Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung

IntroductionGlobal microplastic (MP) pollution is now well recognized, with humans and animals consuming and inhaling MPs on a daily basis, with a growing body of concern surrounding the potential impacts on human health.MethodsUsing a mouse model of mild COVID-19, we describe herein the effects of azide-free 1 μm polystyrene MP beads, co-delivered into lungs with a SARS-CoV-2 omicron BA.5 inoculum. The effect of MPs on the host response to SARS-CoV-2 infection was analysed using histopathology and RNA-Seq at 2 and 6 days post-infection (dpi).ResultsAlthough infection reduced clearance of MPs from the lung, virus titres and viral RNA levels were not significantly affected by MPs, and overt MP-associated clinical or histopathological changes were not observed. However, RNA-Seq of infected lungs revealed that MP exposure suppressed innate immune responses at 2 dpi and increased pro-inflammatory signatures at 6 dpi. The cytokine profile at 6 dpi showed a significant correlation with the ‘cytokine release syndrome’ signature observed in some COVID-19 patients.DiscussionThe findings are consistent with the recent finding that MPs can inhibit phagocytosis of apoptotic cells via binding of Tim4. They also add to a growing body of literature suggesting that MPs can dysregulate inflammatory processes in specific disease settings

The JWST Extragalactic Mock Catalog: Modeling Galaxy Populations from the UV through the Near-IR over 13 Billion Years of Cosmic History

We present an original phenomenological model to describe the evolution of galaxy number counts, morphologies, and spectral energy distributions across a wide range of redshifts (0.26]. Our model follows observed mass and luminosity functions of both star-forming and quiescent galaxies, and reproduces the redshift evolution of colors, sizes, star-formation and chemical properties of the observed galaxy population. Unlike other existing approaches, our model includes a self-consistent treatment of stellar and photoionized gas emission and dust attenuation based on the BEAGLE tool. The mock galaxy catalogs generated with our new model can be used to simulate and optimize extragalactic surveys with future facilities such as the James Webb Space Telescope (JWST), and to enable critical assessments of analysis procedures, interpretation tools, and measurement systematics for both photometric and spectroscopic data. As a first application of this work, we make predictions for the upcoming JWST Advanced Deep Extragalactic Survey (JADES), a joint program of the JWST/NIRCam and NIRSpec Guaranteed Time Observations teams. We show that JADES will detect, with NIRCam imaging, thousands of galaxies at z>6, and tens at z>10 at m_AB8, and resolve the current debate about the rate of evolution of galaxies at z>8. Ready to use mock catalogs and software to generate new realizations are publicly available as the JAdes extraGalactic Ultradeep Artificial Realizations (JAGUAR) package.ECL, JC and SCh acknowledge support from the European Research Council (ERC) via an Advanced Grant under grant agreement no. 321323- NEOGAL. CCW acknowledges support from the National Science Foundation Astronomy and Astrophysics Fellowship grant AST-1701546. SCh acknowledges financial support from the Science and Technology Facilities Council (STFC). All members of NIRCam (CCW, KNH, BER, RE, DPS, CNAW, SAl, SB, SCr, EE, DJE, MR) acknowledge funding from JWST/NIRCam contract to the University of Arizona, NAS5-02015. BER acknowledges partial support through NASA contract NNG16PJ25C, grants 17-ATP17- 0034 and HST-GO-14747. SAr is funded by MINECO under grant ESP2015-68964-P. RM and RA acknowledge ERC Advanced Grant 695671 "QUENCH” and support by the Science and Technology Facilities Council (STFC). RS acknowledges a NWO Rubicon grant, project number 680-50- 1518. This work is based on observations taken by the CANDELS Multi-cycle Treasury Program with the NASA/ESA HST

SHARDS frontier fields: physical properties of a low-mass Lyα emitter at z = 5.75

We analyze the properties of a multiply-imaged Lyman-alpha (Lya) emitter at z=5.75 identified through SHARDS Frontier Fields intermediate-band imaging of the Hubble Frontier Fields (HFF) cluster Abell 370. The source, A370-L57, has low intrinsic luminosity (M_UV~-16.5), steep UV spectral index (\beta=-2.4+/-0.1), and extreme rest-frame equivalent width of Lya (EW(Lya)=420+180-120 \AA). Two different gravitational lens models predict high magnification (\mu~10--16) for the two detected counter-images, separated by 7", while a predicted third counter-image (\mu~3--4) is undetected. We find differences of ~50% in magnification between the two lens models, quantifying our current systematic uncertainties. Integral field spectroscopy of A370-L57 with MUSE shows a narrow (FWHM=204+/-10 km/s) and asymmetric Lya profile with an integrated luminosity L(Lya)~10^42 erg/s. The morphology in the HST bands comprises a compact clump (r_e<100 pc) that dominates the Lya and continuum emission and several fainter clumps at projected distances <1 kpc that coincide with an extension of the Lya emission in the SHARDS F823W17 and MUSE observations. The latter could be part of the same galaxy or an interacting companion. We find no evidence of contribution from AGN to the Lya emission. Fitting of the spectral energy distribution with stellar population models favors a very young (t<10 Myr), low mass (M*~10^6.5 Msun), and metal poor (Z<4x10^-3) stellar population. Its modest star formation rate (SFR~1.0 Msun/yr) implies high specific SFR (sSFR~2.5x10^-7 yr^-1) and SFR density (Sigma_SFR ~ 7-35 Msun/yr/kpc^2). The properties of A370-L57 make it a good representative of the population of galaxies responsible for cosmic reionization.Comment: 14 pages, 8 figures, 4 tables. Accepted for publication in Ap

A small and vigorous black hole in the early Universe

Several theories have been proposed to describe the formation of black hole seeds in the early Universe and to explain the emergence of very massive black holes observed in the first thousand million years after the Big Bang1–3. Models consider different seeding and accretion scenarios4–7, which require the detection and characterization of black holes in the first few hundred million years after the Big Bang to be validated. Here we present an extensive analysis of the JWST-NIRSpec spectrum of GN-z11, an exceptionally luminous galaxy at z = 10.6, revealing the detection of the [Neiv]λ2423 and CII*λ1335 transitions (typical of active galactic nuclei), as well as semi-forbidden nebular lines tracing gas densities higher than 109 cm−3, typical of the broad line region of active galactic nuclei. These spectral features indicate that GN-z11 hosts an accreting black hole. The spectrum also reveals a deep and blueshifted CIVλ1549 absorption trough, tracing an outflow with velocity 800−1,000 km s−1, probably driven by the active galactic nucleus. Assuming local virial relations, we derive a black hole mass of log(MBH/M⊙)=6.2±0.3, accreting at about five times the Eddington rate. These properties are consistent with both heavy seeds scenarios and scenarios considering intermediate and light seeds experiencing episodic super-Eddington phases. Our finding explains the high luminosity of GN-z11 and can also provide an explanation for its exceptionally high nitrogen abundance

Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target

Reverse transcription is the central defining feature of HIV-1 replication. We previously reported that the cellular eukaryotic elongation factor 1 (eEF1) complex associates with the HIV-1 reverse transcription complex (RTC) and the association is important for late steps of reverse transcription. Here we show that associationbetween the eEF1 and RTC complexes occurs by a strong and direct interaction between the subunit eEF1A and reverse transcriptase (RT). Using biolayer interferometry and co-immunoprecipitation (co-IP) assays, we show that association between the eEF1 and RTC complexes occurs by a strong (KD ~3–4 nM) and direct interaction between eEF1A and reverse transcriptase (RT). Biolayer interferometry analysis of cell lysates with titrated levels of eEF1A indicates it is a predominant cellular RT binding protein. Both the RT thumb and connection domains are required for interaction with eEF1A. A single amino acid mutation, W252A, within the thumb domain impaired co-IP between eEF1A and RT, and also significantly reduced the efficiency of late reverse transcription and virus replication when incorporated into infectious HIV-1. Molecular modeling analysis indicated that interaction between W252 and L303 are important for RT structure, and their mutation to alanine did not impair heterodimerisation, but negatively impacted interaction with eEF1A. Didemnin B, which specifically binds eEF1A, potently inhibited HIV-1 reverse transcription by greater than 2 logs at subnanomolar concentrations, especially affecting reverse transcription late DNA synthesis. Analysis showed reduced levels of RTCs from HIV-1-infected HEK293T treated with didemnin B compared to untreated cells. Interestingly, HIV-1 with a W252A RT mutation was resistant to didemnin B negative effects showing that didemnin B affects HIV-1 by targeting the RT-eEF1A interaction. The combined evidence indicates a direct interaction between eEF1A and RT is crucial for HIV reverse transcription and replication, and the RT-eEF1A interaction is a potential drug target

JADES. The diverse population of infant Black Holes at 4<z<11: merging, tiny, poor, but mighty

We present 12 new AGN at 4<z<7 in the JADES survey (in addition to the previously identified AGN in GN-z11 at z=10.6) revealed through the detection of a Broad Line Region as seen in the Balmer emission lines. The depth of JADES, together with the use of three different spectral resolutions, enables us to probe a lower mass regime relative to previous studies. In a few cases we find evidence for two broad components of Halpha which suggests that these could be candidate merging black holes (BHs). The inferred BH masses range between 8 x 10^7 Msun down to 4 x 10^5 Msun, interestingly probing the regime expected for Direct Collapse Black Holes. The inferred AGN bolometric luminosities (~10^44-10^45 erg/s) imply accretion rates that are < 0.5 times the Eddington rate in most cases. However, small BH, with M_BH ~ 10^6 Msun, tend to accrete at Eddington or super-Eddington rates. These BH at z~4-11 are over-massive relative to their host galaxies stellar masses when compared to the local M_BH-Mstar relation. However, we find that these early BH tend to be more consistent with the local relation between M_BH and velocity dispersion, as well as between M_BH and dynamical mass, suggesting that these are more fundamental and universal relations. On the BPT excitation-diagnostic diagram these AGN are located in the region that is that is locally occupied by star-forming galaxies, implying that they would be missed by the standard classification techniques if they did not display broad lines. Their location on the diagram is consistent with what expected for AGN hosted in metal poor galaxies (Z ~ 0.1-0.2 Zsun). The fraction of broad line AGN with L_AGN > 10^44 erg/s, among galaxies in the redshift range 4<z<6, is about 10%, suggesting that the contribution of AGN and their hosts to the reionization of the Universe is > 10%.Comment: Submitted to A&A, 25 pages, 13 figures, 4 table

The Cosmos in its Infancy: JADES Galaxy Candidates at z > 8 in GOODS-S and GOODS-N

We present a catalog of 717 candidate galaxies at $z > 8$ selected from 125 square arcminutes of NIRCam imaging as part of the JWST Advanced Deep Extragalactic Survey (JADES). We combine the full JADES imaging dataset with data from the JEMS and FRESCO JWST surveys along with extremely deep existing observations from HST/ACS for a final filter set that includes fifteen JWST/NIRCam filters and five HST/ACS filters. The high-redshift galaxy candidates were selected from their estimated photometric redshifts calculated using a template fitting approach, followed by visual inspection from seven independent reviewers. We explore these candidates in detail, highlighting interesting resolved or extended sources, sources with very red long-wavelength slopes, and our highest redshift candidates, which extend to $z_{phot} = 18$. We also investigate potential contamination by stellar objects, and do not find strong evidence from SED fitting that these faint high-redshift galaxy candidates are low-mass stars. Over 93\% of the sources are newly identified from our deep JADES imaging, including 31 new galaxy candidates at $z_{phot} > 12$. Using 42 sources in our sample with measured spectroscopic redshifts from NIRSpec and FRESCO, we find excellent agreement to our photometric redshift estimates, with no catastrophic outliers and an average difference of $\langle \Delta z = z_{phot}- z_{spec} \rangle= 0.26$. These sources comprise one of the most robust samples for probing the early buildup of galaxies within the first few hundred million years of the Universe's history.Comment: v2: 40 pages, 18 figures, submitted to AAS Journals, online data catalog (JADES Deep only) found at https://doi.org/10.5281/zenodo.809252

JADES: Detecting [OIII]λ4363λ4363 Emitters and Testing Strong Line Calibrations in the High-zz Universe with Ultra-deep JWST/NIRSpec Spectroscopy up to z∼9.5z \sim 9.5

© 2024 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/We present ten novel [OIII]λ4363 auroral line detections up to z ∼ 9.5 measured from ultra-deep JWST/NIRSpec MSA spectroscopy from the JWST Advanced Deep Extragalactic Survey (JADES). We leverage the deepest spectroscopic observations taken thus far with NIRSpec to determine electron temperatures and oxygen abundances using the direct Te method. We directly compare these results against a suite of locally calibrated strong-line diagnostics and recent high-z calibrations. We find the calibrations fail to simultaneously match our JADES sample, thus warranting a self-consistent revision of these calibrations for the high-z Universe. We find a weak dependence between R2 and O3O2 with metallicity, thus suggesting these line ratios are inefficient in the high-z Universe as metallicity diagnostics and degeneracy breakers. We find R3 and R23 are still correlated with metallicity, but we find a tentative flattening of these diagnostics, thus suggesting future difficulties when applying these strong line ratios as metallicity indicators in the high-z Universe. We also propose and test an alternative diagnostic based on a different combination of R3 and R2 with a higher dynamic range. We find a reasonably good agreement (median offset of 0.002 dex, median absolute offset of 0.13 dex) with the JWST sample at low metallicity, but future investigations are required on larger samples to probe past the turnover point. At a given metallicity, our sample demonstrates higher ionization and excitation ratios than local galaxies with rest-frame EWs(Hβ) ≈200 − 300 Å. However, we find the median rest-frame EWs(Hβ) of our sample to be ∼2× less than the galaxies used for the local calibrations. This EW discrepancy combined with the high ionization of our galaxies does not offer a clear description of [OIII]λ4363 production in the high-z Universe, thus warranting a much deeper examination into the factors influencing these processes.Peer reviewe

The Cosmos in its Infancy: JADES Galaxy Candidates at z > 8 in GOODS-S and GOODS-N

© 2024. The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/We present a catalog of 717 candidate galaxies at z > 8 selected from 125 square arcmin of NIRCam imaging as part of the JWST Advanced Deep Extragalactic Survey (JADES). We combine the full JADES imaging data set with data from the JWST Extragalactic Medium Survey and First Reionization Epoch Spectroscopic COmplete Survey (FRESCO) along with extremely deep existing observations from Hubble Space Telescope (HST)/Advanced Camera for Surveys (ACS) for a final filter set that includes 15 JWST/NIRCam filters and five HST/ACS filters. The high-redshift galaxy candidates were selected from their estimated photometric redshifts calculated using a template-fitting approach, followed by visual inspection from seven independent reviewers. We explore these candidates in detail, highlighting interesting resolved or extended sources, sources with very red long-wavelength slopes, and our highest-redshift candidates, which extend to z phot ∼ 18. Over 93% of the sources are newly identified from our deep JADES imaging, including 31 new galaxy candidates at z phot > 12. We also investigate potential contamination by stellar objects, and do not find strong evidence from spectral energy distribution fitting that these faint high-redshift galaxy candidates are low-mass stars. Using 42 sources in our sample with measured spectroscopic redshifts from NIRSpec and FRESCO, we find excellent agreement to our photometric redshift estimates, with no catastrophic outliers and an average difference of 〈Δz = z phot − z spec〉 = 0.26. These sources comprise one of the most robust samples for probing the early buildup of galaxies within the first few hundred million years of the Universe’s history.Peer reviewe