This paper studies the properties of kiloparsec-scale clumps in star-forming galaxies at z - 2 through multi-wavelength broadband photometry. A sample of 40 clumps is identified from Hubble Space ...Telescope (HST)/Advanced Camera for Surveys (ACS) z-band images through auto-detection and visual inspection from 10 galaxies with 1.5 < z < 2.5 in the Hubble Ultra Deep Field, where deep and high-resolution HST/WFC3 and ACS images enable us to resolve structures of z ~ 2 galaxies down to the kiloparsec scale in the rest-frame UV and optical bands and to detect clumps toward the faint end. Our results are broadly consistent with a widely held view that clumps are formed through gravitational instability in gas-rich turbulent disks and would eventually migrate toward galactic centers and coalesce into bulges. Roughly 40% of the galaxies in our sample contain a massive clump that could be identified as a proto-bulge, which seems qualitatively consistent with such a bulge-formation scenario.
The COVID-19 pandemic has had widespread effects across the globe, and its causative agent, SARS-CoV-2, continues to spread. Effective interventions need to be developed to end this pandemic. Single ...and combination therapies with monoclonal antibodies have received emergency use authorization
, and more treatments are under development
. Furthermore, multiple vaccine constructs have shown promise
, including two that have an approximately 95% protective efficacy against COVID-19
. However, these interventions were directed against the initial SARS-CoV-2 virus that emerged in 2019. The recent detection of SARS-CoV-2 variants B.1.1.7 in the UK
and B.1.351 in South Africa
is of concern because of their purported ease of transmission and extensive mutations in the spike protein. Here we show that B.1.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclonal antibodies against the receptor-binding domain. It is not more resistant to plasma from individuals who have recovered from COVID-19 or sera from individuals who have been vaccinated against SARS-CoV-2. The B.1.351 variant is not only refractory to neutralization by most monoclonal antibodies against the N-terminal domain but also by multiple individual monoclonal antibodies against the receptor-binding motif of the receptor-binding domain, which is mostly due to a mutation causing an E484K substitution. Moreover, compared to wild-type SARS-CoV-2, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4-fold) and sera from individuals who have been vaccinated (10.3-12.4-fold). B.1.351 and emergent variants
with similar mutations in the spike protein present new challenges for monoclonal antibody therapies and threaten the protective efficacy of current vaccines.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Nirmatrelvir, an oral antiviral targeting the 3CL protease of SARS-CoV-2, has been demonstrated to be clinically useful against COVID-19 (refs.
). However, because SARS-CoV-2 has evolved to become ...resistant to other therapeutic modalities
, there is a concern that the same could occur for nirmatrelvir. Here we examined this possibility by in vitro passaging of SARS-CoV-2 in nirmatrelvir using two independent approaches, including one on a large scale. Indeed, highly resistant viruses emerged from both and their sequences showed a multitude of 3CL protease mutations. In the experiment peformed with many replicates, 53 independent viral lineages were selected with mutations observed at 23 different residues of the enzyme. Nevertheless, several common mutational pathways to nirmatrelvir resistance were preferred, with a majority of the viruses descending from T21I, P252L or T304I as precursor mutations. Construction and analysis of 13 recombinant SARS-CoV-2 clones showed that these mutations mediated only low-level resistance, whereas greater resistance required accumulation of additional mutations. E166V mutation conferred the strongest resistance (around 100-fold), but this mutation resulted in a loss of viral replicative fitness that was restored by compensatory changes such as L50F and T21I. Our findings indicate that SARS-CoV-2 resistance to nirmatrelvir does readily arise via multiple pathways in vitro, and the specific mutations observed herein form a strong foundation from which to study the mechanism of resistance in detail and to inform the design of next-generation protease inhibitors.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Galaxy mergers are expected to have a significant role in the mass assembly of galaxies in the early universe, but there are very few observational constraints on the merger history of galaxies at z ...> 2. We present the first study of galaxy major mergers (mass ratios <1:4) in mass-selected samples out to z 6. Using all five fields of the Hubble Space Telescope/CANDELS survey and a probabilistic pair-count methodology that incorporates the full photometric redshift posteriors and corrections for stellar mass completeness, we measure galaxy pair-counts for projected separations between 5 and 30 kpc in stellar mass selected samples at 9.7 < log10(M /M ) < 10.3 and log10(M /M ) > 10.3. We find that the major merger pair fraction rises with redshift to z 6 proportional to (1 + z)m, with m = 0.8 0.2 (m = 1.8 0.2) for log10(M /M ) > 10.3 (9.7 < log10(M /M ) < 10.3). Investigating the pair fraction as a function of mass ratio between 1:20 and 1:1, we find no evidence for a strong evolution in the relative numbers of minor to major mergers out to z < 3. Using evolving merger timescales, we find that the merger rate per galaxy ( ) rises rapidly from 0.07 0.01 Gyr−1 at z < 1 to 7.6 2.7 Gyr−1 at z = 6 for galaxies at log10(M /M ) > 10.3. The corresponding comoving major merger rate density remains roughly constant during this time, with rates of Γ 10−4 Gyr−1 Mpc−3. Based on the observed merger rates per galaxy, we infer specific mass accretion rates from major mergers that are comparable to the specific star formation rates for the same mass galaxies at z > 3 - observational evidence that mergers are as important a mechanism for building up mass at high redshift as in situ star formation.
We study the evolution of the scaling relations that compare the effective density ( ) and core density ( kpc) to the stellar masses of star-forming galaxies (SFGs) and quiescent galaxies. These ...relations have been fully in place since and have exhibited almost constant slope and scatter since that time. For SFGs, the zero points in and decline by only . This fact plus the narrowness of the relations suggests that galaxies could evolve roughly along the scaling relations. Quiescent galaxies follow different scaling relations that are offset to higher densities at the same mass and redshift. Furthermore, the zero point of their core density has declined by only since , while the zero point of the effective density declines by . When galaxies quench, they move from the star-forming relations to the quiescent relations. This involves an increase in the core and effective densities, which suggests that SFGs could experience a phase of significant core growth relative to the average evolution along the structural relations. The distribution of massive galaxies relative to the SFR-M and the quiescent relations exhibits an L-shape that is independent of redshift. The knee of this relation consists of a subset of "compact" SFGs that are the most likely precursors of quiescent galaxies forming at later times. The compactness selection threshold in exhibits a small variation from z = 3 to 0.5, M kpc−2, allowing the most efficient identification of compact SFGs and quiescent galaxies at every redshift.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2.75 emerged recently and appears to be spreading. It has nine mutations in spike compared with the currently ...circulating BA.2, raising concerns that it may further evade vaccine-elicited and therapeutic antibodies. We found BA.2.75 to be moderately more neutralization resistant to sera from vaccinated/boosted individuals than BA.2 (1.8-fold), similar to BA.2.12.1 (1.1-fold), but more neutralization sensitive than BA.4/5 (0.6-fold). Relative to BA.2, BA.2.75 showed heightened resistance to class 1 and class 3 monoclonal antibodies targeting the spike-receptor-binding domain while gaining sensitivity to class 2 antibodies. Resistance was largely conferred by G446S and R460K mutations. BA.2.75 was slightly resistant (3.7-fold) to bebtelovimab, a therapeutic antibody with potent activity against all Omicron subvariants. BA.2.75 also exhibited a higher binding affinity to host receptor ACE2 than other Omicron subvariants. BA.2.75 provides further insight into SARS-CoV-2 evolution as it gains transmissibility while incrementally evading antibody neutralization.
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•BA.2.75 is more resistant to neutralization by polyclonal sera than BA.2•BA.2.75 shows heightened resistance to class 1 and class 3 RBD-directed antibodies•BA.2.75 is the first variant to show discernible resistance to bebtelovimab•BA.2.75 exhibits higher human ACE2-binding affinity than other Omicron subvariants
Wang et al. have systematically evaluated the antigenic properties of the new SARS-CoV-2 Omicron subvariant BA.2.75. They found that BA.2.75 exhibits greater neutralization resistance to monoclonal antibodies and vaccine- and infection-induced sera than previous Omicron subvariant BA.2, while showing a higher binding affinity for human ACE2.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Studying giant star-forming clumps in distant galaxies is important to understand galaxy formation and evolution. At present, however, observers and theorists have not reached a consensus on whether ...the observed "clumps" in distant galaxies are the same phenomenon that is seen in simulations. In this paper, as a step to establish a benchmark of direct comparisons between observations and theories, we publish a sample of clumps constructed to represent the commonly observed "clumps" in the literature. This sample contains 3193 clumps detected from 1270 galaxies at 0.5 ≤ z < 3.0 . The clumps are detected from rest-frame UV images, as described in our previous paper. Their physical properties (e.g., rest-frame color, stellar mass ( M * ), star formation rate (SFR), age, and dust extinction) are measured by fitting the spectral energy distribution (SED) to synthetic stellar population models. We carefully test the procedures of measuring clump properties, especially the method of subtracting background fluxes from the diffuse component of galaxies. With our fiducial background subtraction, we find a radial clump U − V color variation, where clumps close to galactic centers are redder than those in outskirts. The slope of the color gradient (clump color as a function of their galactocentric distance scaled by the semimajor axis of galaxies) changes with redshift and M * of the host galaxies: at a fixed M * , the slope becomes steeper toward low redshift, and at a fixed redshift, it becomes slightly steeper with M * . Based on our SED fitting, this observed color gradient can be explained by a combination of a negative age gradient, a negative E(B − V) gradient, and a positive specific SFR gradient of the clumps. We also find that the color gradients of clumps are steeper than those of intra-clump regions. Correspondingly, the radial gradients of the derived physical properties of clumps are different from those of the diffuse component or intra-clump regions.
A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant, BA.2.86, has emerged and spread to numerous countries worldwide, raising alarm because its spike protein contains 34 ...additional mutations compared with its BA.2 predecessor
. We examined its antigenicity using human sera and monoclonal antibodies (mAbs). Reassuringly, BA.2.86 was no more resistant to human sera than the currently dominant XBB.1.5 and EG.5.1, indicating that the new subvariant would not have a growth advantage in this regard. Importantly, sera from people who had XBB breakthrough infection exhibited robust neutralizing activity against all viruses tested, suggesting that upcoming XBB.1.5 monovalent vaccines could confer added protection. Although BA.2.86 showed greater resistance to mAbs to subdomain 1 (SD1) and receptor-binding domain (RBD) class 2 and 3 epitopes, it was more sensitive to mAbs to class 1 and 4/1 epitopes in the 'inner face' of the RBD that is exposed only when this domain is in the 'up' position. We also identified six new spike mutations that mediate antibody resistance, including E554K that threatens SD1 mAbs in clinical development. The BA.2.86 spike also had a remarkably high receptor affinity. The ultimate trajectory of this new SARS-CoV-2 variant will soon be revealed by continuing surveillance, but its worldwide spread is worrisome.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
The recently reported B.1.1.529 Omicron variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) includes 34 mutations in the spike protein relative to the Wuhan strain, including 15 ...mutations in the receptor-binding domain (RBD). Functional studies have shown Omicron to substantially escape the activity of many SARS-CoV-2-neutralizing antibodies. Here, we report a 3.1 Å-resolution cryoelectron microscopy (cryo-EM) structure of the Omicron spike protein ectodomain. The structure depicts a spike that is exclusively in the 1-RBD-up conformation with high mobility of RBD. Many mutations cause steric clashes and/or altered interactions at antibody-binding surfaces, whereas others mediate changes of the spike structure in local regions to interfere with antibody recognition. Overall, the structure of the Omicron spike reveals how mutations alter its conformation and explains its extraordinary ability to evade neutralizing antibodies.
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•SARS-CoV-2 Omicron spike exclusively adopts a 1-RBD-up conformation•Omicron substitutions alter conformation and mobility of the RBD•A subset of Omicron mutations changes the local conformation of spike•The structure reveals the basis of antibody neutralization escape
Cerutti et al. report the cryo-EM structure of the SARS-CoV-2 Omicron spike in its ligand-free form. The structure elucidates the effect of the mutations on the global and local conformation of spike and explains the antibody resistance to the Omicron variant.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
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