We present two bright galaxy candidates at z ∼ 12–13 identified in our H-dropout Lyman break selection with 2.3 deg(exp 2) near-infrared deep imaging data. These galaxy candidates, selected after ...careful screening of foreground interlopers, have spectral energy distributions showing a sharp discontinuity around 1.7 μm, a flat continuum at 2–5 μm, and nondetections at <1.2 μm in the available photometric data sets, all of which are consistent with a z > 12 galaxy. An ALMA program targeting one of the candidates shows a tentative 4σ O III 88 μm line at z = 13.27, in agreement with its photometric redshift estimate. The number density of the z ∼ 12–13 candidates is comparable to that of bright z ∼ 10 galaxies and is consistent with a recently proposed double-power-law luminosity function rather than the Schechter function, indicating little evolution in the abundance of bright galaxies from z ∼ 4 to 13. Comparisons with theoretical models show that the models cannot reproduce the bright end of rest-frame ultraviolet luminosity functions at z ∼ 10–13. Combined with recent studies reporting similarly bright galaxies at z ∼ 9–11 and mature stellar populations at z ∼ 6–9, our results indicate the existence of a number of star-forming galaxies at z > 10, which will be detected with upcoming space missions such as the James Webb Space Telescope, Nancy Grace Roman Space Telescope, and GREX-PLUS.
A fundamental quest of modern astronomy is to locate the earliest galaxies and study how they influenced the intergalactic medium a few hundred million years after the Big Bang
. The abundance of ...star-forming galaxies is known to decline
from redshifts of about 6 to 10, but a key question is the extent of star formation at even earlier times, corresponding to the period when the first galaxies might have emerged. Here we report spectroscopic observations of MACS1149-JD1
, a gravitationally lensed galaxy observed when the Universe was less than four per cent of its present age. We detect an emission line of doubly ionized oxygen at a redshift of 9.1096 ± 0.0006, with an uncertainty of one standard deviation. This precisely determined redshift indicates that the red rest-frame optical colour arises from a dominant stellar component that formed about 250 million years after the Big Bang, corresponding to a redshift of about 15. Our results indicate that it may be possible to detect such early episodes of star formation in similar galaxies with future telescopes.
The physical properties and elemental abundances of the interstellar medium in galaxies during cosmic reionization are important for understanding the role of galaxies in this process. We report the ...Atacama Large Millimeter/submillimeter Array detection of an oxygen emission line at a wavelength of 88 micrometers from a galaxy at an epoch about 700 million years after the Big Bang. The oxygen abundance of this galaxy is estimated at about one-tenth that of the Sun. The nondetection of far-infrared continuum emission indicates a deficiency of interstellar dust in the galaxy. A carbon emission line at a wavelength of 158 micrometers is also not detected, implying an unusually small amount of neutral gas. These properties might allow ionizing photons to escape into the intergalactic medium.
ABSTRACT Recent observations with the Atacama Large Millimeter/submillimeter Array (ALMA) detected far-infrared emission lines such as the O iii $88\,\mu \mathrm{ m}$ line from galaxies at z ∼ 7−9. ...We use a cosmological simulation of galaxy formation to study the physical properties of O iii $88\,\mu \mathrm{ m}$ emitters. In a comoving volume of 50 h−1 Mpc on a side, we locate 34 galaxies with stellar masses greater than $10^8\ \rm M_{\odot }$ at z = 9, and more than 270 such galaxies at z = 7. We calculate the O iii $88\,\mu \mathrm{ m}$ luminosities ($L_{{\rm O\,{{\rm {\small{III}}}, 88}}}$) by combining a physical model of H ii regions with emission line calculations using the photoionization code cloudy. We show that the resulting $L_{{\rm O\,{{\rm {\small{III}}}, 88}}}$, for a given star formation rate, is slightly higher than predicted from the empirical relation for local galaxies, and is consistent with recent observations of galaxies at redshifts 7–9. Bright O iii emitters with $L_{{\rm O\,{{\rm {\small{III}}}, 88}}}\gt 10^8\, \rm L_{\odot }$ have star formation rates higher than $3\,\rm M_{\odot }\,{\rm yr}^{-1}$, and the typical metallicity is ${\sim } 0.1\, \rm Z_{\odot }$. The galaxies are hosted by dark matter haloes with masses greater than $10^{11}\, \rm M_{\odot }$. We propose to use the O iii 5007 Å line, to be detected by James Webb Space Telescope, to study the properties of galaxies whose O iii $88\,\mu \mathrm{ m}$ line emission has been already detected with ALMA.
Abstract
We present spatially resolved morphological properties of C
II
158
μ
m, O
III
88
μ
m, dust, and rest-frame ultraviolet (UV) continuum emission for A1689-zD1, a strongly lensed, sub-L* ...galaxy at
z
= 7.13, by utilizing deep Atacama Large Millimeter/submillimeter Array (ALMA) and Hubble Space Telescope (HST) observations. While the O
III
line and UV continuum are compact, the C
II
line is extended up to a radius of
r
∼ 12 kpc. Using multi-band rest-frame far-infrared continuum data ranging from 52 to 400
μ
m, we find an average dust temperature and emissivity index of
T
dust
=
41
−
14
+
17
K and
β
=
1.7
−
0.7
+
1.1
, respectively, across the galaxy. We find slight differences in the dust continuum profiles at different wavelengths, which may indicate that the dust temperature decreases with distance. We map the star formation rate (SFR) via IR and UV luminosities and determine a total SFR of 37 ± 1
M
⊙
yr
−1
with an obscured fraction of 87%. While the O
III
line is a good tracer of the SFR, the C
II
line shows deviation from the local
L
C
II
-SFR relations in the outskirts of the galaxy. Finally, we observe a clear difference in the line profile between C
II
and O
III
, with significant residuals (∼5
σ
) in the O
III
line spectrum after subtracting a single Gaussian model. This suggests a possible origin of the extended C
II
structure from the cooling of hot ionized outflows. The extended C
II
and high-velocity O
III
emission may both contribute in part to the high
L
O
III
/
L
C
II
ratios recently reported in
z
> 6 galaxies.
Nucleic acid editing enzymes are essential components of the immune system that lethally mutate viral pathogens and somatically mutate immunoglobulins, and contribute to the diversification and ...lethality of cancers. Among these enzymes are the seven human APOBEC3 deoxycytidine deaminases, each with unique target sequence specificity and subcellular localization. While the enzymology and biological consequences have been extensively studied, the mechanism by which APOBEC3s recognize and edit DNA remains elusive. Here we present the crystal structure of a complex of a cytidine deaminase with ssDNA bound in the active site at 2.2 Å. This structure not only visualizes the active site poised for catalysis of APOBEC3A, but pinpoints the residues that confer specificity towards CC/TC motifs. The APOBEC3A-ssDNA complex defines the 5'-3' directionality and subtle conformational changes that clench the ssDNA within the binding groove, revealing the architecture and mechanism of ssDNA recognition that is likely conserved among all polynucleotide deaminases, thereby opening the door for the design of mechanistic-based therapeutics.
Great effort has been devoted to discovering the basis of A3G-Vif interaction, the key event of HIV's counteraction mechanism to evade antiviral innate immune response. Here we show reconstitution of ...the A3G-Vif complex and subsequent A3G ubiquitination in vitro and report the cryo-EM structure of the A3G-Vif complex at 2.8 Å resolution using solubility-enhanced variants of A3G and Vif. We present an atomic model of the A3G-Vif interface, which assembles via known amino acid determinants. This assembly is not achieved by protein-protein interaction alone, but also involves RNA. The cryo-EM structure and in vitro ubiquitination assays identify an adenine/guanine base preference for the interaction and a unique Vif-ribose contact. This establishes the biological significance of an RNA ligand. Further assessment of interactions between A3G, Vif, and RNA ligands show that the A3G-Vif assembly and subsequent ubiquitination can be controlled by amino acid mutations at the interface or by polynucleotide modification, suggesting that a specific chemical moiety would be a promising pharmacophore to inhibit the A3G-Vif interaction.
The human APOBEC3G protein is a cytidine deaminase that generates cytidine to deoxy-uridine mutations in single-stranded DNA (ssDNA), and capable of restricting replication of HIV-1 by generating ...mutations in viral genome. The mechanism by which APOBEC3G specifically deaminates 5'-CC motifs has remained elusive since structural studies have been hampered due to apparently weak ssDNA binding of the catalytic domain of APOBEC3G. We overcame the problem by generating a highly active variant with higher ssDNA affinity. Here, we present the crystal structure of this variant complexed with a ssDNA substrate at 1.86 Å resolution. This structure reveals atomic-level interactions by which APOBEC3G recognizes a functionally-relevant 5'-TCCCA sequence. This complex also reveals a key role of W211 in substrate recognition, implicating a similar recognition in activation-induced cytidine deaminase (AID) with a conserved tryptophan.
Background:Guidelines for peripheral arterial disease (PAD) recommend long-term antiplatelet therapy in symptomatic patients to reduce cardiovascular morbidity and mortality risk. Although diabetes ...is a known risk factor for PAD, PAD has been undertreated in these patients. This study aimed to evaluate risk factors for major amputation in patients with diabetes undergoing antiplatelet therapy for PAD.Methods and Results:This retrospective analysis of a 2-year observational cohort study (1,745 clinics in Japan, September 2009–2013) evaluated predictors of amputation in patients with diabetes undergoing antiplatelet therapy for PAD. Among 4,016 eligible patients, 52 had an amputation during follow-up. Amputation risk (Cox regression analysis) was predicted at baseline by history of lower extremity revascularization/amputation (hazard ratio HR: 2.92; 95% confidence interval CI: 1.39, 6.14), chronic kidney disease (HR: 4.19; 95% CI: 1.95, 8.97), and comorbid cerebrovascular and heart disease (HR: 3.32; 95% CI: 1.19, 9.30), and was unaffected by choice of oral antiplatelet therapy. In patients with PAD and diabetes, amputation event rate was highest for those with ankle-brachial pressure index (ABI) <0.40 and progressively decreased at higher ABI cut-offs.Conclusions:These findings inform real-world understanding of PAD in diabetic patients receiving antiplatelet therapy in Japan, and showed that ABI <0.4 was the strongest risk factor for amputation.
The human cytidine deaminase family of APOBEC3s (A3s) plays critical roles in both innate immunity and the development of cancers. A3s comprise seven functionally overlapping but distinct members ...that can be exploited as nucleotide base editors for treating genetic diseases. Although overall structurally similar, A3s have vastly varying deamination activity and substrate preferences. Recent crystal structures of ssDNA-bound A3s together with experimental studies have provided some insights into distinct substrate specificities among the family members. However, the molecular interactions responsible for their distinct biological functions and how structure regulates substrate specificity are not clear. In this study, we identified the structural basis of substrate specificities in three catalytically active A3 domains whose crystal structures have been previously characterized: A3A, A3B- CTD, and A3G-CTD. Through molecular modeling and dynamic simulations, we found an interdependency between ssDNA substrate binding conformation and nucleotide sequence specificity. In addition to the U-shaped conformation seen in the crystal structure with the CTC0 motif, A3A can accommodate the CCC0 motif when ssDNA is in a more linear (L) conformation. A3B can also bind both U- and L-shaped ssDNA, unlike A3G, which can stably recognize only linear ssDNA. These varied conformations are stabilized by sequence-specific interactions with active site loops 1 and 7, which are highly variable among A3s. Our results explain the molecular basis of previously observed substrate specificities in A3s and have implications for designing A3-specific inhibitors for cancer therapy as well as engineering base-editing systems for gene therapy.
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