loads May Segregate in Offspring through the Female Germline Bottleneck

Segregation of mutant mtDNA in human tissues and through the germline is debated, with no consensus about the nature and size of the bottleneck hypothesized to explain rapid generational shifts in mutant loads. We investigated two maternal lineages with an apparently different inheritance pattern of the same pathogenic mtDNA 3243A>G/tRNALeu(UUR) (MELAS) mutation. We collected blood cells, muscle biopsies, urinary epithelium and hair follicles from 20 individuals, as well as oocytes and an ovarian biopsy from one female mutation carrier, all belonging to the two maternal lineages to assess mutant mtDNA load, and calculated the theoretical germline bottleneck size (number of segregating units). We also evaluated “mother-to-offspring” segregations from the literature, for which heteroplasmy assessment was available in at least three siblings besides the proband. Our results showed that mutation load was prevalent in skeletal muscle and urinary epithelium, whereas in blood cells there was an inverse correlation with age, as previously reported. The histoenzymatic staining of the ovarian biopsy failed to show any cytochrome-c-oxidase defective oocyte. Analysis of four oocytes and one offspring from the same unaffected mother of the first family showed intermediate heteroplasmic mutant loads (10% to 75%), whereas very skewed loads of mutant mtDNA (0% or 81%) were detected in five offspring of another unaffected mother from the second family. Bottleneck size was 89 segregating units for the first mother and 84 for the second. This was remarkably close to 88, the number of “segregating units” in the “mother-to-offspring” segregations retrieved from literature. In conclusion, a wide range of mutant loads may be found in offspring tissues and oocytes, resulting from a similar theoretical bottleneck size

A massive quiescent galaxy in a group environment at z=4.53z=4.53

We report on the spectroscopic confirmation of a massive quiescent galaxy at $z_\mathrm{spec}=4.53$ in the COSMOS field with Keck/MOSFIRE. The object was first identified as a galaxy with suppressed star formation at $z_\mathrm{phot}\sim4.65$ from the COSMOS2020 catalog. The follow-up spectroscopy with MOSFIRE in the $K$-band reveals a faint [OII] emission and the Balmer break, indicative of evolved stellar populations. We perform the spectral energy distribution fitting using both the photometry and spectrum to infer physical properties. The obtained stellar mass is high ($M_*\sim 10^{10.8}\,M_\odot$) and the current star formation rate is more than 1 dex below that of main-sequence galaxies at $z=4.5$. Its star formation history suggests that this galaxy experienced starburst at $z\sim5$ followed by a rapid quenching phase. This is one of the youngest quiescent galaxies at $z>3$ and is likely a galaxy in the process of being quenched. An unique aspect of the galaxy is that it is in an extremely dense region; there are four massive star-forming galaxies at $4.4<z_\mathrm{phot}<4.7$ located within 150 physical kpc from the galaxy. Interestingly, three of them have strongly overlapping virial radii with that of the central quiescent galaxy ($\sim 70\,\mathrm{kpc}$), suggesting that the over-density region is likely the highest redshift candidate of a dense group with a spectroscopically confirmed quiescent galaxy at the center. The group provides us with an unique opportunity to gain insights into the role of the group environment for quenching at $z\sim$ 4 - 5 corresponding to the formation epoch of massive elliptical galaxies in the local Universe.Comment: 13 pages, 7 figures, 2 tables; submitted to Ap

The archival discovery of a strong Lyman-α\alpha and [CII] emitter at z = 7.677

We report the archival discovery of Lyman-$\alpha$ emission from the bright ultraviolet galaxy Y002 at $z=7.677$, spectroscopically confirmed by its ionized carbon [CII] 158$\mu$m emission line. The Ly$\alpha$ line is spatially associated with the rest-frame UV stellar emission ($M_{\rm UV}$~-22, 2x brighter than $M^\star_{\rm UV}$) and it appears offset from the peak of the extended [CII] emission at the current ~1" spatial resolution. We derive an estimate of the unobscured SFR(UV)=$(22\pm1)\,M_\odot$ yr$^{-1}$ and set an upper limit of SFR(IR)$<15\,M_\odot$ yr$^{-1}$ from the far-infrared wavelength range, which globally place Y002 on the SFR(UV+IR)-L([CII]) correlation observed at lower redshifts. In terms of velocity, the peak of the Ly$\alpha$ emission is redshifted by $\Delta v$(Ly$\alpha$)~500 km s$^{-1}$ from the systemic redshift set by [CII] and a high-velocity tail extends to up to ~1000 km s$^{-1}$. The velocity offset is up to ~3.5x higher than the average estimate for similarly UV-bright emitters at z~6-7, which might suggest that we are witnessing the merging of two clumps. A combination of strong outflows and the possible presence of an extended ionized bubble surrounding Y002 would likely facilitate the escape of copious Ly$\alpha$ light, as indicated by the large equivalent width EW(Ly$\alpha$)=$24^{+5}_{-6}$ \r{A}. Assuming that [CII] traces the neutral hydrogen, we estimate a HI gas fraction of $M({\rm HI})/M_\star\gtrsim8$ for Y002 as a system and speculate that patches of high HI column densities could contribute to explain the observed spatial offsets between Ly$\alpha$ and [CII] emitting regions. The low dust content, implied by the non-detection of the far-infrared continuum emission at rest-frame ~160 $\mu$m, would be sufficient to absorb any potential Ly$\alpha$ photons produced within the [CII] clump as a result of large HI column densities.Comment: 10 pages, 4 figures. Accepted for publication in The Astrophysical Journal Letter

COSMOS2020: Discovery of a protocluster of massive quiescent galaxies at z=2.77z=2.77

Protoclusters of galaxies have been found in the last quarter century. However, most of them have been found through the overdensity of star-forming galaxies, and there had been no known structures identified by multiple spectroscopically confirmed quiescent galaxies at $z>2.5$. In this letter, we report the discovery of an overdense structure of massive quiescent galaxies with the spectroscopic redshift $z=2.77$ in the COSMOS field, QO-1000. We first photometrically identify this structure as a $4.2\sigma$ overdensity with 14 quiescent galaxies in $7\times4\ {\rm pMpc^2}$ from the COSMOS2020 catalog. We then securely confirm the spectroscopic redshifts of 4 quiescent galaxies by detecting multiple Balmer absorption lines with Keck/MOSFIRE. All the spectroscopically confirmed members are massive ($\log{(M_\star/M_\odot)}>11.0$) and located in a narrow redshift range ($2.76<z<2.79$). Moreover, three of them are in the $1\times1\ {\rm pMpc^2}$ in the transverse direction at the same redshift ($z=2.760-2.763$). Such a concentration of four spectroscopically confirmed quiescent galaxies implies that QO-1000 is $>68$ times denser than in the general field. In addition, we confirm that they form a red sequence in the $J-K_s$ color. This structure's halo mass is estimated as $\log{(M_{\rm halo}/M_\odot)}>13.2$ from their stellar mass. Similar structures found in the IllustrisTNG simulation are expected to evolve into massive galaxy clusters with $\log{(M_{\rm halo}/M_\odot)}\geq14.8$ at $z=0$. These results suggest that QO-1000 is a more mature protocluster than the other known protoclusters. It is likely in a transition phase between the star-forming protoclusters and the quenched galaxy clusters.Comment: 11 pages, 4 figures, 1 table, accepted for publication in ApJ

Stellar Velocity Dispersion of a Massive Quenching Galaxy at z = 4.01

We present the first stellar velocity dispersion measurement of a massive quenching galaxy at z = 4. The galaxy is first identified as a massive z ≥ 4 galaxy with suppressed star formation from photometric redshifts based on deep multiband data. A follow-up spectroscopic observation with MOSFIRE on Keck revealed strong multiple absorption features, which are identified as Balmer lines, giving a secure redshift of z = 4.01. This is the most distant quiescent galaxy known to date. Thanks to the high S/N of the spectrum, we are able to estimate the stellar velocity dispersion, σ=268±59 km s⁻¹, making a significant leap from the previous highest redshift measurement at z = 2.8. Interestingly, we find that the velocity dispersion is consistent with that of massive galaxies today, implying no significant evolution in velocity dispersion over the last 12 Gyr. Based on a stringent upper limit on its physical size from deep optical images (r_(eff) < 1.3 kpc), we find that its dynamical mass is consistent with the stellar mass inferred from photometry. Furthermore, the galaxy is located on the mass fundamental plane extrapolated from lower redshift galaxies. The observed no strong evolution in σ suggests that the mass in the core of massive galaxies does not evolve significantly, while most of the mass growth occurs in the outskirts of the galaxies, which also increases the size. This picture is consistent with a two-phase formation scenario in which mass and size growth is due to accretion in the outskirts of galaxies via mergers. Our results imply that the first phase may be completed as early as z ~ 4

Grand Rounds: Could Occupational Exposure to n-Hexane and Other Solvents Precipitate Visual Failure in Leber Hereditary Optic Neuropathy?

CONTEXT: Leber hereditary optic neuropathy (LHON) is a maternally inherited loss of central vision related to pathogenic mutations in the mitochondrial genome, which are a necessary but not sufficient condition to develop the disease. Investigation of precipitating environmental/occupational (and additional genetic) factors could be relevant for prevention. CASE PRESENTATION: After a 6-month period of occupational exposure to n-hexane and other organic solvents, a 27-year-old man (a moderate smoker) developed an optic neuropathy. The patient had a full ophthalmologic and neurologic investigation, including standardized cycloergometer test for serum lactic acid levels and a skeletal muscle biopsy. His exposure history was also detailed, and he underwent genetic testing for LHON mitochondrial DNA mutations. The patient suffered a sequential optic neuropathy with the hallmarks of LHON and tested positive for the homoplasmic 11778G → A/ND4 mutation. Routine laboratory monitoring revealed increased concentrations of urinary 2.5 hexandione (n-hexane metabolite) and hippuric acid (toluene metabolite) in the period immediately preceding the visual loss. DISCUSSION: In a subject carrying an LHON mutation, the strict temporal sequence of prolonged appreciable occupational exposure followed by sudden onset of visual loss must raise a suspicion of causality (with a possible further interaction with tobacco smoke). RELEVANCE: In this article, we add to the candidate occupational/environmental triggers of LHON and highlight the need for appropriate case–control (and laboratory) studies to validate the causal effect of mixed toxic exposures

COSMOS2020: Exploring the dawn of quenching for massive galaxies at 3 < z < 5 with a new colour selection method

We select and characterise a sample of massive (log(M$_{*}/$M$_{\odot})>10.6$) quiescent galaxies (QGs) at $3<z<5$ in the latest COSMOS2020 catalogue. QGs are selected using a new rest-frame colour selection method, based on their probability of belonging to the quiescent group defined by a Gaussian Mixture Model (GMM) trained on rest-frame colours ($NUV-U, U-V, V-J$) of similarly massive galaxies at $2<z<3$. We calculate the quiescent probability threshold above which a galaxy is classified as quiescent using simulated galaxies from the SHARK semi-analytical model. We find that at $z\geq3$ in SHARK, the GMM/$NUVU-VJ$ method out-performs classical rest-frame $UVJ$ selection and is a viable alternative. We select galaxies as quiescent based on their probability in COSMOS2020 at $3<z<5$, and compare the selected sample to both $UVJ$ and $NUVrJ$ selected samples. We find that although the new selection matches $UVJ$ and $NUVrJ$ in number, the overlap between colour selections is only $\sim50-80\%$, implying that rest-frame colour commonly used at lower redshifts selections cannot be equivalently used at $z>3$. We compute median rest-frame SEDs for our sample and find the median quiescent galaxy at $3<z<5$ has a strong Balmer/4000 Angstrom break, and residual $NUV$ flux indicating recent quenching. We find the number densities of the entire quiescent population (including post-starbursts) more than doubles from $3.5\pm2.2\times10^{-6}$ Mpc$^{-3}$ at $4<z<5$ to $1.4\pm0.4\times10^{-5}$ Mpc$^{-3}$ at $3<z<4$, confirming that the onset of massive galaxy quenching occurs as early as $3<z<5$.Comment: 19 pages, 10 figures + appendix. Accepted for publication in AJ. Both the GMM model and code to calculate quiescent probabilities from rest frame flux densities are made available online at https://github.com/kmlgould/GMM-quiescen

Hsp60 response in experimental and human temporal lobe epilepsy

The mitochondrial chaperonin Hsp60 is a ubiquitous molecule with multiple roles, constitutively expressed and inducible by oxidative stress. In the brain, Hsp60 is widely distributed and has been implicated in neurological disorders, including epilepsy. A role for mitochondria and oxidative stress has been proposed in epileptogenesis of temporal lobe epilepsy (TLE). Here, we investigated the involvement of Hsp60 in TLE using animal and human samples. Hsp60 immunoreactivity in the hippocampus, measured by Western blotting and immunohistochemistry, was increased in a rat model of TLE. Hsp60 was also increased in the hippocampal dentate gyrus neurons somata and neuropil and hippocampus proper (CA3, CA1) of the epileptic rats. We also determined the circulating levels of Hsp60 in epileptic animals and TLE patients using ELISA. The epileptic rats showed circulating levels of Hsp60 higher than controls. Likewise, plasma post-seizure Hsp60 levels in patients were higher than before the seizure and those of controls. These results demonstrate that Hsp60 is increased in both animals and patients with TLE in affected tissues, and in plasma in response to epileptic seizures, and point to it as biomarker of hippocampal stress potentially useful for diagnosis and patient management.peer-reviewe

Hsp60 response in experimental and human temporal lobe epilepsy

The mitochondrial chaperonin Hsp60 is a ubiquitous molecule with multiple roles, constitutively expressed and inducible by oxidative stress. In the brain, Hsp60 is widely distributed and has been implicated in neurological disorders, including epilepsy. A role for mitochondria and oxidative stress has been proposed in epileptogenesis of temporal lobe epilepsy (TLE). Here, we investigated the involvement of Hsp60 in TLE using animal and human samples. Hsp60 immunoreactivity in the hippocampus, measured by Western blotting and immunohistochemistry, was increased in a rat model of TLE. Hsp60 was also increased in the hippocampal dentate gyrus neurons somata and neuropil and hippocampus proper (CA3, CA1) of the epileptic rats. We also determined the circulating levels of Hsp60 in epileptic animals and TLE patients using ELISA. The epileptic rats showed circulating levels of Hsp60 higher than controls. Likewise, plasma post-seizure Hsp60 levels in patients were higher than before the seizure and those of controls. These results demonstrate that Hsp60 is increased in both animals and patients with TLE in affected tissues, and in plasma in response to epileptic seizures, and point to it as biomarker of hippocampal stress potentially useful for diagnosis and patient management.peer-reviewe